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Segmental overgrowth disorders - Deep sequencing v3.7 GJA4 Arina Puzriakova gene: GJA4 was added
gene: GJA4 was added to Segmental overgrowth disorders - Deep sequencing. Sources: Expert Review Amber,Expert list
Q3_23_promote_green, Q3_23_NHS_review, recurrent-variant tags were added to gene: GJA4.
Mode of inheritance for gene: GJA4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GJA4 were set to 33912852; 35642047; 35902510; 36209871; 37072338
Phenotypes for gene: GJA4 were set to Cutaneous and hepatic vascular lesions (no OMIM phenotype)
Penetrance for gene: GJA4 were set to unknown
Mode of pathogenicity for gene: GJA4 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Mosaic skin disorders - Deep sequencing v2.14 GJA4 Arina Puzriakova Publications for gene: GJA4 were set to 33912852
Dystonia, chorea or related movement disorder, adult onset v3.7 ATXN1_CAG Eleanor Williams commented on STR: ATXN1_CAG
Dystonia, chorea or related movement disorder, adult onset v3.7 ATXN1_CAG Eleanor Williams Classified STR: ATXN1_CAG as Green List (high evidence)
Dystonia, chorea or related movement disorder, adult onset v3.7 ATXN1_CAG Eleanor Williams Str: atxn1_cag has been classified as Green List (High Evidence).
Dystonia, chorea or related movement disorder, adult onset v3.6 ATXN1_CAG Eleanor Williams Tag watchlist was removed from STR: ATXN1_CAG.
Tag Q3_23_promote_green was removed from STR: ATXN1_CAG.
Mosaic skin disorders - Deep sequencing v2.13 GJA4 Arina Puzriakova Classified gene: GJA4 as Amber List (moderate evidence)
Mosaic skin disorders - Deep sequencing v2.13 GJA4 Arina Puzriakova Added comment: Comment on list classification: New gene added by Tom Cullup (GOSH). There is sufficient evidence to promote this gene to green at the next GMS panel update.

A recurrent GJA4 c.121G>T (p.Gly41Cys) somatic variant has been found in >50 individuals with cavernous venous malformation. The same somatic variant has been found in at least three unrelated cases with cutaneous lesions which plausibly could be referred via this panel. Functional studies have shown this is a GoF variant that leads to formation of a hyperactive hemichannel.
Mosaic skin disorders - Deep sequencing v2.13 GJA4 Arina Puzriakova Gene: gja4 has been classified as Amber List (Moderate Evidence).
Mosaic skin disorders - Deep sequencing v2.12 GJA4 Arina Puzriakova Tag Q3_23_promote_green tag was added to gene: GJA4.
Tag Q3_23_NHS_review tag was added to gene: GJA4.
Tag recurrent-variant tag was added to gene: GJA4.
Hereditary neuropathy or pain disorder v3.45 AGTPBP1 Achchuthan Shanmugasundram Classified gene: AGTPBP1 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v3.45 AGTPBP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to green rating at the next major review.
Hereditary neuropathy or pain disorder v3.45 AGTPBP1 Achchuthan Shanmugasundram Gene: agtpbp1 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v3.44 AGTPBP1 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: AGTPBP1.
Hereditary neuropathy or pain disorder v3.44 AGTPBP1 Achchuthan Shanmugasundram reviewed gene: AGTPBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30420557; Phenotypes: Neurodegeneration, childhood-onset, with cerebellar atrophy, OMIM:618276; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.223 ZNF292 Achchuthan Shanmugasundram reviewed gene: ZNF292: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal dominant 64, OMIM:619188; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v4.75 PIP5K1C Achchuthan Shanmugasundram Classified gene: PIP5K1C as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.75 PIP5K1C Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (seven unrelated cases and supporting functional evidence) for promoting this gene to green rating in the next GMS review.
Early onset or syndromic epilepsy v4.75 PIP5K1C Achchuthan Shanmugasundram Gene: pip5k1c has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.74 PIP5K1C Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: PIP5K1C.
Early onset or syndromic epilepsy v4.74 PIP5K1C Achchuthan Shanmugasundram Phenotypes for gene: PIP5K1C were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; epilepsy, MONDO:0005027
Early onset or syndromic epilepsy v4.73 PIP5K1C Achchuthan Shanmugasundram edited their review of gene: PIP5K1C: Changed phenotypes to: neurodevelopmental disorder, MONDO:0700092, epilepsy, MONDO:0005027
Intellectual disability v5.223 PIP5K1C Achchuthan Shanmugasundram Classified gene: PIP5K1C as Amber List (moderate evidence)
Intellectual disability v5.223 PIP5K1C Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (nine unrelated cases and supporting functional evidence) for promoting this gene to green rating in the next GMS review.
Intellectual disability v5.223 PIP5K1C Achchuthan Shanmugasundram Gene: pip5k1c has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.222 PIP5K1C Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: PIP5K1C.
Early onset or syndromic epilepsy v4.73 PIP5K1C Achchuthan Shanmugasundram gene: PIP5K1C was added
gene: PIP5K1C was added to Early onset or syndromic epilepsy. Sources: Literature
Mode of inheritance for gene: PIP5K1C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PIP5K1C were set to 37451268
Phenotypes for gene: PIP5K1C were set to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Review for gene: PIP5K1C was set to GREEN
Added comment: Three de novo heterozygous missense variants in PIP5K1C (p.Glu146Lys, p.Tyr205Cys & p.Tyr221Cys) were identified in nine unrelated children exhibiting intellectual disability, developmental delay, acquired microcephaly, seizures, visual abnormalities, and dysmorphic features. Intellectual disability was reported in all nine children and seizures were present in seven children, of which three had developmental and epileptic encephalopathy. In addition, there is functional evidence available, which includes an in vivo zebrafish model that recapitulates the human phenotype (developmental defects affecting the forebrain, including the eyes, as well as craniofacial abnormalities) (PMID:37451268).

This gene has been associated with another phenotype (Lethal congenital contractural syndrome 3, MIM #611369) in both OMIM and Gene2Phenotype, but not yet associated with this neurodevelopmental disorders in either databases.
Sources: Literature
Intellectual disability v5.222 PIP5K1C Achchuthan Shanmugasundram gene: PIP5K1C was added
gene: PIP5K1C was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: PIP5K1C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PIP5K1C were set to 37451268
Phenotypes for gene: PIP5K1C were set to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Review for gene: PIP5K1C was set to GREEN
Added comment: Three de novo heterozygous missense variants in PIP5K1C (p.Glu146Lys, p.Tyr205Cys & p.Tyr221Cys) were identified in nine unrelated children exhibiting intellectual disability, developmental delay, acquired microcephaly, seizures, visual abnormalities, and dysmorphic features. Intellectual disability was reported in all nine children and seizures were present in seven children, of which three had developmental and epileptic encephalopathy. In addition, there is functional evidence available, which includes an in vivo zebrafish model that recapitulates the human phenotype (developmental defects affecting the forebrain, including the eyes, as well as craniofacial abnormalities) (PMID:37451268).

This gene has been associated with another phenotype (Lethal congenital contractural syndrome 3, MIM #611369) in both OMIM and Gene2Phenotype, but not yet associated with this neurodevelopmental disorders in either databases.
Sources: Literature
Mosaic skin disorders - Deep sequencing v2.12 FGFR2 Arina Puzriakova Tag somatic tag was added to gene: FGFR2.
Mosaic skin disorders - Deep sequencing v2.12 FGFR2 Arina Puzriakova Publications for gene: FGFR2 were set to 9728990
Mosaic skin disorders - Deep sequencing v2.11 FGFR2 Arina Puzriakova Mode of pathogenicity for gene: FGFR2 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Mosaic skin disorders - Deep sequencing v2.10 FGFR2 Arina Puzriakova Classified gene: FGFR2 as Amber List (moderate evidence)
Mosaic skin disorders - Deep sequencing v2.10 FGFR2 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to green at the next GMS panel update. FGFR2 is associated with multiple phenotypes but mosaic somatic variants have been found in more than 10 unrelated individuals in literature with nevoid skin disorders.
Mosaic skin disorders - Deep sequencing v2.10 FGFR2 Arina Puzriakova Gene: fgfr2 has been classified as Amber List (Moderate Evidence).
Possible mitochondrial disorder, nuclear genes v3.33 LETM1 Carl Fratter gene: LETM1 was added
gene: LETM1 was added to Possible mitochondrial disorder - nuclear genes. Sources: Expert Review
Mode of inheritance for gene: LETM1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: LETM1 were set to 620089 Neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction
Review for gene: LETM1 was set to GREEN
Added comment: Consensus opinion from the 3 NHSE GMS specialist mitochondrial providers.
Sources: Expert Review
Mosaic skin disorders - Deep sequencing v2.9 FGFR2 Arina Puzriakova Tag Q3_23_promote_green tag was added to gene: FGFR2.
Tag Q3_23_NHS_review tag was added to gene: FGFR2.
Paediatric or syndromic cardiomyopathy v3.20 NAA10 Achchuthan Shanmugasundram Classified gene: NAA10 as Amber List (moderate evidence)
Paediatric or syndromic cardiomyopathy v3.20 NAA10 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are two unrelated cases with paediatric-onset hypertrophic cardiomyopathy. Hence, this gene should be rated amber.
Paediatric or syndromic cardiomyopathy v3.20 NAA10 Achchuthan Shanmugasundram Gene: naa10 has been classified as Amber List (Moderate Evidence).
Paediatric or syndromic cardiomyopathy v3.19 NAA10 Achchuthan Shanmugasundram gene: NAA10 was added
gene: NAA10 was added to Paediatric or syndromic cardiomyopathy. Sources: Literature
Mode of inheritance for gene: NAA10 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: NAA10 were set to 29748569
Phenotypes for gene: NAA10 were set to Ogden syndrome, OMIM:300855
Review for gene: NAA10 was set to AMBER
Added comment: PMID:29748569 reported the identification of previously undescribed NAA10 variant (c.215T>C; p.Ile72Thr) in three boys from two unrelated families with a milder phenotypic spectrum in comparison to most of the previously described patients with NAA10 variants. These boys had developmental delay, intellectual disability, and hypertrophic cardiomyopathy.

This gene has been associated with Ogden syndrome in both OMIM ands Gene2Phenotype and the OMIM record includes hypertrophic cardiomyopathy and other cardiac abnormalities as clinical manifestations of this disorder.
Sources: Literature
Possible mitochondrial disorder, nuclear genes v3.33 IDH3A Carl Fratter edited their review of gene: IDH3A: Added comment: Consensus opinion from the 3 specialist mitochondrial providers.; Changed publications to: 28412069, 28058510, 30478029; Changed phenotypes to: Infantile encephalopathy, 619007 Retinitis pigmentosa 90
Possible mitochondrial disorder, nuclear genes v3.33 CRLS1 Carl Fratter reviewed gene: CRLS1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: 620167 Combined oxidative phosphorylation deficiency 57; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Possible mitochondrial disorder, nuclear genes v3.33 C2orf69 Carl Fratter reviewed gene: C2orf69: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: 619423 Combined oxidative phosphorylation deficiency 53; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Possible mitochondrial disorder, nuclear genes v3.33 ATP5O Carl Fratter edited their review of gene: ATP5O: Added comment: Consensus opinion from the 3 specialist mitochondrial providers.; Changed rating: GREEN; Changed phenotypes to: 620359 Mitochondrial complex V (ATP synthase) deficiency, nuclear type 7; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric or syndromic cardiomyopathy v3.18 NAA15 Achchuthan Shanmugasundram Publications for gene: NAA15 were set to
Paediatric or syndromic cardiomyopathy v3.17 NAA15 Achchuthan Shanmugasundram Phenotypes for gene: NAA15 were changed from to hypertrophic cardiomyopathy, MONDO:0005045
Paediatric or syndromic cardiomyopathy v3.16 NAA15 Achchuthan Shanmugasundram Mode of inheritance for gene: NAA15 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Paediatric or syndromic cardiomyopathy v3.15 NAA15 Achchuthan Shanmugasundram changed review comment from: PMID:33103328 reported two unrelated individuals with paediatric hypertrophic cardiomyopathy and they were identified with de novo variants in NAA15 gene (patient 1: c.1009_1012delGAAA/ p.Glu337fs, patient 2: c.79A>G/ p.Arg27Gly). These patients presented with cardiomyopathy at 2 months and 6 years of age respectively.

Although none of the patients reported with hypertrophic cardiomyopathy in PMID:29656860, 4 of 19 patients were reported with congenital cardiac defects.

Although this gene has not yet been associated with cardiac abnormalities in OMIM, this gene has been associated with "Congenital heart disease and neurodevelopmental disorder" in the DD panel of Gene2Phenotype database (with 'strong' rating).; to: Comment on gene rating: The rating of this gene should remain amber in this panel, as there are only two unrelated c cases reported with paediatric hypertrophic cardiomyopathy.

PMID:33103328 reported two unrelated individuals with paediatric hypertrophic cardiomyopathy and they were identified with de novo variants in NAA15 gene (patient 1: c.1009_1012delGAAA/ p.Glu337fs, patient 2: c.79A>G/ p.Arg27Gly). These patients presented with cardiomyopathy at 2 months and 6 years of age respectively.

Although none of the patients reported with hypertrophic cardiomyopathy in PMID:29656860, 4 of 19 patients were reported with congenital cardiac defects.

Although this gene has not yet been associated with cardiac abnormalities in OMIM, this gene has been associated with "Congenital heart disease and neurodevelopmental disorder" in the DD panel of Gene2Phenotype database (with 'strong' rating).
Paediatric or syndromic cardiomyopathy v3.15 NAA15 Achchuthan Shanmugasundram reviewed gene: NAA15: Rating: AMBER; Mode of pathogenicity: None; Publications: 33103328; Phenotypes: hypertrophic cardiomyopathy, MONDO:0005045; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Retinal disorders v4.20 MPDZ Siying Lin changed review comment from: PMID 28556411: 3 families with affected individuals with biallelic MPDZ variants and congenital hydrocephalus with retinohoroidal coloboma, macular hypoplasia and foveal hypoplasia
PMID 36594712: 2 siblings with biallelic MPDZ variants and macular colobomas
PMID 36429029: proband with biallelic MPDZ variants and macular coloboma
Sources: Literature; to: PMID 28556411: 3 families with affected individuals with biallelic MPDZ variants and congenital hydrocephalus with retinohoroidal coloboma, macular hypoplasia and foveal hypoplasia
PMID 36594712: 2 siblings with biallelic MPDZ variants and macular colobomas
PMID 36429029: proband with biallelic MPDZ variants and macular coloboma
Sources: Literature
Retinal disorders v4.20 MPDZ Siying Lin gene: MPDZ was added
gene: MPDZ was added to Retinal disorders. Sources: Literature
Mode of inheritance for gene: MPDZ was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MPDZ were set to PMID 28556411, 36594712, 36429029
Mode of pathogenicity for gene: MPDZ was set to Other
Added comment: PMID 28556411: 3 families with affected individuals with biallelic MPDZ variants and congenital hydrocephalus with retinohoroidal coloboma, macular hypoplasia and foveal hypoplasia
PMID 36594712: 2 siblings with biallelic MPDZ variants and macular colobomas
PMID 36429029: proband with biallelic MPDZ variants and macular coloboma
Sources: Literature
Early onset or syndromic epilepsy v4.72 TMEM63B Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient evidence available (17 unrelated cases) in support of promoting this gene to green rating in the next GMS review; to: Comment on list classification: There is sufficient evidence available (17 unrelated cases) in support of promoting this gene to green rating in the next GMS review.
Early onset or syndromic epilepsy v4.72 TMEM63B Achchuthan Shanmugasundram Classified gene: TMEM63B as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.72 TMEM63B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (17 unrelated cases) in support of promoting this gene to green rating in the next GMS review
Early onset or syndromic epilepsy v4.72 TMEM63B Achchuthan Shanmugasundram Gene: tmem63b has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.71 TMEM63B Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: TMEM63B.
Early onset or syndromic epilepsy v4.71 TMEM63B Achchuthan Shanmugasundram changed review comment from: PMID:37421948 - 17 unrelated individuals with severe early-onset developmental and epileptic encephalopathy (DEE), intellectual disability, and severe motor and cortical visual impairment were identified with ten distinct heterozygous variants inTMEM63B. The variants occurred de novo in 16/17 individuals for whom parental DNA was available and either missense or in-frame. All individuals had global developmental delay, with moderate-to-profound intellectual disability and severe motor impairment.
Sources: Literature; to: PMID:37421948 - 17 unrelated individuals with severe early-onset developmental and epileptic encephalopathy (DEE), intellectual disability, and severe motor and cortical visual impairment were identified with ten distinct heterozygous variants inTMEM63B. The variants occurred de novo in 16/17 individuals for whom parental DNA was available and either missense or in-frame. All individuals had early-onset drug-resistant epilepsy, whose onset ranged from birth to 3 years but occurred within the first year in 14/17 (82%) and in the first month of life in 6/17 (35%).
Sources: Literature
Intellectual disability v5.221 TMEM63B Achchuthan Shanmugasundram Classified gene: TMEM63B as Amber List (moderate evidence)
Intellectual disability v5.221 TMEM63B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (17 unrelated cases) in support of promoting this gene to green rating in the next GMS review.
Intellectual disability v5.221 TMEM63B Achchuthan Shanmugasundram Gene: tmem63b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.220 TMEM63B Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: TMEM63B.
Early onset or syndromic epilepsy v4.71 TMEM63B Achchuthan Shanmugasundram gene: TMEM63B was added
gene: TMEM63B was added to Early onset or syndromic epilepsy. Sources: Literature
Mode of inheritance for gene: TMEM63B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TMEM63B were set to 37421948
Phenotypes for gene: TMEM63B were set to developmental and epileptic encephalopathy, MONDO:0100062
Review for gene: TMEM63B was set to GREEN
Added comment: PMID:37421948 - 17 unrelated individuals with severe early-onset developmental and epileptic encephalopathy (DEE), intellectual disability, and severe motor and cortical visual impairment were identified with ten distinct heterozygous variants inTMEM63B. The variants occurred de novo in 16/17 individuals for whom parental DNA was available and either missense or in-frame. All individuals had global developmental delay, with moderate-to-profound intellectual disability and severe motor impairment.
Sources: Literature
Intellectual disability v5.220 TMEM63B Achchuthan Shanmugasundram gene: TMEM63B was added
gene: TMEM63B was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: TMEM63B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TMEM63B were set to 37421948
Phenotypes for gene: TMEM63B were set to developmental and epileptic encephalopathy, MONDO:0100062
Review for gene: TMEM63B was set to GREEN
Added comment: PMID:37421948 - 17 unrelated individuals with severe early-onset developmental and epileptic encephalopathy (DEE), intellectual disability, and severe motor and cortical visual impairment were identified with ten distinct heterozygous variants inTMEM63B. The variants occurred de novo in 16/17 individuals for whom parental DNA was available and either missense or in-frame. All individuals had global developmental delay, with moderate-to-profound intellectual disability and severe motor impairment.
Sources: Literature
Intellectual disability v5.219 DHX9 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.219 DHX9 Achchuthan Shanmugasundram Classified gene: DHX9 as Amber List (moderate evidence)
Intellectual disability v5.219 DHX9 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (eight unrelated cases) in support of promoting this gene to green rating at the next GMS review.
Intellectual disability v5.219 DHX9 Achchuthan Shanmugasundram Gene: dhx9 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.219 DHX9 Achchuthan Shanmugasundram Classified gene: DHX9 as Amber List (moderate evidence)
Intellectual disability v5.219 DHX9 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (eight unrelated cases) in support of promoting this gene to green rating at the next GMS review.
Intellectual disability v5.219 DHX9 Achchuthan Shanmugasundram Gene: dhx9 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.218 DHX9 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: DHX9.
Intellectual disability v5.218 DHX9 Achchuthan Shanmugasundram gene: DHX9 was added
gene: DHX9 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: DHX9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DHX9 were set to 37467750
Phenotypes for gene: DHX9 were set to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Review for gene: DHX9 was set to GREEN
Added comment: PMID:37467750 - 17 unrelated individuals were identified with de novo, ultra-rare, heterozygous missense or loss-of-function DHX9 variants, of which 14 individuals were reported with a neurodevelopmental disorder (NDD) and three were reported with Charcot-Marie-Tooth disease (CMT). All 14 cases with NDD had developmental delay, of which eight were reported with intellectual disability (4 severe, 1 moderate, 3 mild). Two cases did not have ID, one had borderline ID and three cases were too young (0-5 years old).
Sources: Literature
Hereditary neuropathy or pain disorder v3.44 DHX9 Achchuthan Shanmugasundram Classified gene: DHX9 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v3.44 DHX9 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (three unrelated cases) for promoting this gene to green rating in the next major update.
Hereditary neuropathy or pain disorder v3.44 DHX9 Achchuthan Shanmugasundram Gene: dhx9 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v3.43 DHX9 Achchuthan Shanmugasundram Tag watchlist was removed from gene: DHX9.
Tag Q3_23_promote_green tag was added to gene: DHX9.
Hereditary neuropathy or pain disorder v3.43 DHX9 Achchuthan Shanmugasundram Phenotypes for gene: DHX9 were changed from Adult-onset axonal neuropathy to Adult-onset axonal neuropathy; Charcot-Marie-Tooth disease, MONDO:0015626
Hereditary neuropathy or pain disorder v3.42 DHX9 Achchuthan Shanmugasundram Publications for gene: DHX9 were set to
Hereditary neuropathy or pain disorder v3.41 DHX9 Achchuthan Shanmugasundram Mode of inheritance for gene: DHX9 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v3.40 DHX9 Achchuthan Shanmugasundram reviewed gene: DHX9: Rating: GREEN; Mode of pathogenicity: None; Publications: 37467750; Phenotypes: Charcot-Marie-Tooth disease, MONDO:0015626; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia and cerebellar anomalies - childhood onset v4.24 DNAJC3 Achchuthan Shanmugasundram Classified gene: DNAJC3 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - childhood onset v4.24 DNAJC3 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are five unrelated families identified with biallelic DNAJC3 variants and reported with gait ataxia since childhood/ adolescence. Hence, this gene can be promoted to Green rating in the next GMS update.
Ataxia and cerebellar anomalies - childhood onset v4.24 DNAJC3 Achchuthan Shanmugasundram Gene: dnajc3 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - childhood onset v4.23 DNAJC3 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: DNAJC3.
Ataxia and cerebellar anomalies - childhood onset v4.23 DNAJC3 Achchuthan Shanmugasundram gene: DNAJC3 was added
gene: DNAJC3 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: DNAJC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAJC3 were set to 25466870; 28940199; 32738013; 33486469; 34654017
Phenotypes for gene: DNAJC3 were set to Ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus, OMIM:616192
Review for gene: DNAJC3 was set to GREEN
Added comment: PMID:25466870 - Five individuals from two different families were identified with homozygous DNAJC3 variants (family 1: c.580C>T (p.Arg194Ter); family 2: 72kb del (exons 6-12)) and reported with gait ataxia as one of the clinical manifestations. The onset of gait disturbances was during childhood/ adolescence for four of these cases.

PMID:28940199 - Cousin of family 1 from PMID:2546687 with the same variant and presented with gait ataxia since 15 years of age.

PMID:32738013 - Two unrelated children were identified with homozygous splice site variants (case 1: c.393+2T>G; case 2: c.393+2T>C) in DNAJC3 and were reported with gait ataxia.

PMID:33486469 - Two unrelated patients were identified with compound heterozygous (patient 1: p.Met1Val & p.Arg346Ter) or homozygous (patient 2: p.Arg393Ter) variants, of which patient 1 had ataxia.

PMID:34654017 - Two siblings (aged 10 and 5 years) identified with homozygous DNAJC3 variant (c.367_1370delAGAA; p.Lys456SerfsTer85) presented with gait ataxia.
Sources: Literature
Hereditary neuropathy v1.472 DNAJC3 Achchuthan Shanmugasundram changed review comment from: PMID:25466870 - Five individuals from two different families with demyelinating sensorimotor peripheral neuropathy and identified with homozygous DNAJC3 variants (family 1: c.580C>T (p.Arg194Ter); family 2: 72kb del (exons 6-12)).

PMID:28940199 - Cousin of family 1 from PMID:2546687 with the same variant and presented with demyelinating sensorimotor peripheral neuropathy.

PMID:32738013 - Two unrelated cases with homozygous splice site variants (case 1: c.393+2T>G; case 2: c.393+2T>C) in DNAJC3 and were reported with sensorimotor demyelinating and axonal polyneuropathy among several clinical manifestations.

PMID:33486469 - Two unrelated patients identified with compound heterozygous (patient 1: p.Met1Val & p.Arg346Ter) or homozygous (p.Arg393Ter) variants, of which patient 1 had demyelinating peripheral sensorimotor neuropathy.

PMID:34654017 - One of two siblings identified with homozygous DNAJC3 variant (c.367_1370delAGAA; p.Lys456SerfsTer85) presented with demyelinating neuropathy among several other clinical manifestations.; to: PMID:25466870 - Five individuals from two different families with demyelinating sensorimotor peripheral neuropathy and identified with homozygous DNAJC3 variants (family 1: c.580C>T (p.Arg194Ter); family 2: 72kb del (exons 6-12)).

PMID:28940199 - Cousin of family 1 from PMID:2546687 with the same variant and presented with demyelinating sensorimotor peripheral neuropathy.

PMID:32738013 - Two unrelated cases with homozygous splice site variants (case 1: c.393+2T>G; case 2: c.393+2T>C) in DNAJC3 and were reported with sensorimotor demyelinating and axonal polyneuropathy.

PMID:33486469 - Two unrelated patients identified with compound heterozygous (patient 1: p.Met1Val & p.Arg346Ter) or homozygous (p.Arg393Ter) variants, of which patient 1 had demyelinating peripheral sensorimotor neuropathy.

PMID:34654017 - One of two siblings identified with homozygous DNAJC3 variant (c.367_1370delAGAA; p.Lys456SerfsTer85) presented with demyelinating neuropathy.
Monogenic hearing loss v4.12 DNAJC3 Achchuthan Shanmugasundram Classified gene: DNAJC3 as Amber List (moderate evidence)
Monogenic hearing loss v4.12 DNAJC3 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are seven unrelated families with DNAJC3 biallelic variants and presenting with sensorineural hearing loss. Hence, this gene can be promoted to Green at the next GMS review.
Monogenic hearing loss v4.12 DNAJC3 Achchuthan Shanmugasundram Gene: dnajc3 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v4.11 DNAJC3 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: DNAJC3.
Monogenic hearing loss v4.11 DNAJC3 Achchuthan Shanmugasundram changed review comment from: PMID:25466870 - Five individuals from two different families were identified with homozygous DNAJC3 variants (family 1: c.580C>T (p.Arg194Ter); family 2: 72kb del (exons 6-12)), of which all three individuals from family 1 and one of two individuals from family 2 were reported with sensorineural hearing loss among several clinical manifestations.

PMID:28940199 - Cousin of family 1 from PMID:2546687 with the same variant and presented with sensorineural hearing loss.

PMID:32738013 - Two unrelated cases with homozygous splice site variants (case 1: c.393+2T>G; case 2: c.393+2T>C) in DNAJC3 and were reported with sensorineural hearing loss.

PMID:33486469 - Two unrelated patients identified with compound heterozygous (patient 1: p.Met1Val & p.Arg346Ter) or homozygous (p.Arg393Ter) variants, and both had sensorineural hearing loss.

PMID:34654017 - Ttwo siblings identified with homozygous DNAJC3 variant (c.367_1370delAGAA; p.Lys456SerfsTer85) presented with sensorineural hearing loss.
Sources: Literature; to: PMID:25466870 - Five individuals from two different families were identified with homozygous DNAJC3 variants (family 1: c.580C>T (p.Arg194Ter); family 2: 72kb del (exons 6-12)), of which all three individuals from family 1 and one of two individuals from family 2 were reported with sensorineural hearing loss among several clinical manifestations.

PMID:28940199 - Cousin of family 1 from PMID:2546687 with the same variant and presented with sensorineural hearing loss.

PMID:32738013 - Two unrelated cases with homozygous splice site variants (case 1: c.393+2T>G; case 2: c.393+2T>C) in DNAJC3 and were reported with sensorineural hearing loss.

PMID:33486469 - Two unrelated patients identified with compound heterozygous (patient 1: p.Met1Val & p.Arg346Ter) or homozygous (p.Arg393Ter) variants, and both had sensorineural hearing loss.

PMID:34654017 - Two siblings identified with homozygous DNAJC3 variant (c.367_1370delAGAA; p.Lys456SerfsTer85) presented with sensorineural hearing loss.
Sources: Literature
Monogenic hearing loss v4.11 DNAJC3 Achchuthan Shanmugasundram gene: DNAJC3 was added
gene: DNAJC3 was added to Monogenic hearing loss. Sources: Literature
Mode of inheritance for gene: DNAJC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAJC3 were set to 25466870; 28940199; 32738013; 33486469; 34654017
Phenotypes for gene: DNAJC3 were set to Ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus, OMIM:616192
Review for gene: DNAJC3 was set to GREEN
Added comment: PMID:25466870 - Five individuals from two different families were identified with homozygous DNAJC3 variants (family 1: c.580C>T (p.Arg194Ter); family 2: 72kb del (exons 6-12)), of which all three individuals from family 1 and one of two individuals from family 2 were reported with sensorineural hearing loss among several clinical manifestations.

PMID:28940199 - Cousin of family 1 from PMID:2546687 with the same variant and presented with sensorineural hearing loss.

PMID:32738013 - Two unrelated cases with homozygous splice site variants (case 1: c.393+2T>G; case 2: c.393+2T>C) in DNAJC3 and were reported with sensorineural hearing loss.

PMID:33486469 - Two unrelated patients identified with compound heterozygous (patient 1: p.Met1Val & p.Arg346Ter) or homozygous (p.Arg393Ter) variants, and both had sensorineural hearing loss.

PMID:34654017 - Ttwo siblings identified with homozygous DNAJC3 variant (c.367_1370delAGAA; p.Lys456SerfsTer85) presented with sensorineural hearing loss.
Sources: Literature
Hereditary neuropathy or pain disorder v3.40 DNAJC3 Achchuthan Shanmugasundram changed review comment from: PMID:25466870 - Five individuals from two different families with demyelinating sensorimotor peripheral neuropathy and identified with homozygous DNAJC3 variants (family 1: c.580C>T (p.Arg194Ter); family 2: 72kb del (exons 6-12)).

PMID:28940199 - Cousin of family 1 from PMID:2546687 with the same variant and presented with demyelinating sensorimotor peripheral neuropathy.

PMID:32738013 - Two unrelated cases with homozygous splice site variants (case 1: c.393+2T>G; case 2: c.393+2T>C) in DNAJC3 and were reported with sensorimotor demyelinating and axonal polyneuropathy.

PMID:33486469 - Two unrelated patients identified with compound heterozygous (patient 1: p.Met1Val & p.Arg346Ter) or homozygous (p.Arg393Ter) variants, of which patient 1 had demyelinating peripheral sensorimotor neuropathy.

PMID:34654017 - One of two siblings identified with homozygous DNAJC3 variant (c.367_1370delAGAA; p.Lys456SerfsTer85) presented with demyelinating neuropathy among several other clinical manifestations.; to: PMID:25466870 - Five individuals from two different families with demyelinating sensorimotor peripheral neuropathy and identified with homozygous DNAJC3 variants (family 1: c.580C>T (p.Arg194Ter); family 2: 72kb del (exons 6-12)).

PMID:28940199 - Cousin of family 1 from PMID:2546687 with the same variant and presented with demyelinating sensorimotor peripheral neuropathy.

PMID:32738013 - Two unrelated cases with homozygous splice site variants (case 1: c.393+2T>G; case 2: c.393+2T>C) in DNAJC3 and were reported with sensorimotor demyelinating and axonal polyneuropathy.

PMID:33486469 - Two unrelated patients identified with compound heterozygous (patient 1: p.Met1Val & p.Arg346Ter) or homozygous (p.Arg393Ter) variants, of which patient 1 had demyelinating peripheral sensorimotor neuropathy.

PMID:34654017 - One of two siblings identified with homozygous DNAJC3 variant (c.367_1370delAGAA; p.Lys456SerfsTer85) presented with demyelinating neuropathy.
Hereditary neuropathy or pain disorder v3.40 DNAJC3 Achchuthan Shanmugasundram changed review comment from: PMID:25466870 - Five individuals from two different families with demyelinating sensorimotor peripheral neuropathy and identified with homozygous DNAJC3 variants (family 1: c.580C>T (p.Arg194Ter); family 2: 72kb del (exons 6-12)).

PMID:28940199 - Cousin of family 1 from PMID:2546687 with the same variant and presented with demyelinating sensorimotor peripheral neuropathy.

PMID:32738013 - Two unrelated cases with homozygous splice site variants (case 1: c.393+2T>G; case 2: c.393+2T>C) in DNAJC3 and were reported with sensorimotor demyelinating and axonal polyneuropathy among several clinical manifestations.

PMID:33486469 - Two unrelated patients identified with compound heterozygous (patient 1: p.Met1Val & p.Arg346Ter) or homozygous (p.Arg393Ter) variants, of which patient 1 had demyelinating peripheral sensorimotor neuropathy.

PMID:34654017 - One of two siblings identified with homozygous DNAJC3 variant (c.367_1370delAGAA; p.Lys456SerfsTer85) presented with demyelinating neuropathy among several other clinical manifestations.; to: PMID:25466870 - Five individuals from two different families with demyelinating sensorimotor peripheral neuropathy and identified with homozygous DNAJC3 variants (family 1: c.580C>T (p.Arg194Ter); family 2: 72kb del (exons 6-12)).

PMID:28940199 - Cousin of family 1 from PMID:2546687 with the same variant and presented with demyelinating sensorimotor peripheral neuropathy.

PMID:32738013 - Two unrelated cases with homozygous splice site variants (case 1: c.393+2T>G; case 2: c.393+2T>C) in DNAJC3 and were reported with sensorimotor demyelinating and axonal polyneuropathy.

PMID:33486469 - Two unrelated patients identified with compound heterozygous (patient 1: p.Met1Val & p.Arg346Ter) or homozygous (p.Arg393Ter) variants, of which patient 1 had demyelinating peripheral sensorimotor neuropathy.

PMID:34654017 - One of two siblings identified with homozygous DNAJC3 variant (c.367_1370delAGAA; p.Lys456SerfsTer85) presented with demyelinating neuropathy among several other clinical manifestations.
Hereditary neuropathy v1.472 DNAJC3 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient evidence (six unrelated families) available for promoting this gene to green rating.; to: Comment on list classification: There is sufficient evidence (six unrelated families) available for promoting this gene to green rating in this panel.
Hereditary neuropathy v1.472 DNAJC3 Achchuthan Shanmugasundram Classified gene: DNAJC3 as Green List (high evidence)
Hereditary neuropathy v1.472 DNAJC3 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (six unrelated families) available for promoting this gene to green rating.
Hereditary neuropathy v1.472 DNAJC3 Achchuthan Shanmugasundram Gene: dnajc3 has been classified as Green List (High Evidence).
Hereditary neuropathy v1.471 DNAJC3 Achchuthan Shanmugasundram Publications for gene: DNAJC3 were set to 25466870
Hereditary neuropathy v1.470 DNAJC3 Achchuthan Shanmugasundram reviewed gene: DNAJC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 25466870, 28940199, 32738013, 33486469, 34654017; Phenotypes: Ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus, OMIM:616192; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v3.40 DNAJC3 Achchuthan Shanmugasundram edited their review of gene: DNAJC3: Changed publications to: 25466870, 28940199, 32738013, 33486469, 34654017
Hereditary neuropathy or pain disorder v3.40 DNAJC3 Achchuthan Shanmugasundram Publications for gene: DNAJC3 were set to 25466870; 28940199; 32738013; 3348646934654017
Hereditary neuropathy or pain disorder v3.39 DNAJC3 Achchuthan Shanmugasundram Classified gene: DNAJC3 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v3.39 DNAJC3 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are six unrelated families with DNAJC3 biallelic variants and presenting with demyelinating sensorimotor peripheral neuropathy. Hence, this gene can be promoted to Green at the next GMS review.
Hereditary neuropathy or pain disorder v3.39 DNAJC3 Achchuthan Shanmugasundram Gene: dnajc3 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v3.38 DNAJC3 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: DNAJC3.
Hereditary neuropathy or pain disorder v3.38 DNAJC3 Achchuthan Shanmugasundram Publications for gene: DNAJC3 were set to 25466870
Hereditary neuropathy or pain disorder v3.37 DNAJC3 Achchuthan Shanmugasundram reviewed gene: DNAJC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 25466870, 28940199, 32738013, 3348646934654017; Phenotypes: Ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus, OMIM:616192; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v4.5 HIKESHI Hannah Knight reviewed gene: HIKESHI: Rating: GREEN; Mode of pathogenicity: None; Publications: 34111619; Phenotypes: Leukodystrophy, hypomyelinating; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v4.20 DYNC2H1 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: DYNC2H1.
Retinal disorders v4.20 DYNC2H1 Achchuthan Shanmugasundram Classified gene: DYNC2H1 as Amber List (moderate evidence)
Retinal disorders v4.20 DYNC2H1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (five unrelated cases) in support of the association of this gene with inherited retinal disease. Hence, this gene can be promoted to green rating in the next GMS review.
Retinal disorders v4.20 DYNC2H1 Achchuthan Shanmugasundram Gene: dync2h1 has been classified as Amber List (Moderate Evidence).
Retinal disorders v4.19 DYNC2H1 Achchuthan Shanmugasundram Phenotypes for gene: DYNC2H1 were changed from to retinitis pigmentosa, MONDO:0019200
Retinal disorders v4.18 DYNC2H1 Achchuthan Shanmugasundram Publications for gene: DYNC2H1 were set to
Retinal disorders v4.17 DYNC2H1 Achchuthan Shanmugasundram reviewed gene: DYNC2H1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32753734; Phenotypes: retinitis pigmentosa, MONDO:0019200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dystonia, chorea or related movement disorder, adult onset v3.6 UCHL1 Sarah Leigh Mode of inheritance for gene: UCHL1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - childhood onset v4.22 UCHL1 Sarah Leigh Tag Q3_23_MOI tag was added to gene: UCHL1.
Ataxia and cerebellar anomalies - childhood onset v4.22 UCHL1 Sarah Leigh commented on gene: UCHL1: Childhood onset cerebellar ataxia and has been reported in both Spastic paraplegia 79A, autosomal dominant, OMIM:620221 and Spastic paraplegia 79B, autosomal recessive, OMIM:615491, therefore, the mode of inheritance for this gene should be: BOTH monoallelic and biallelic, autosomal or pseudoautosomal.
Ataxia and cerebellar anomalies - childhood onset v4.22 UCHL1 Sarah Leigh edited their review of gene: UCHL1: Changed rating: GREEN
Dystonia, chorea or related movement disorder, adult onset v3.5 UCHL1 Sarah Leigh changed review comment from: In addition to previous reports of Spastic paraplegia 79, autosomal recessive (OMIM:615491), PMID: 35986737 reports a neurodegenerative disorder with spasticity, ataxia, neuropathy, and optic atrophy in cases with heterozygous UCHL1 variants. The variants included 13 heterozygous loss-of-function variants (15 families) and a heterozygous in-frame insertion (3 families). The affected individuals mainly presented with spasticity (24/31), ataxia (28/31), neuropathy (11/21), and optic atrophy (9/17), it was also noted in PMID: 35986737 that the condition onset in dominant cases was median 49 years (12-70 years) and in recessive was 7.5 years (2-10 years).; to: In addition to previous reports of Spastic paraplegia 79, autosomal recessive (OMIM:615491), PMID: 35986737 reports a neurodegenerative disorder with spasticity, ataxia, neuropathy, and optic atrophy in cases with heterozygous UCHL1 variants. The variants included 13 heterozygous loss-of-function variants (15 families) and a heterozygous in-frame insertion (3 families). The affected individuals mainly presented with spasticity (24/31), ataxia (28/31), neuropathy (11/21), and optic atrophy (9/17), it was also noted in PMID: 35986737 that the condition onset in dominant cases was median 49 years (12-70 years) and in recessive was 7.5 years (2-10 years). However, dystonia was only reported in one case in this study (Table 5S).
Hereditary ataxia, adult onset v4.17 UCHL1 Sarah Leigh Tag Q3_23_promote_green tag was added to gene: UCHL1.
Tag Q3_23_MOI tag was added to gene: UCHL1.
Hereditary spastic paraplegia, adult onset v3.13 UCHL1 Sarah Leigh Classified gene: UCHL1 as Amber List (moderate evidence)
Hereditary spastic paraplegia, adult onset v3.13 UCHL1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Hereditary spastic paraplegia, adult onset v3.13 UCHL1 Sarah Leigh Gene: uchl1 has been classified as Amber List (Moderate Evidence).
Hereditary ataxia, adult onset v4.17 UCHL1 Sarah Leigh Classified gene: UCHL1 as Amber List (moderate evidence)
Hereditary ataxia, adult onset v4.17 UCHL1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Hereditary ataxia, adult onset v4.17 UCHL1 Sarah Leigh Gene: uchl1 has been classified as Amber List (Moderate Evidence).
Hereditary ataxia, adult onset v4.16 UCHL1 Sarah Leigh edited their review of gene: UCHL1: Changed rating: GREEN
Hereditary ataxia, adult onset v4.16 UCHL1 Sarah Leigh changed review comment from: In addition to previous reports of Spastic paraplegia 79, autosomal recessive (OMIM:615491), PMID: 35986737 reports a neurodegenerative disorder with spasticity, ataxia, neuropathy, and optic atrophy in cases with heterozygous UCHL1 variants. The variants included 13 heterozygous loss-of-function variants (15 families) and a heterozygous in-frame insertion (3 families). The affected individuals mainly presented with spasticity (24/31), ataxia (28/31), neuropathy (11/21), and optic atrophy (9/17), it was also noted in PMID: 35986737 that the condition onset in dominant cases was median 49 years (12-70 years) and in recessive was 7.5 years (2-10 years).; to: In addition to previous reports of Spastic paraplegia 79, autosomal recessive (OMIM:615491), PMID: 35986737 reports a neurodegenerative disorder with spasticity, ataxia, neuropathy, and optic atrophy in cases with heterozygous UCHL1 variants. The variants included 13 heterozygous loss-of-function variants (15 families) and a heterozygous in-frame insertion (3 families). The affected individuals mainly presented with spasticity (24/31), ataxia (28/31), neuropathy (11/21), and optic atrophy (9/17), it was also noted in PMID: 35986737 that the condition onset in dominant cases was median 49 years (12-70 years) and in recessive was 7.5 years (2-10 years).
Hereditary spastic paraplegia, adult onset v3.12 UCHL1 Sarah Leigh Tag Q3_23_promote_green tag was added to gene: UCHL1.
Tag Q3_23_MOI tag was added to gene: UCHL1.
Hereditary spastic paraplegia, adult onset v3.12 UCHL1 Sarah Leigh edited their review of gene: UCHL1: Added comment: Spasticity was reported in at least six families carrying heterozygous UCHL1 variants (PMID: 35986737, figure 2 & table S5). Overall, the disease onset for Spastic paraplegia 79A, autosomal dominant, OMIM:620221 had a median of 49 years (12-70years).; Changed rating: GREEN; Changed publications to: 35986737
Hereditary spastic paraplegia, childhood onset v4.15 UCHL1 Sarah Leigh Tag Q3_23_MOI tag was added to gene: UCHL1.
Hereditary spastic paraplegia, childhood onset v4.15 UCHL1 Sarah Leigh reviewed gene: UCHL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23359680, 28007905, 35986737; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Optic neuropathy v4.5 UCHL1 Sarah Leigh Tag Q3_23_MOI tag was added to gene: UCHL1.
Optic neuropathy v4.5 UCHL1 Sarah Leigh reviewed gene: UCHL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23359680, 28007905, 35986737; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary ataxia v1.331 UCHL1 Sarah Leigh Phenotypes for gene: UCHL1 were changed from Spastic paraplegia 79, autosomal recessive, OMIM:615491 to Spastic paraplegia 79B, autosomal recessive, OMIM:615491; early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome, MONDO:0014209; Spastic paraplegia 79A, autosomal dominant, OMIM:620221
Ataxia and cerebellar anomalies - childhood onset v4.22 UCHL1 Sarah Leigh Phenotypes for gene: UCHL1 were changed from Spastic paraplegia 79, autosomal recessive, OMIM:615491; early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome, MONDO:0014209 to Spastic paraplegia 79B, autosomal recessive, OMIM:615491; early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome, MONDO:0014209; Spastic paraplegia 79A, autosomal dominant, OMIM:620221
Dystonia, chorea or related movement disorder, adult onset v3.5 UCHL1 Sarah Leigh Phenotypes for gene: UCHL1 were changed from Spastic paraplegia 79, autosomal recessive, OMIM:615491; early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome, MONDO:0014209; ?{Parkinson disease 5, susceptibility to}, OMIM:613643; Parkinson disease 5, autosomal dominant, susceptibility to' MONDO:0013340 to {?Parkinson disease 5, susceptibility to}, OMIM:613643; Parkinson disease 5, autosomal dominant, susceptibility to, MONDO:0013340; Spastic paraplegia 79B, autosomal recessive, OMIM:615491; early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome, MONDO:0014209; Spastic paraplegia 79A, autosomal dominant, OMIM:620221
Hereditary ataxia, adult onset v4.16 UCHL1 Sarah Leigh Phenotypes for gene: UCHL1 were changed from Spastic paraplegia 79, autosomal recessive, OMIM:615491; early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome, MONDO:0014209 to Spastic paraplegia 79B, autosomal recessive, OMIM:615491; early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome, MONDO:0014209; Spastic paraplegia 79A, autosomal dominant, OMIM:620221
Neurodegenerative disorders, adult onset v4.31 UCHL1 Sarah Leigh Phenotypes for gene: UCHL1 were changed from {?Parkinson disease 5, susceptibility to}, OMIM:613643; Parkinson disease 5, autosomal dominant, susceptibility to, MONDO:0013340; Spastic paraplegia 79, autosomal recessive, OMIM:615491; early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome, MONDO:0014209; Spastic paraplegia 79A, autosomal dominant, OMIM:620221 to {?Parkinson disease 5, susceptibility to}, OMIM:613643; Parkinson disease 5, autosomal dominant, susceptibility to, MONDO:0013340; Spastic paraplegia 79B, autosomal recessive, OMIM:615491; early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome, MONDO:0014209; Spastic paraplegia 79A, autosomal dominant, OMIM:620221
Hereditary spastic paraplegia, adult onset v3.12 UCHL1 Sarah Leigh Phenotypes for gene: UCHL1 were changed from Spastic paraplegia 79, autosomal recessive, OMIM:615491; early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome, MONDO:0014209; Spastic paraplegia 79A, autosomal dominant, OMIM:620221 to Spastic paraplegia 79B, autosomal recessive, OMIM:615491; early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome, MONDO:0014209; Spastic paraplegia 79A, autosomal dominant, OMIM:620221
Hereditary spastic paraplegia, childhood onset v4.15 UCHL1 Sarah Leigh Phenotypes for gene: UCHL1 were changed from Spastic paraplegia 79, autosomal recessive, OMIM:615491; early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome, MONDO:0014209; Spastic paraplegia 79A, autosomal dominant, OMIM:620221 to Spastic paraplegia 79B, autosomal recessive, OMIM:615491; early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome, MONDO:0014209; Spastic paraplegia 79A, autosomal dominant, OMIM:620221
Optic neuropathy v4.5 UCHL1 Sarah Leigh Phenotypes for gene: UCHL1 were changed from Spastic paraplegia 79, autosomal recessive, OMIM:615491; early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome, MONDO:0014209; Spastic paraplegia 79A, autosomal dominant, OMIM:620221 to Spastic paraplegia 79B, autosomal recessive, OMIM:615491; early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome, MONDO:0014209; Spastic paraplegia 79A, autosomal dominant, OMIM:620221
Neurodegenerative disorders, adult onset v4.30 UCHL1 Sarah Leigh Phenotypes for gene: UCHL1 were changed from ?{Parkinson disease 5, susceptibility to}; Early onset ataxia and optic neuropathy to {?Parkinson disease 5, susceptibility to}, OMIM:613643; Parkinson disease 5, autosomal dominant, susceptibility to, MONDO:0013340; Spastic paraplegia 79, autosomal recessive, OMIM:615491; early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome, MONDO:0014209; Spastic paraplegia 79A, autosomal dominant, OMIM:620221
Hereditary spastic paraplegia, adult onset v3.11 UCHL1 Sarah Leigh Phenotypes for gene: UCHL1 were changed from Spastic paraplegia 79, autosomal recessive, OMIM:615491; early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome, MONDO:0014209 to Spastic paraplegia 79, autosomal recessive, OMIM:615491; early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome, MONDO:0014209; Spastic paraplegia 79A, autosomal dominant, OMIM:620221
Hereditary spastic paraplegia, childhood onset v4.14 UCHL1 Sarah Leigh Phenotypes for gene: UCHL1 were changed from Spastic paraplegia 79, autosomal recessive, OMIM:615491 to Spastic paraplegia 79, autosomal recessive, OMIM:615491; early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome, MONDO:0014209; Spastic paraplegia 79A, autosomal dominant, OMIM:620221
Hereditary spastic paraplegia, childhood onset v4.13 AMFR Achchuthan Shanmugasundram changed review comment from: PMID:37119330 - 20 individuals from 8 unrelated consanguineous families of various origins were identified with autosomal recessive variants in AMFR gene. All patients had early disease onset (<3 years), including motor delay, lower limb hyperreflexia and spastic paraplegia that match the typical phenotypes of hereditary spastic paraplegia.
Sources: Literature; to: PMID:37119330 - 20 individuals from 8 unrelated consanguineous families of various origins were identified with autosomal recessive variants in AMFR gene. All patients had early disease onset (<3 years), including motor delay, lower limb hyperreflexia and spastic paraplegia that match the typical phenotypes of hereditary spastic paraplegia.

This gene has been associated with relevant phenotypes in OMIM (MIM #620379), but not in Gene2Phenotype.
Sources: Literature
Optic neuropathy v4.4 UCHL1 Sarah Leigh Phenotypes for gene: UCHL1 were changed from Spastic paraplegia 79, autosomal recessive, 615491 to Spastic paraplegia 79, autosomal recessive, OMIM:615491; early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome, MONDO:0014209; Spastic paraplegia 79A, autosomal dominant, OMIM:620221
Hereditary spastic paraplegia, childhood onset v4.13 AMFR Achchuthan Shanmugasundram Classified gene: AMFR as Amber List (moderate evidence)
Hereditary spastic paraplegia, childhood onset v4.13 AMFR Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to green rating at the next GMS review.
Hereditary spastic paraplegia, childhood onset v4.13 AMFR Achchuthan Shanmugasundram Gene: amfr has been classified as Amber List (Moderate Evidence).
Hereditary spastic paraplegia, childhood onset v4.12 AMFR Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: AMFR.
Hereditary spastic paraplegia, childhood onset v4.12 AMFR Achchuthan Shanmugasundram gene: AMFR was added
gene: AMFR was added to Childhood onset hereditary spastic paraplegia. Sources: Literature
Mode of inheritance for gene: AMFR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AMFR were set to 37119330
Phenotypes for gene: AMFR were set to Spastic paraplegia 89, autosomal recessive, OMIM:620379
Review for gene: AMFR was set to GREEN
Added comment: PMID:37119330 - 20 individuals from 8 unrelated consanguineous families of various origins were identified with autosomal recessive variants in AMFR gene. All patients had early disease onset (<3 years), including motor delay, lower limb hyperreflexia and spastic paraplegia that match the typical phenotypes of hereditary spastic paraplegia.
Sources: Literature
Neurodegenerative disorders, adult onset v4.29 UCHL1 Sarah Leigh Publications for gene: UCHL1 were set to PMID: 23359680
Hereditary spastic paraplegia, childhood onset v4.11 UCHL1 Sarah Leigh Publications for gene: UCHL1 were set to 23359680; 28007905; 29735986; 32656641; 11555633; 33159930
Optic neuropathy v4.3 UCHL1 Sarah Leigh Publications for gene: UCHL1 were set to 29735986; 23359680; 28007905
Early onset or syndromic epilepsy v4.70 CNOT9 Achchuthan Shanmugasundram Classified gene: CNOT9 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.70 CNOT9 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (five unrelated cases) for this gene to be promoted to Green at the next major update.
Early onset or syndromic epilepsy v4.70 CNOT9 Achchuthan Shanmugasundram Gene: cnot9 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.69 CNOT9 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: CNOT9.
Early onset or syndromic epilepsy v4.69 CNOT9 Achchuthan Shanmugasundram Phenotypes for gene: CNOT9 were changed from epilepsy, MONDO:0005027 to epilepsy, MONDO:0005027
Early onset or syndromic epilepsy v4.69 CNOT9 Achchuthan Shanmugasundram Phenotypes for gene: CNOT9 were changed from epilepsy, MONDO:0005027 to epilepsy, MONDO:0005027
Early onset or syndromic epilepsy v4.69 CNOT9 Achchuthan Shanmugasundram Phenotypes for gene: CNOT9 were changed from intellectual disability, MONDO:0001071 to epilepsy, MONDO:0005027
Early onset or syndromic epilepsy v4.68 CNOT9 Achchuthan Shanmugasundram edited their review of gene: CNOT9: Changed phenotypes to: epilepsy, MONDO:0005027
Intellectual disability v5.217 CNOT9 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: CNOT9.
Intellectual disability v5.217 CNOT9 Achchuthan Shanmugasundram Classified gene: CNOT9 as Amber List (moderate evidence)
Intellectual disability v5.217 CNOT9 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (seven unrelated cases) for this gene to be promoted to Green at the next major update.
Intellectual disability v5.217 CNOT9 Achchuthan Shanmugasundram Gene: cnot9 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.68 CNOT9 Achchuthan Shanmugasundram gene: CNOT9 was added
gene: CNOT9 was added to Early onset or syndromic epilepsy. Sources: Literature
Mode of inheritance for gene: CNOT9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CNOT9 were set to 37092538
Phenotypes for gene: CNOT9 were set to intellectual disability, MONDO:0001071
Review for gene: CNOT9 was set to GREEN
Added comment: PMID:37092538 - Seven unrelated individuals with de novo variants in CNOT9 gene (one individual each with variants p.Arg46Gly, p.Pro131Leu and p.Arg227His and four individuals with p.Arg292Trp) were reported with a neurodevelopmental disorder. All affected persons have intellectual disability (three severe, three mild and one unclassified) and five of them have seizures.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability v5.216 CNOT9 Achchuthan Shanmugasundram gene: CNOT9 was added
gene: CNOT9 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: CNOT9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CNOT9 were set to 37092538
Phenotypes for gene: CNOT9 were set to intellectual disability, MONDO:0001071
Review for gene: CNOT9 was set to GREEN
Added comment: PMID:37092538 - Seven unrelated individuals with de novo variants in CNOT9 gene (one individual each with variants p.Arg46Gly, p.Pro131Leu and p.Arg227His and four individuals with p.Arg292Trp) were reported with a neurodevelopmental disorder. All affected persons have intellectual disability (three severe, three mild and one unclassified) and five of them have seizures.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Dystonia, chorea or related movement disorder, childhood onset v3.23 SLC30A9 Achchuthan Shanmugasundram Classified gene: SLC30A9 as Amber List (moderate evidence)
Dystonia, chorea or related movement disorder, childhood onset v3.23 SLC30A9 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are six unrelated families with childhood onset dystonia or choreoathetosis reported with biallelic variants in this gene. Hence, this gene can be promoted to Green at the next major update.
Dystonia, chorea or related movement disorder, childhood onset v3.23 SLC30A9 Achchuthan Shanmugasundram Gene: slc30a9 has been classified as Amber List (Moderate Evidence).
Dystonia, chorea or related movement disorder, childhood onset v3.22 SLC30A9 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: SLC30A9.
Dystonia, chorea or related movement disorder, childhood onset v3.22 SLC30A9 Achchuthan Shanmugasundram gene: SLC30A9 was added
gene: SLC30A9 was added to Childhood onset dystonia, chorea or related movement disorder. Sources: Literature
Mode of inheritance for gene: SLC30A9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC30A9 were set to 28334855; 34716203; 37041080
Phenotypes for gene: SLC30A9 were set to Birk-Landau-Perez syndrome, OMIM:617595
Review for gene: SLC30A9 was set to GREEN
Added comment: PMID:28334855 - Six patients from a large multigenerational Bedouin kindred had onset of different combinations of intellectual disability, muscle weakness, oculomotor apraxia, and nephropathy in early childhood and they were identified with a homozygous variant in SLC30A9 gene (c.1047_1049delGCA; p.A350del). The age of onset of movement disorder was around 1-2 years of age.

PMID:34716203 - A girl of African-American descent was identified with compound heterozygous variants in SLC30A9 gene (c.40delA & c.86_87dupCC) and was reported with a cerebrorenal syndrome. She presented around one year of age with microcephaly and global developmental delay. She also had bilateral sensorineural hearing loss and later developed dystonic movements affecting the whole body (onset was around 5-10 years of age).

PMID:37041080 - Eight individuals from four unrelated families were reported with SLC30A9-related disease and they presented with intellectual disability and progressive hyperkinetic movement disorder, associated with oculomotor apraxia and ptosis despite phenotypic variability. The two families of British Pakistani descent harboured homozygous c.1253G>T (p.Gly418Val) variant, Egyptian Palestinian family harboured homozygous c.1049delCAG (pAla350del) variant, while family of European Australian descent had compound heterozygous variants (c.1083dup/ p.Val362Cysfs*5, and c.1413A>G/ p.Ser471=). The age of onset of movement disorder in these patients ranged from around 1-2 years to 16 years of age.

This gene has been associated with relevant phenotypes in OMIM (MIM #617595), but not yet in Gene2Phenotype.
Sources: Literature
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Classified gene: SLC30A9 as Amber List (moderate evidence)
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are six unrelated families with Intellectual disability/ global developmental delay reported with biallelic variants in this gene. Hence, this gene can be promoted to Green at the next major update.
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Gene: slc30a9 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Classified gene: SLC30A9 as Amber List (moderate evidence)
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are six unrelated families with Intellectual disability/ global developmental delay reported with biallelic variants in this gene. Hence, this gene can be promoted to Green at the next major update.
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Gene: slc30a9 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There are six unrelated families with Intellectual disability/ global developmental delay reported with biallelic variants in this gene. Hence, this gene can be promoted to Green at the next major update.; to: Comment on list classification: There are six unrelated families with Intellectual disability/ global developmental delay reported with biallelic variants in this gene. Hence, this gene can be promoted to Green at the next major update.
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There are six unrelated families with Intellectual disability/ global developmental delay reported with biallelic variants in this gene. Hence, this gene can be promoted to Green at the next major update.; to: Comment on list classification: There are six unrelated families with Intellectual disability/ global developmental delay reported with biallelic variants in this gene. Hence, this gene can be promoted to Green at the next major update.
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Classified gene: SLC30A9 as Amber List (moderate evidence)
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are six unrelated families with Intellectual disability/ global developmental delay reported with biallelic variants in this gene. Hence, this gene can be promoted to Green at the next major update.
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Gene: slc30a9 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Classified gene: SLC30A9 as Amber List (moderate evidence)
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are six unrelated families with Intellectual disability/ global developmental delay reported with biallelic variants in this gene. Hence, this gene can be promoted to Green at the next major update.
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Gene: slc30a9 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.214 SLC30A9 Achchuthan Shanmugasundram Phenotypes for gene: SLC30A9 were changed from Birk-Landau-Perez syndrome, OMIM:617595 to Birk-Landau-Perez syndrome, OMIM:617595
Intellectual disability v5.214 SLC30A9 Achchuthan Shanmugasundram Phenotypes for gene: SLC30A9 were changed from Birk-Landau-Perez syndrome, OMIM:617595 to Birk-Landau-Perez syndrome, OMIM:617595
Intellectual disability v5.213 SLC30A9 Achchuthan Shanmugasundram Phenotypes for gene: SLC30A9 were changed from Birk-Landau-Perez syndrome, OMIM:617595 to Birk-Landau-Perez syndrome, OMIM:617595
Intellectual disability v5.213 SLC30A9 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: SLC30A9.
Intellectual disability v5.213 SLC30A9 Achchuthan Shanmugasundram Phenotypes for gene: SLC30A9 were changed from Birk-Landau-Perez syndrome, OMIM:617595 to Birk-Landau-Perez syndrome, OMIM:617595
Intellectual disability v5.213 SLC30A9 Achchuthan Shanmugasundram Phenotypes for gene: SLC30A9 were changed from ?Birk-Landau-Perez syndrome 617595 to Birk-Landau-Perez syndrome, OMIM:617595
Intellectual disability v5.212 SLC30A9 Achchuthan Shanmugasundram Publications for gene: SLC30A9 were set to 28334855
Intellectual disability v5.211 SLC30A9 Achchuthan Shanmugasundram reviewed gene: SLC30A9: Rating: GREEN; Mode of pathogenicity: None; Publications: 28334855, 34716203, 37041080; Phenotypes: Birk-Landau-Perez syndrome, OMIM:617595; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v4.17 MCOLN1 Achchuthan Shanmugasundram changed review comment from: Mucolipidosis type IV caused by biallelic variants in MCOLN1 gene ism a lysosomal disease that primarily affects the central nervous system. It manifests with severely impaired psychomotor development, and later onset, gradual neurological decline paralleled by cerebellar degeneration and neuroaxonal injury. In addition, they also manifest tetinal dystrophy, which develops in the first years of life and rapidly progresses in adolescence, leaving patients legally blind by the second decade (PMID:33965501).

The following are some of the reported cases:
PMID:17239335 - Compound heterozygous variants in MCOLN1 were identified in a patient with mucolipidosis type IV (ML IV), who had low visual acuity and cloudy corneas since 2 years of age, progressive decrease in visual acuity since the age of 9 years.
PMID:25156245 - An Italian child with ML IV was identified with homozygous MCOLN1 variants (c.395_397delCTG & c.468_474dupTTGGACC), while his parents were heterozygous for the same variants. Ophthalmological manifestations included esotropia, bilateral corneal clouding and severe myopia.
PMID:35205297 - Six patients from two Omani families with ML IV were identified with a novel variant (c.237+5G>A) in MCOLN1 gene, which is not present in control subjects screened with a high-resolution melting (HRM) assay. The patients displayed ophthalmic manifestations including corneal haziness, pigmentary retinopathy and ERG-rod cone dysfunction.

This gene has also been associated with relevant phenotypes both in OMIM (MIM #252650) and DD and eye panels of Gene2Phenotype (with 'definitive' rating). The ophthalmological manifestations including corneal clouding, progressive retinal degeneration and optic atrophy has been reported as part of the OMIM phenotype.; to: Mucolipidosis type IV caused by biallelic variants in MCOLN1 gene ism a lysosomal disease that primarily affects the central nervous system. It manifests with severely impaired psychomotor development, and later onset, gradual neurological decline paralleled by cerebellar degeneration and neuroaxonal injury. In addition, they also manifest retinal dystrophy, which develops in the first years of life and rapidly progresses in adolescence, leaving patients legally blind by the second decade (PMID:33965501).

The following are some of the reported cases:
PMID:17239335 - Compound heterozygous variants in MCOLN1 were identified in a patient with mucolipidosis type IV (ML IV), who had low visual acuity and cloudy corneas since 2 years of age, progressive decrease in visual acuity since the age of 9 years.
PMID:25156245 - An Italian child with ML IV was identified with homozygous MCOLN1 variants (c.395_397delCTG & c.468_474dupTTGGACC), while his parents were heterozygous for the same variants. Ophthalmological manifestations included esotropia, bilateral corneal clouding and severe myopia.
PMID:35205297 - Six patients from two Omani families with ML IV were identified with a novel variant (c.237+5G>A) in MCOLN1 gene, which is not present in control subjects screened with a high-resolution melting (HRM) assay. The patients displayed ophthalmic manifestations including corneal haziness, pigmentary retinopathy and ERG-rod cone dysfunction.

This gene has also been associated with relevant phenotypes both in OMIM (MIM #252650) and DD and eye panels of Gene2Phenotype (with 'definitive' rating). The ophthalmological manifestations including corneal clouding, progressive retinal degeneration and optic atrophy has been reported as part of the OMIM phenotype.
Retinal disorders v4.17 MCOLN1 Achchuthan Shanmugasundram Classified gene: MCOLN1 as Amber List (moderate evidence)
Retinal disorders v4.17 MCOLN1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Siying Lin, there is sufficient evidence for this gene to be added with a green rating in this panel as patients with MCOLN1-associated mucolipidosis IV present with a limited ocular phenotype including retinal dystrophy.
Retinal disorders v4.17 MCOLN1 Achchuthan Shanmugasundram Gene: mcoln1 has been classified as Amber List (Moderate Evidence).
Retinal disorders v4.16 MCOLN1 Achchuthan Shanmugasundram Publications for gene: MCOLN1 were set to 17239335; 1488220; 18326692
Retinal disorders v4.15 MCOLN1 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: MCOLN1.
Retinal disorders v4.15 MCOLN1 Achchuthan Shanmugasundram reviewed gene: MCOLN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 17239335, 25156245, 33965501, 35205297; Phenotypes: Mucolipidosis IV, OMIM:252650; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v4.15 PYGM Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There are four unrelated cases in support of the association of this gene to retinal disorders. Hence, this gene can be rated green in the next major update.; to: Comment on list classification: As reviewed by Siying Lin, there are four unrelated cases in support of the association of this gene to retinal disorders. Hence, this gene can be rated green in the next major update.
Retinal disorders v4.15 PYGM Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: PYGM.
Tag Q3_23_NHS_review tag was added to gene: PYGM.
Retinal disorders v4.15 PYGM Achchuthan Shanmugasundram Classified gene: PYGM as Amber List (moderate evidence)
Retinal disorders v4.15 PYGM Achchuthan Shanmugasundram Added comment: Comment on list classification: There are four unrelated cases in support of the association of this gene to retinal disorders. Hence, this gene can be rated green in the next major update.
Retinal disorders v4.15 PYGM Achchuthan Shanmugasundram Gene: pygm has been classified as Amber List (Moderate Evidence).
Retinal disorders v4.14 PYGM Achchuthan Shanmugasundram Phenotypes for gene: PYGM were changed from Macular dystrophy, retinopathy to macular dystrophy, retinal, MONDO:0031166
Retinal disorders v4.13 PYGM Achchuthan Shanmugasundram Publications for gene: PYGM were set to PMID 30316539
Retinal disorders v4.12 PYGM Achchuthan Shanmugasundram reviewed gene: PYGM: Rating: GREEN; Mode of pathogenicity: None; Publications: 30316539; Phenotypes: macular dystrophy, retinal, MONDO:0031166; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dystonia, chorea or related movement disorder, childhood onset v3.21 TMEM151A Achchuthan Shanmugasundram Tag Q3_23_NHS_review tag was added to gene: TMEM151A.
Dystonia, chorea or related movement disorder, childhood onset v3.21 TMEM151A Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient evidence (more than 40 unrelated cases and supporting functional evidence) available in support of the association of this gene to PKD. Hence, this gene can be rated Green in the next major update.; to: Comment on list classification: There is sufficient evidence (more than 40 unrelated cases and supporting functional evidence) available in support of the association of this gene to PKD with onset in childhood/ adolescence. Hence, this gene can be rated Green in the next major update.
Dystonia, chorea or related movement disorder, childhood onset v3.21 TMEM151A Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: TMEM151A.
Dystonia, chorea or related movement disorder, childhood onset v3.21 TMEM151A Achchuthan Shanmugasundram Classified gene: TMEM151A as Amber List (moderate evidence)
Dystonia, chorea or related movement disorder, childhood onset v3.21 TMEM151A Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (more than 40 unrelated cases and supporting functional evidence) available in support of the association of this gene to PKD. Hence, this gene can be rated Green in the next major update.
Dystonia, chorea or related movement disorder, childhood onset v3.21 TMEM151A Achchuthan Shanmugasundram Gene: tmem151a has been classified as Amber List (Moderate Evidence).
Dystonia, chorea or related movement disorder, childhood onset v3.20 TMEM151A Achchuthan Shanmugasundram Phenotypes for gene: TMEM151A were changed from Episodic kinesigenic dyskinesia 3 to Episodic kinesigenic dyskinesia 3, OMIM:620245
Dystonia, chorea or related movement disorder, childhood onset v3.19 TMEM151A Achchuthan Shanmugasundram Publications for gene: TMEM151A were set to 34518509; 34820915; 35587630; 35707035; 35727387
Dystonia, chorea or related movement disorder, childhood onset v3.18 TMEM151A Achchuthan Shanmugasundram changed review comment from: PMID:34518509 - Nine individuals from three unrelated Chines families with paroxysmal kinesigenic dyskinesia (PKD) were identified with autosomal dominant variants in TMEM151A gene. In addition, 8 unrelated patients (isolated cases) with sporadic occurrence of PKD were also identified with heterozygous variants, of which three patients inherited variants from an unaffected parent, suggesting incomplete penetrance. The age of onset of symptoms ranged between 9 and 15 years. In addition, supporting mouse model and in vitro functional assays suggested loss of function as the mechanism of disease.

PMID:34820915 - 29 PRRT2-negative Chinese patients from 25 families with PKD identified with 24 heterozygous variants in TMEM151A gene. The mean age of onset of symptoms was 12.93 years, with 13 patients reported with spontaneous remission of the disease around 21 years of age.

PMID:35587630 - De novo missense variant in TMEM151A was identified in a French man with PKD and he presented with brief attacks of dystonia after 16 years of age.

PMID:35707035 - Screening of patients with PRRT2-negative PKD and other movement disorders identified two novel variants in TMEM151A gene in two patients with PKD.

PMID:35727387 - Heterozygous missense variant was identified in four affected members of a 3-generation Chinese family with PKD and the variant segregated with the disorder in the family.


This gene has been associated with relevant phenotype in OMIM (MIM #620245), but not in Gene2Phenotype.; to: PMID:34518509 - Nine individuals from three unrelated Chines families with paroxysmal kinesigenic dyskinesia (PKD) were identified with autosomal dominant variants in TMEM151A gene. In addition, 8 unrelated patients (isolated cases) with sporadic occurrence of PKD were also identified with heterozygous variants, of which three patients inherited variants from an unaffected parent, suggesting incomplete penetrance. The age of onset of symptoms ranged between 9 and 15 years. In addition, supporting mouse model and in vitro functional assays suggested loss of function as the mechanism of disease.

PMID:34820915 - 29 PRRT2-negative Chinese patients from 25 families with PKD identified with 24 heterozygous variants in TMEM151A gene. The mean age of onset of symptoms was 12.93 years, with 13 patients reported with spontaneous remission of the disease around 21 years of age.

PMID:35587630 - De novo missense variant in TMEM151A was identified in a French man with PKD and he presented with brief attacks of dystonia after 16 years of age.

PMID:35707035 - Screening of patients with PRRT2-negative PKD and other movement disorders identified two novel variants in TMEM151A gene in two patients with PKD.

PMID:35727387 - Heterozygous missense variant was identified in four affected members of a 3-generation Chinese family with PKD and the variant segregated with the disorder in the family.

PMID:36724570 - Three patients presenting with PKD were identified with different TMEM151A variants.

This gene has been associated with relevant phenotype in OMIM (MIM #620245), but not in Gene2Phenotype.
Dystonia, chorea or related movement disorder, childhood onset v3.18 TMEM151A Achchuthan Shanmugasundram edited their review of gene: TMEM151A: Changed publications to: 34518509, 34820915, 35587630, 35707035, 35727387, 36724570
Dystonia, chorea or related movement disorder, childhood onset v3.18 TMEM151A Achchuthan Shanmugasundram Publications for gene: TMEM151A were set to (PMID: 34518509; 35707035; 36724570; 34820915)
Dystonia, chorea or related movement disorder, childhood onset v3.17 TMEM151A Achchuthan Shanmugasundram reviewed gene: TMEM151A: Rating: GREEN; Mode of pathogenicity: None; Publications: 34518509, 34820915, 35587630, 35707035, 35727387; Phenotypes: Episodic kinesigenic dyskinesia 3, OMIM:620245; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Possible mitochondrial disorder, nuclear genes v3.33 PPOX Achchuthan Shanmugasundram changed review comment from: As reviewed by Zornitza Stark and suggested in PMID:25778941, Variegate porphyria (VP) should be included in this panel.

Autosomal dominat variegate porphyria (VP):

VP is usually caused by autosomal dominant variants in PPOX gene in the majority of the cases.

PMID:30476629 - Eight unrelated individuals with seven different variants in heterozygous state were reported with VP.

Autosomal dominant variants in this gene have also been associated with VP in OMIM (MIM #176200).

Autosomal recessive variegate porphyria (VP):

PMID:9540991 - A severely affected female proband with recessive VP was identified with two missense compound heterozygous variants in PPOX gene (p.Gly169Glu & p.Gly358Arg), as detected by heteroduplex analysis, automated sequencing, and allele specific oligonucleotide hybridization.

PMID:10870850 - Two unrelated South African cases with variegate porphyria were reported with onset of the disease usually in infancy and with severe skin manifestations. The variant detection included combined SSCP-heteroduplex analysis followed by direct sequencing and both had the common p.Arg59Trp variant, while the other variant was p.Tyr348Cys in one and p.Arg138Pro in the other.

PMID:32247286 - A case of VP was reported from a family with only cutaneous manifestations and was identified with two heterozygous missense variants in PPOX gene (p.Gly41Cys and p.Trp42Arg). The same variants were identified in patient's mother who had skin lesions, whereas father had no clinical involvement and did not have any of these variants. The familly study showed that the two variants occur in cis on the same allele.

PMID:33159949 - A novel homozygous variant in PPOX gene (c.808G>T) was identified in a patient with autosomal recessive form of VP.

Overall, the autosomal recessive form of VP usually occurs early in in fancy and have markedly reduced levels of protoporphyrinogen oxidase than autosomal dominant form. Autosomal recessive VP has not yet been reported in OMIM.; to: As reviewed by Zornitza Stark in 'Mitochondrial disorders' panel and suggested in PMID:25778941, Variegate porphyria (VP) should be included in this panel.

Autosomal dominat variegate porphyria (VP):

VP is usually caused by autosomal dominant variants in PPOX gene in the majority of the cases.

PMID:30476629 - Eight unrelated individuals with seven different variants in heterozygous state were reported with VP.

Autosomal dominant variants in this gene have also been associated with VP in OMIM (MIM #176200).

Autosomal recessive variegate porphyria (VP):

PMID:9540991 - A severely affected female proband with recessive VP was identified with two missense compound heterozygous variants in PPOX gene (p.Gly169Glu & p.Gly358Arg), as detected by heteroduplex analysis, automated sequencing, and allele specific oligonucleotide hybridization.

PMID:10870850 - Two unrelated South African cases with variegate porphyria were reported with onset of the disease usually in infancy and with severe skin manifestations. The variant detection included combined SSCP-heteroduplex analysis followed by direct sequencing and both had the common p.Arg59Trp variant, while the other variant was p.Tyr348Cys in one and p.Arg138Pro in the other.

PMID:32247286 - A case of VP was reported from a family with only cutaneous manifestations and was identified with two heterozygous missense variants in PPOX gene (p.Gly41Cys and p.Trp42Arg). The same variants were identified in patient's mother who had skin lesions, whereas father had no clinical involvement and did not have any of these variants. The familly study showed that the two variants occur in cis on the same allele.

PMID:33159949 - A novel homozygous variant in PPOX gene (c.808G>T) was identified in a patient with autosomal recessive form of VP.

Overall, the autosomal recessive form of VP usually occurs early in in fancy and have markedly reduced levels of protoporphyrinogen oxidase than autosomal dominant form. Autosomal recessive VP has not yet been reported in OMIM.
Possible mitochondrial disorder, nuclear genes v3.33 PPOX Achchuthan Shanmugasundram Classified gene: PPOX as Amber List (moderate evidence)
Possible mitochondrial disorder, nuclear genes v3.33 PPOX Achchuthan Shanmugasundram Added comment: Comment on list classification: There are more than three unrelated cases each with both monoallelic and biallelic variants in PPOX gene. Hence, this gene should be promoted to Green at the next GMS update and the MOI should be updated from 'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown' to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal'.
Possible mitochondrial disorder, nuclear genes v3.33 PPOX Achchuthan Shanmugasundram Gene: ppox has been classified as Amber List (Moderate Evidence).
Possible mitochondrial disorder, nuclear genes v3.32 PPOX Achchuthan Shanmugasundram Publications for gene: PPOX were set to
Possible mitochondrial disorder, nuclear genes v3.31 PPOX Achchuthan Shanmugasundram Mode of inheritance for gene: PPOX was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Possible mitochondrial disorder, nuclear genes v3.30 PPOX Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: PPOX.
Possible mitochondrial disorder, nuclear genes v3.30 PPOX Achchuthan Shanmugasundram reviewed gene: PPOX: Rating: GREEN; Mode of pathogenicity: None; Publications: 9540991, 10870850, 25778941, 30476629, 32247286, 33159949; Phenotypes: Porphyria variegata, OMIM:176200; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v3.37 PPOX Achchuthan Shanmugasundram Publications for gene: PPOX were set to
Hereditary neuropathy or pain disorder v3.36 PPOX Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: Comment on mode of inheritance: There are at least three cases of variegate porphyria reported with biallelic variants in PPOX gene and sensory neuropathy. Hence, the MOI should be updated from "MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted" to "BOTH monoallelic and biallelic, autosomal or pseudoautosomal" in the next GMS review.
Hereditary neuropathy or pain disorder v3.36 PPOX Achchuthan Shanmugasundram Mode of inheritance for gene: PPOX was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v3.35 PPOX Achchuthan Shanmugasundram Tag Q3_23_MOI tag was added to gene: PPOX.
Hereditary neuropathy or pain disorder v3.35 PPOX Achchuthan Shanmugasundram reviewed gene: PPOX: Rating: GREEN; Mode of pathogenicity: None; Publications: 8290408, 10870850, 11286631; Phenotypes: Porphyria variegata, OMIM:176200, Sensory neuropathy, HP:0000763; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary neuropathy v1.470 PPOX Achchuthan Shanmugasundram Mode of inheritance for gene: PPOX was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary neuropathy v1.469 PPOX Achchuthan Shanmugasundram Tag Q3_23_MOI was removed from gene: PPOX.
Hereditary neuropathy v1.469 PPOX Achchuthan Shanmugasundram changed review comment from: Comment on mode of inheritance: There are at least three cases of variegate porphyria reported with biallelic variants in PPOX gene and sensory neuropathy. Hence, the MOI can be updated from "MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted" to "BOTH monoallelic and biallelic, autosomal or pseudoautosomal" in the next GMS review.; to: Comment on mode of inheritance: There are at least three cases of variegate porphyria reported with biallelic variants in PPOX gene and sensory neuropathy. Hence, the MOI should be updated from "MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted" to "BOTH monoallelic and biallelic, autosomal or pseudoautosomal".
Hereditary neuropathy v1.469 PPOX Achchuthan Shanmugasundram Tag Q3_23_MOI tag was added to gene: PPOX.
Hereditary neuropathy v1.469 PPOX Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There are at least three cases of variegate porphyria reported with biallelic variants in PPOX gene and sensory neuropathy. Hence, the MOI can be updated from "MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted" to "BOTH monoallelic and biallelic, autosomal or pseudoautosomal" in the next GMS review.
Hereditary neuropathy v1.469 PPOX Achchuthan Shanmugasundram Mode of inheritance for gene: PPOX was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy v1.468 PPOX Achchuthan Shanmugasundram Publications for gene: PPOX were set to 8290408; 10870850; 11286631
Hereditary neuropathy v1.467 PPOX Achchuthan Shanmugasundram Publications for gene: PPOX were set to
Hereditary neuropathy v1.466 PPOX Achchuthan Shanmugasundram edited their review of gene: PPOX: Changed rating: GREEN
Hereditary neuropathy v1.466 PPOX Achchuthan Shanmugasundram reviewed gene: PPOX: Rating: ; Mode of pathogenicity: None; Publications: 8290408, 10870850, 11286631; Phenotypes: Porphyria variegata, OMIM:176200, Sensory neuropathy, HP:0000763; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mitochondrial disorders v4.62 PPOX Achchuthan Shanmugasundram Publications for gene: PPOX were set to 9540991; 9811936; 10870850; 12859407; 25778941; 30476629; 32247286; 33159949
Mitochondrial disorders v4.62 PPOX Achchuthan Shanmugasundram Publications for gene: PPOX were set to
Mitochondrial disorders v4.61 PPOX Achchuthan Shanmugasundram Mode of inheritance for gene: PPOX was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mitochondrial disorders v4.60 PPOX Achchuthan Shanmugasundram Deleted their comment
Mitochondrial disorders v4.60 PPOX Achchuthan Shanmugasundram Classified gene: PPOX as Amber List (moderate evidence)
Mitochondrial disorders v4.60 PPOX Achchuthan Shanmugasundram Added comment: Comment on list classification: There are more than three unrelated cases each with both monoallelic and biallelic variants in PPOX gene. Hence, this gene should be promoted to Green at the next GMS update and the MOI should be updated from 'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown' to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal'.
Mitochondrial disorders v4.60 PPOX Achchuthan Shanmugasundram Gene: ppox has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v4.60 PPOX Achchuthan Shanmugasundram Classified gene: PPOX as Amber List (moderate evidence)
Mitochondrial disorders v4.60 PPOX Achchuthan Shanmugasundram Added comment: Comment on list classification: There are more than three unrelated cases each with both monoallelic and biallelic variants in PPOX gene. Hence, this gene should be promoted to Green at the next GMS update and the MOI should be updated from 'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown' to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal'.
Mitochondrial disorders v4.60 PPOX Achchuthan Shanmugasundram Gene: ppox has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v4.59 PPOX Achchuthan Shanmugasundram Tag Q3_23_MOI was removed from gene: PPOX.
Tag Q3_23_promote_green tag was added to gene: PPOX.
Mitochondrial disorders v4.59 PPOX Achchuthan Shanmugasundram Tag Q3_23_MOI tag was added to gene: PPOX.
Mitochondrial disorders v4.59 PPOX Achchuthan Shanmugasundram edited their review of gene: PPOX: Changed publications to: 9540991, 10870850, 25778941, 30476629, 32247286, 33159949
Mitochondrial disorders v4.59 PPOX Achchuthan Shanmugasundram changed review comment from: Autosomal dominat variegate porphyria (VP):

VP is usually caused by autosomal dominant variants in PPOX gene in the majority of the cases.

PMID:30476629 - Eight unrelated individuals with seven different variants in heterozygous state were reported with VP.

Autosomal dominant variants in this gene have also been associated with VP in OMIM (MIM #176200).

Autosomal recessive variegate porphyria (VP):

PMID:9540991 - A severely affected female proband with recessive VP was identified with two missense compound heterozygous variants in PPOX gene (p.Gly169Glu & p.Gly358Arg), as detected by heteroduplex analysis, automated sequencing, and allele specific oligonucleotide hybridization.

PMID:10870850 - Two unrelated South African cases with variegate porphyria were reported with onset of the disease usually in infancy and with severe skin manifestations. The variant detection included combined SSCP-heteroduplex analysis followed by direct sequencing and both had the common p.Arg59Trp variant, while the other variant was p.Tyr348Cys in one and p.Arg138Pro in the other.

PMID:32247286 - A case of VP was reported from a family with only cutaneous manifestations and was identified with two heterozygous missense variants in PPOX gene (p.Gly41Cys and p.Trp42Arg). The same variants were identified in patient's mother who had skin lesions, whereas father had no clinical involvement and did not have any of these variants. The familly study showed that the two variants occur in cis on the same allele.

PMID:33159949 - A novel homozygous variant in PPOX gene (c.808G>T) was identified in a patient with autosomal recessive form of VP.

Overall, the autosomal recessive form of VP usually occurs early in in fancy and have markedly reduced levels of protoporphyrinogen oxidase than autosomal dominant form. Autosomal recessive VP has not yet been reported in OMIM.
; to: As reviewed by Zornitza Stark and suggested in PMID:25778941, Variegate porphyria (VP) should be included in this panel.

Autosomal dominat variegate porphyria (VP):

VP is usually caused by autosomal dominant variants in PPOX gene in the majority of the cases.

PMID:30476629 - Eight unrelated individuals with seven different variants in heterozygous state were reported with VP.

Autosomal dominant variants in this gene have also been associated with VP in OMIM (MIM #176200).

Autosomal recessive variegate porphyria (VP):

PMID:9540991 - A severely affected female proband with recessive VP was identified with two missense compound heterozygous variants in PPOX gene (p.Gly169Glu & p.Gly358Arg), as detected by heteroduplex analysis, automated sequencing, and allele specific oligonucleotide hybridization.

PMID:10870850 - Two unrelated South African cases with variegate porphyria were reported with onset of the disease usually in infancy and with severe skin manifestations. The variant detection included combined SSCP-heteroduplex analysis followed by direct sequencing and both had the common p.Arg59Trp variant, while the other variant was p.Tyr348Cys in one and p.Arg138Pro in the other.

PMID:32247286 - A case of VP was reported from a family with only cutaneous manifestations and was identified with two heterozygous missense variants in PPOX gene (p.Gly41Cys and p.Trp42Arg). The same variants were identified in patient's mother who had skin lesions, whereas father had no clinical involvement and did not have any of these variants. The familly study showed that the two variants occur in cis on the same allele.

PMID:33159949 - A novel homozygous variant in PPOX gene (c.808G>T) was identified in a patient with autosomal recessive form of VP.

Overall, the autosomal recessive form of VP usually occurs early in in fancy and have markedly reduced levels of protoporphyrinogen oxidase than autosomal dominant form. Autosomal recessive VP has not yet been reported in OMIM.
Mitochondrial disorders v4.59 PPOX Achchuthan Shanmugasundram changed review comment from: PMID:30476629 - Eight unrelated individuals with seven different variants in heterozygous state were reported with Variegate porphyria (VP).

PMID:32247286 - A case of VP was reported from a family with only cutaneous manifestations and was identified with two heterozygous missense variants in PPOX gene (p.Gly41Cys and p.Trp42Arg). The same variants were identified in patient's mother who had skin lesions, whereas father had no clinical involvement and did not have any of these variants. The familly study showed that the two variants occur in cis on the same allele.

Autosomal dominant variants in this gene have been associated with Variegate porphyria in OMIM (MIM #176200).; to: Autosomal dominat variegate porphyria (VP):

VP is usually caused by autosomal dominant variants in PPOX gene in the majority of the cases.

PMID:30476629 - Eight unrelated individuals with seven different variants in heterozygous state were reported with VP.

Autosomal dominant variants in this gene have also been associated with VP in OMIM (MIM #176200).

Autosomal recessive variegate porphyria (VP):

PMID:9540991 - A severely affected female proband with recessive VP was identified with two missense compound heterozygous variants in PPOX gene (p.Gly169Glu & p.Gly358Arg), as detected by heteroduplex analysis, automated sequencing, and allele specific oligonucleotide hybridization.

PMID:10870850 - Two unrelated South African cases with variegate porphyria were reported with onset of the disease usually in infancy and with severe skin manifestations. The variant detection included combined SSCP-heteroduplex analysis followed by direct sequencing and both had the common p.Arg59Trp variant, while the other variant was p.Tyr348Cys in one and p.Arg138Pro in the other.

PMID:32247286 - A case of VP was reported from a family with only cutaneous manifestations and was identified with two heterozygous missense variants in PPOX gene (p.Gly41Cys and p.Trp42Arg). The same variants were identified in patient's mother who had skin lesions, whereas father had no clinical involvement and did not have any of these variants. The familly study showed that the two variants occur in cis on the same allele.

PMID:33159949 - A novel homozygous variant in PPOX gene (c.808G>T) was identified in a patient with autosomal recessive form of VP.

Overall, the autosomal recessive form of VP usually occurs early in in fancy and have markedly reduced levels of protoporphyrinogen oxidase than autosomal dominant form. Autosomal recessive VP has not yet been reported in OMIM.
Mitochondrial disorders v4.59 PPOX Achchuthan Shanmugasundram edited their review of gene: PPOX: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mitochondrial disorders v4.59 PPOX Achchuthan Shanmugasundram reviewed gene: PPOX: Rating: GREEN; Mode of pathogenicity: None; Publications: 30476629, 32247286; Phenotypes: Porphyria variegata, OMIM:176200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Monogenic hearing loss v4.10 PTPRQ Achchuthan Shanmugasundram changed review comment from: PMID:29309402 - A heterozygous nonsense variant (c.6881G>A; p.Trp2294Ter) was identified in a four-generation German family with nonsyndromic mild to severe hearing loss of the mid- to high frequencies and onset from early childhood to second decade in seven members.

PMID:31655630 - The same variant (c.6881G>A; p.Trp2294Ter) was identified in a five-generation Polish family with autosomal dominant non-syndromic hearing loss (ADNSHL). Using genome-wide linkage analysis, the authors also found that the studied Polish family and the original German family derive from a common ancestor.

PMID:33229591 - PTPRQ variants p.Gly383Glu and p.Arg841Trp were identified in multiplex family age-related hearing loss (mARHL) cases, while p.Ser1022Arg, c.4286-1G>T and p.Leu879Argfs*20 were identified with simplex/sporadic age-related hearing loss (sARHL) cases. However, p.Ser321Cys was identified in control cases with normal hearing.; to: PMID:29309402 - A heterozygous nonsense variant (c.6881G>A; p.Trp2294Ter) was identified in a four-generation German family with nonsyndromic mild to severe hearing loss of the mid- to high frequencies and onset from early childhood to second decade in seven members.

PMID:31655630 - The same variant (c.6881G>A; p.Trp2294Ter) was identified in a five-generation Polish family with autosomal dominant non-syndromic hearing loss (ADNSHL). Using genome-wide linkage analysis, the authors also found that the studied Polish family and the original German family derive from a common ancestor.

PMID:33229591 - PTPRQ variants p.Gly383Glu and p.Arg841Trp were identified in multiplex family age-related hearing loss (mARHL) cases, while p.Ser1022Arg, c.4286-1G>T and p.Leu879Argfs*20 were identified with simplex/sporadic age-related hearing loss (sARHL) cases. However, p.Ser321Cys was identified in control cases with normal hearing.

This gene has been associated with hearing loss caused by both autosomal dominant (MIM #617663) and autosomal recessive (MIM #613391) inheritance in OMIM.
Monogenic hearing loss v4.10 PTPRQ Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: As there are sufficient cases/ variants reported with monoallelic inheritance and hearing loss, the MOI should be changed from "BIALLELIC, autosomal or pseudoautosomal" to "BOTH monoallelic and biallelic, autosomal or pseudoautosomal" in the next major review.
Monogenic hearing loss v4.10 PTPRQ Achchuthan Shanmugasundram Mode of inheritance for gene: PTPRQ was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v4.9 PTPRQ Achchuthan Shanmugasundram Tag Q3_23_MOI tag was added to gene: PTPRQ.
Monogenic hearing loss v4.9 PTPRQ Achchuthan Shanmugasundram reviewed gene: PTPRQ: Rating: GREEN; Mode of pathogenicity: None; Publications: 29309402, 31655630, 33229591; Phenotypes: Deafness, autosomal dominant 73, OMIM:617663, Deafness, autosomal recessive 84A, OMIM:613391; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal ciliopathies v3.9 PMM2 Eleanor Williams Tag Q3_23_expert_review tag was added to gene: PMM2.
Skeletal ciliopathies v3.9 PMM2 Eleanor Williams Tag Q3_23_demote_red tag was added to gene: PMM2.
Skeletal ciliopathies v3.9 PMM2 Eleanor Williams commented on gene: PMM2: After reviewing the literature no patients were found with a skeletal phenotype so demotion to red on this panel is recommended. This has been confirmed with a Genomics England clinician. It is represented on the other ciliopathy panels, so shouldn't be missed for relevant phenotypes. It was initially added as a ciliopathy mimic.
Skeletal dysplasia v4.10 EN1 Eleanor Williams changed review comment from: The Genomics England clinical team confirm that the rating of this gene should currently be amber based on 1 case and a mouse model.; to: The Genomics England clinical team confirm that the rating of this gene should currently be amber based on 1 case and a mouse model. It has been additionally added to the 'Fetal anomalies' and 'Ataxia and cerebellar anomalies - narrow panel' panels based on the phenotype.

If more cases with intellectual disability/seizures are reported then it could be additionally added to those panels at that time.
Ataxia and cerebellar anomalies - childhood onset v4.21 EN1 Eleanor Williams Tag watchlist tag was added to gene: EN1.
Ataxia and cerebellar anomalies - childhood onset v4.21 EN1 Eleanor Williams commented on gene: EN1: This gene was copied from the Skeletal dysplasia panel to the Ataxia and cerebellar anomalies - narrow panel panel. The Genomics England clinical team have agreed that Fetal anomalies is an appropriate panel for this gene and the rating should currently be amber.
Skeletal dysplasia v4.10 EN1 Eleanor Williams Tag watchlist tag was added to gene: EN1.
Fetal anomalies v3.92 EN1 Eleanor Williams Tag watchlist tag was added to gene: EN1.
Fetal anomalies v3.92 EN1 Eleanor Williams commented on gene: EN1: This gene was copied from the Skeletal dysplasia panel to the Fetal anomalies panel. The Genomics England clinical team have agreed that Fetal anomalies is an appropriate panel for this gene and the rating should currently be amber.
Fetal anomalies v3.92 EN1 Eleanor Williams Entity copied from Skeletal dysplasia v4.10
Fetal anomalies v3.92 EN1 Eleanor Williams gene: EN1 was added
gene: EN1 was added to Fetal anomalies. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: EN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EN1 were set to 33568816
Phenotypes for gene: EN1 were set to ENDOVE syndrome, limb-only type, MIM# 619217; ENDOVE syndrome, limb-brain type, MIM# 619218
Ataxia and cerebellar anomalies - childhood onset v4.21 EN1 Eleanor Williams Entity copied from Skeletal dysplasia v4.10
Ataxia and cerebellar anomalies - childhood onset v4.21 EN1 Eleanor Williams gene: EN1 was added
gene: EN1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: EN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EN1 were set to 33568816
Phenotypes for gene: EN1 were set to ENDOVE syndrome, limb-only type, MIM# 619217; ENDOVE syndrome, limb-brain type, MIM# 619218
Skeletal dysplasia v4.10 EN1 Eleanor Williams commented on gene: EN1: The Genomics England clinical team confirm that the rating of this gene should currently be amber based on 1 case and a mouse model.
Mosaic skin disorders - Deep sequencing v2.9 FGFR2 Arina Puzriakova Phenotypes for gene: FGFR2 were changed from Epdermal naevi to Keratinocytic epidermal naevi (KENs); Naevoid acanthosis nigricans; RAVEN (round and velvety epidermal naevus)
Vascular skin disorders v1.51 EPHB4 Arina Puzriakova Phenotypes for gene: EPHB4 were changed from CAPILLARY MALFORMATION-ARTERIOVENOUS MALFORMATION 2, OMIM:618196 to Capillary malformation-arteriovenous malformation 2, OMIM:618196
Hereditary haemorrhagic telangiectasia v3.2 EPHB4 Arina Puzriakova Phenotypes for gene: EPHB4 were changed from Capillary malformation-arteriovenous malformation 2, 618196; Capillary malformation, epistaxis, telangiectasia, cerebral AVM to Capillary malformation-arteriovenous malformation 2, OMIM:618196; Capillary malformation, epistaxis, telangiectasia, cerebral AVM
Primary lymphoedema v3.3 EPHB4 Arina Puzriakova Phenotypes for gene: EPHB4 were changed from Lymphatic malformation 7 617300 to Lymphatic malformation 7, OMIM:617300
Fetal anomalies v3.91 EPHB4 Arina Puzriakova Phenotypes for gene: EPHB4 were changed from hydrops fetalis gene to Lymphatic malformation 7, OMIM:617300; hydrops fetalis
Fetal hydrops v1.61 EPHB4 Arina Puzriakova Mode of inheritance for gene: EPHB4 was changed from MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed) to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal hydrops v1.60 EPHB4 Arina Puzriakova Phenotypes for gene: EPHB4 were changed from Lymphatic malformation 7, MIM#617300 to Lymphatic malformation 7, OMIM:617300
Fetal hydrops v1.59 EPHB4 Arina Puzriakova Classified gene: EPHB4 as Green List (high evidence)
Fetal hydrops v1.59 EPHB4 Arina Puzriakova Added comment: Comment on list classification: Sufficient evidence to support hydrops fetalis association as part of MIM:617300, with 3 variants listed in OMIM from 3 families, each with multiple affected individuals (PMIDs: 27400125 and 29905864). Already Green on Fetal anomalies GMS panel.
Fetal hydrops v1.59 EPHB4 Arina Puzriakova Gene: ephb4 has been classified as Green List (High Evidence).
Mosaic skin disorders - Deep sequencing v2.8 EPHB4 Arina Puzriakova Tag watchlist tag was added to gene: EPHB4.
Mosaic skin disorders - Deep sequencing v2.8 EPHB4 Arina Puzriakova Classified gene: EPHB4 as Amber List (moderate evidence)
Mosaic skin disorders - Deep sequencing v2.8 EPHB4 Arina Puzriakova Added comment: Comment on list classification: Rating Amber for now as only a single case with mosaicism has been reported to date. The patients phenotype was comparable to germline cases but another independent report or functional studies of the variant would help corroborate this association before classifying as diagnostic-grade.
Mosaic skin disorders - Deep sequencing v2.8 EPHB4 Arina Puzriakova Gene: ephb4 has been classified as Amber List (Moderate Evidence).
Mosaic skin disorders - Deep sequencing v2.7 EPHB4 Arina Puzriakova Publications for gene: EPHB4 were set to PMID: 30760892
Mosaic skin disorders - Deep sequencing v2.6 EPHB4 Arina Puzriakova Phenotypes for gene: EPHB4 were changed from Capillary malformation-arteriovenous malformation 2 (MIM 618196); Lymphatic malformation 7 (MIM 617300) to Capillary malformation-arteriovenous malformation 2, OMIM:618196
Mosaic skin disorders - Deep sequencing v2.5 EPHB4 Arina Puzriakova commented on gene: EPHB4
Beckwith-Wiedemann syndrome v0.2 CDKN1C Achchuthan Shanmugasundram Mode of inheritance for gene: CDKN1C was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Beckwith-Wiedemann syndrome v0.1 CDKN1C Achchuthan Shanmugasundram edited their review of gene: CDKN1C: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Infantile nystagmus v1.10 DAGLA Achchuthan Shanmugasundram Classified gene: DAGLA as Green List (high evidence)
Infantile nystagmus v1.10 DAGLA Achchuthan Shanmugasundram Added comment: Comment on list classification: There are more than three unrelated cases with infantile nystagmus and hence this gene can be promoted to green in this panel.
Infantile nystagmus v1.10 DAGLA Achchuthan Shanmugasundram Gene: dagla has been classified as Green List (High Evidence).
Infantile nystagmus v1.9 DAGLA Achchuthan Shanmugasundram Phenotypes for gene: DAGLA were changed from developmental delay; ataxia; complex oculomotor abnormality (nystagmus) to congenital nystagmus, MONDO:0005712
Infantile nystagmus v1.8 DAGLA Achchuthan Shanmugasundram Publications for gene: DAGLA were set to PMID: 35737950
Infantile nystagmus v1.7 DAGLA Achchuthan Shanmugasundram Mode of pathogenicity for gene: DAGLA was changed from Other to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Infantile nystagmus v1.6 DAGLA Achchuthan Shanmugasundram reviewed gene: DAGLA: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 35737950; Phenotypes: congenital nystagmus, MONDO:0005712; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia v1.330 DAGLA Achchuthan Shanmugasundram changed review comment from: As reviewed by Irina Ziravecka, there are nine children from eight unrelated families reported with heterozygous de novo variants in DAGLA gene and presenting with a neuro-ocular phenotype characterized by developmental delay, ataxia and complex oculomotor abnormality. All nine children had ataxia and the age of these children ranged between 4 and 15 years of age. In addition, the functional data suggests potential mechanisms include DAGLA haploinsufficiency at the plasma membrane or dominant negative effect (PMID:35737950).

This gene has not yet been associated with any relevant phenotypes either in OMIM or in Gene2Phenotype.; to: As reviewed by Irina Ziravecka, there are nine children from eight unrelated families reported with heterozygous de novo variants in DAGLA gene and presenting with a neuro-ocular phenotype characterized by developmental delay, ataxia and complex oculomotor abnormality. All nine children had ataxia and the age of these children ranged between 4 and 15 years of age. In addition, the functional data suggests potential mechanisms include DAGLA haploinsufficiency at the plasma membrane or dominant negative effect (PMID:35737950).

This gene has not yet been associated with any relevant phenotypes either in OMIM or in Gene2Phenotype.
Epidermolysis bullosa and congenital skin fragility v2.4 ATP2A2 Arina Puzriakova Phenotypes for gene: ATP2A2 were changed from Darier disease, OMIM:124200 to Darier-White disease, OMIM:124200
Mitochondrial disorders v4.59 ANO10 Sarah Leigh Phenotypes for gene: ANO10 were changed from Spinocerebellar ataxia, autosomal recessive 10, 613728 to Spinocerebellar ataxia, autosomal recessive 10, OMIM:613728; autosomal recessive spinocerebellar ataxia 10, MONDO:0013392
Mitochondrial disorders v4.58 ANO10 Sarah Leigh Publications for gene: ANO10 were set to
Mitochondrial disorders v4.57 ANO10 Sarah Leigh Tag Q3_23_expert_review tag was added to gene: ANO10.
Mitochondrial disorders v4.57 BTD Sarah Leigh Tag Q3_23_expert_review tag was added to gene: BTD.
Mucopolysaccharidosis type IH or S v0.2 Achchuthan Shanmugasundram Panel name changed from Mucopolysaccharidosis type IH/S to Mucopolysaccharidosis type IH or S
Mucolipidosis II and III Alpha or Beta v0.2 Achchuthan Shanmugasundram Panel name changed from Mucolipidosis II and III Alpha/Beta to Mucolipidosis II and III Alpha or Beta
Mitochondrial disorders v4.57 ANO10 Sarah Leigh reviewed gene: ANO10: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mitochondrial disorders v4.57 BTD Sarah Leigh reviewed gene: BTD: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Hereditary ataxia v1.330 DAGLA Achchuthan Shanmugasundram Classified gene: DAGLA as Green List (high evidence)
Hereditary ataxia v1.330 DAGLA Achchuthan Shanmugasundram Added comment: Comment on list classification: There are eight unrelated cases associating monoallelic variants in DAGLA with ataxia. Hence, this gene can be rated Green.
Hereditary ataxia v1.330 DAGLA Achchuthan Shanmugasundram Gene: dagla has been classified as Green List (High Evidence).
Hereditary ataxia v1.329 DAGLA Achchuthan Shanmugasundram Phenotypes for gene: DAGLA were changed from developmental delay; ataxia; complex oculomotor abnormality to Ataxia, HP:0001251
Hereditary ataxia v1.328 DAGLA Achchuthan Shanmugasundram Mode of pathogenicity for gene: DAGLA was changed from Other to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Hereditary ataxia v1.327 DAGLA Achchuthan Shanmugasundram Publications for gene: DAGLA were set to PMID: 35737950
Hereditary ataxia v1.326 DAGLA Achchuthan Shanmugasundram reviewed gene: DAGLA: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 35737950; Phenotypes: Ataxia, HP:0001251; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mitochondrial disorders v4.57 BTD Sarah Leigh Phenotypes for gene: BTD were changed from Biotinidase deficiency to Biotinidase deficiency, OMIM:253260; biotinidase deficiency, MONDO:0009665
Ataxia and cerebellar anomalies - childhood onset v4.20 DAGLA Achchuthan Shanmugasundram Classified gene: DAGLA as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - childhood onset v4.20 DAGLA Achchuthan Shanmugasundram Added comment: Comment on list classification: There are eight unrelated cases associating monoallelic variants in DAGLA with ataxia. Hence, this gene should be promoted to Green rating at the next major review.
Ataxia and cerebellar anomalies - childhood onset v4.20 DAGLA Achchuthan Shanmugasundram Gene: dagla has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.211 DAGLA Achchuthan Shanmugasundram Mode of pathogenicity for gene: DAGLA was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability v5.211 DAGLA Achchuthan Shanmugasundram Mode of pathogenicity for gene: DAGLA was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability v5.211 DAGLA Achchuthan Shanmugasundram Mode of pathogenicity for gene: DAGLA was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Ataxia and cerebellar anomalies - childhood onset v4.19 DAGLA Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: DAGLA.
Intellectual disability v5.211 DAGLA Achchuthan Shanmugasundram Mode of pathogenicity for gene: DAGLA was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability v5.211 DAGLA Achchuthan Shanmugasundram Mode of pathogenicity for gene: DAGLA was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability v5.210 DAGLA Achchuthan Shanmugasundram Mode of pathogenicity for gene: DAGLA was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Ataxia and cerebellar anomalies - childhood onset v4.19 DAGLA Achchuthan Shanmugasundram Mode of pathogenicity for gene: DAGLA was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability v5.210 DAGLA Achchuthan Shanmugasundram Mode of pathogenicity for gene: DAGLA was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability v5.210 DAGLA Achchuthan Shanmugasundram Mode of pathogenicity for gene: DAGLA was changed from Other to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability v5.209 DAGLA Achchuthan Shanmugasundram edited their review of gene: DAGLA: Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Ataxia and cerebellar anomalies - childhood onset v4.18 DAGLA Achchuthan Shanmugasundram edited their review of gene: DAGLA: Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Ataxia and cerebellar anomalies - childhood onset v4.18 DAGLA Achchuthan Shanmugasundram gene: DAGLA was added
gene: DAGLA was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: DAGLA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DAGLA were set to 35737950
Phenotypes for gene: DAGLA were set to Ataxia, HP:0001251
Review for gene: DAGLA was set to GREEN
Added comment: There are nine children from eight unrelated families reported with heterozygous de novo variants in DAGLA gene and presenting with a neuro-ocular phenotype characterized by developmental delay, ataxia and complex oculomotor abnormality. All nine children had ataxia and the age of these children ranged between 4 and 15 years of age. In addition, the functional data suggests potential mechanisms include DAGLA haploinsufficiency at the plasma membrane or dominant negative effect (PMID:35737950).

This gene has not yet been associated with any relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability v5.209 DAGLA Achchuthan Shanmugasundram changed review comment from: As reviewed by Irina Ziravecka, there are nine children from eight unrelated families reported with heterozygous de novo variants in DAGLA gene and presenting with a neuro-ocular phenotype characterized by developmental delay, ataxia and complex oculomotor abnormality. Of these nine children, five had intellectual disability and one had low average IQ. In addition, the functional data suggests potential mechanisms include DAGLA haploinsufficiency at the plasma membrane or dominant negative effect (PMID:35737950).; to: As reviewed by Irina Ziravecka, there are nine children from eight unrelated families reported with heterozygous de novo variants in DAGLA gene and presenting with a neuro-ocular phenotype characterized by developmental delay, ataxia and complex oculomotor abnormality. Of these nine children, five had intellectual disability and one had low average IQ. In addition, the functional data suggests potential mechanisms include DAGLA haploinsufficiency at the plasma membrane or dominant negative effect (PMID:35737950).

This gene has not yet been associated with any relevant phenotypes either in OMIM or in Gene2Phenotype.
Mosaic skin disorders - Deep sequencing v2.5 ATP2A2 Arina Puzriakova Tag Q3_23_promote_green tag was added to gene: ATP2A2.
Tag Q3_23_NHS_review tag was added to gene: ATP2A2.
Mosaic skin disorders - Deep sequencing v2.5 ATP2A2 Arina Puzriakova Classified gene: ATP2A2 as Amber List (moderate evidence)
Mosaic skin disorders - Deep sequencing v2.5 ATP2A2 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update. At least 6 unrelated cases of mosaic Darier disease reported in literature. ATP2A2 is associated with a relevant phenotype in OMIM that also mentions somatic mosaic disease.
Mosaic skin disorders - Deep sequencing v2.5 ATP2A2 Arina Puzriakova Gene: atp2a2 has been classified as Amber List (Moderate Evidence).
Mosaic skin disorders - Deep sequencing v2.4 ATP2A2 Arina Puzriakova Phenotypes for gene: ATP2A2 were changed from to Segmental Darier disease OMIM:124200; Darier-White disease OMIM:124200; Acrokeratosis verruciformis, OMIM:101900
Mosaic skin disorders - Deep sequencing v2.3 ATP2A2 Arina Puzriakova Publications for gene: ATP2A2 were set to
Segmental overgrowth disorders - Deep sequencing v3.6 ARAF Arina Puzriakova Tag treatable was removed from gene: ARAF.
Tag Q3_23_NHS_review tag was added to gene: ARAF.
Mosaic skin disorders - Deep sequencing v2.2 ARAF Arina Puzriakova Tag treatable tag was added to gene: ARAF.
Segmental overgrowth disorders - Deep sequencing v3.6 ARAF Arina Puzriakova Tag treatable tag was added to gene: ARAF.
Segmental overgrowth disorders - Deep sequencing v3.6 ARAF Arina Puzriakova changed review comment from: Comment on list classification: New gene added by Tom Cullup (GOSH). ARAF is not currently associated with any phenotype in OMIM or G2P. Although only two patients have been reported with the same missense variant, functional studies including an animal model provide strong support of pathogenicity (outlined below). Evidence of this variant specific gene-disease relationship is sufficiently compelling but the phenotype is more within scope of the R110 Segmental overgrowth disorders – Deep sequencing panel. Therefore rating as amber on this panel and green on R110.

- PMID: 31263281 (2019):
To date, only two unrelated patients have been reported with the same missense GoF variant in ARAF (c.640T>C:p.S214P) who both had a complex lymphatic anomaly (no haplotype analysis was done). Cells transduced with ARAF-S214P showed elevated ERK1/2 activity, enhanced lymphangiogenic capacity, and disassembly of actin skeleton and VE-cadherin junctions. A zebrafish model recapitulated the lymphatic phenotype. The cellular, zebrafish and patient clinical phenotypes were all rescued with with a MEK inhibitor.; to: Comment on list classification: New gene added by Tom Cullup (GOSH). ARAF is not currently associated with any phenotype in OMIM or G2P. Although only two patients have been reported with the same missense variant, functional studies including an animal model provide strong support of pathogenicity (outlined below). Evidence of this variant specific gene-disease relationship is sufficiently compelling to rate this gene as green at the next GMS panel update.

- PMID: 31263281 (2019):
To date, only two unrelated patients have been reported with the same missense GoF variant in ARAF (c.640T>C:p.S214P) who both had a complex lymphatic anomaly (no haplotype analysis was done). Cells transduced with ARAF-S214P showed elevated ERK1/2 activity, enhanced lymphangiogenic capacity, and disassembly of actin skeleton and VE-cadherin junctions. A zebrafish model recapitulated the lymphatic phenotype. The cellular, zebrafish and patient clinical phenotypes were all rescued with with a MEK inhibitor.
Segmental overgrowth disorders - Deep sequencing v3.6 ARAF Arina Puzriakova Tag Q3_23_promote_green tag was added to gene: ARAF.
Segmental overgrowth disorders - Deep sequencing v3.6 ARAF Arina Puzriakova Entity copied from Mosaic skin disorders - deep sequencing v2.2
Segmental overgrowth disorders - Deep sequencing v3.6 ARAF Arina Puzriakova gene: ARAF was added
gene: ARAF was added to Segmental overgrowth disorders - Deep sequencing. Sources: Expert Review Amber,Expert list
Mode of inheritance for gene: ARAF was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: ARAF were set to 31263281
Phenotypes for gene: ARAF were set to central conducting lymphatic anomaly
Penetrance for gene: ARAF were set to unknown
Mode of pathogenicity for gene: ARAF was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Mosaic skin disorders - Deep sequencing v2.2 ARAF Arina Puzriakova Classified gene: ARAF as Amber List (moderate evidence)
Mosaic skin disorders - Deep sequencing v2.2 ARAF Arina Puzriakova Added comment: Comment on list classification: New gene added by Tom Cullup (GOSH). ARAF is not currently associated with any phenotype in OMIM or G2P. Although only two patients have been reported with the same missense variant, functional studies including an animal model provide strong support of pathogenicity (outlined below). Evidence of this variant specific gene-disease relationship is sufficiently compelling but the phenotype is more within scope of the R110 Segmental overgrowth disorders – Deep sequencing panel. Therefore rating as amber on this panel and green on R110.

- PMID: 31263281 (2019):
To date, only two unrelated patients have been reported with the same missense GoF variant in ARAF (c.640T>C:p.S214P) who both had a complex lymphatic anomaly (no haplotype analysis was done). Cells transduced with ARAF-S214P showed elevated ERK1/2 activity, enhanced lymphangiogenic capacity, and disassembly of actin skeleton and VE-cadherin junctions. A zebrafish model recapitulated the lymphatic phenotype. The cellular, zebrafish and patient clinical phenotypes were all rescued with with a MEK inhibitor.
Mosaic skin disorders - Deep sequencing v2.2 ARAF Arina Puzriakova Gene: araf has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.209 DAGLA Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: DAGLA.
Intellectual disability v5.209 DAGLA Achchuthan Shanmugasundram Phenotypes for gene: DAGLA were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.209 DAGLA Achchuthan Shanmugasundram Phenotypes for gene: DAGLA were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.209 DAGLA Achchuthan Shanmugasundram Phenotypes for gene: DAGLA were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.209 DAGLA Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.209 DAGLA Achchuthan Shanmugasundram Phenotypes for gene: DAGLA were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.209 DAGLA Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.209 DAGLA Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.209 DAGLA Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.209 DAGLA Achchuthan Shanmugasundram Phenotypes for gene: DAGLA were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.209 DAGLA Achchuthan Shanmugasundram Phenotypes for gene: DAGLA were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.209 DAGLA Achchuthan Shanmugasundram Phenotypes for gene: DAGLA were changed from developmental delay; ataxia; complex oculomotor abnormality to intellectual disability, MONDO:0001071
Intellectual disability v5.208 DAGLA Achchuthan Shanmugasundram Classified gene: DAGLA as Amber List (moderate evidence)
Intellectual disability v5.208 DAGLA Achchuthan Shanmugasundram Added comment: Comment on list classification: There are more than 3 unrelated cases associating monoallelic variants in this gene to intellectual disability. Hence, this gene can be promoted to Green rating at the next GMS update.
Intellectual disability v5.208 DAGLA Achchuthan Shanmugasundram Gene: dagla has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.208 DAGLA Achchuthan Shanmugasundram Classified gene: DAGLA as Amber List (moderate evidence)
Intellectual disability v5.208 DAGLA Achchuthan Shanmugasundram Added comment: Comment on list classification: There are more than 3 unrelated cases associating monoallelic variants in this gene to intellectual disability. Hence, this gene can be promoted to Green rating at the next GMS update.
Intellectual disability v5.208 DAGLA Achchuthan Shanmugasundram Gene: dagla has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.208 DAGLA Achchuthan Shanmugasundram Classified gene: DAGLA as Amber List (moderate evidence)
Intellectual disability v5.208 DAGLA Achchuthan Shanmugasundram Added comment: Comment on list classification: There are more than 3 unrelated cases associating monoallelic variants in this gene to intellectual disability. Hence, this gene can be promoted to Green rating at the next GMS update.
Intellectual disability v5.208 DAGLA Achchuthan Shanmugasundram Gene: dagla has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.208 DAGLA Achchuthan Shanmugasundram Classified gene: DAGLA as Amber List (moderate evidence)
Intellectual disability v5.208 DAGLA Achchuthan Shanmugasundram Added comment: Comment on list classification: There are more than 3 unrelated cases associating monoallelic variants in this gene to intellectual disability. Hence, this gene can be promoted to Green rating at the next GMS update.
Intellectual disability v5.208 DAGLA Achchuthan Shanmugasundram Gene: dagla has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.207 DAGLA Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.207 DAGLA Achchuthan Shanmugasundram Classified gene: DAGLA as Amber List (moderate evidence)
Intellectual disability v5.207 DAGLA Achchuthan Shanmugasundram Added comment: Comment on list classification: There are more than 3 unrelated cases associating monoallelic variants in this gene to intellectual disability. Hence, this gene can be promoted to Green rating at the next GMS update.
Intellectual disability v5.207 DAGLA Achchuthan Shanmugasundram Gene: dagla has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.207 DAGLA Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.207 DAGLA Achchuthan Shanmugasundram Classified gene: DAGLA as Amber List (moderate evidence)
Intellectual disability v5.207 DAGLA Achchuthan Shanmugasundram Added comment: Comment on list classification: There are more than 3 unrelated cases associating monoallelic variants in this gene to intellectual disability. Hence, this gene can be promoted to Green rating at the next GMS update.
Intellectual disability v5.207 DAGLA Achchuthan Shanmugasundram Gene: dagla has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.207 DAGLA Achchuthan Shanmugasundram Classified gene: DAGLA as Amber List (moderate evidence)
Intellectual disability v5.207 DAGLA Achchuthan Shanmugasundram Added comment: Comment on list classification: There are more than 3 unrelated cases associating monoallelic variants in this gene to intellectual disability. Hence, this gene can be promoted to Green rating at the next GMS update.
Intellectual disability v5.207 DAGLA Achchuthan Shanmugasundram Gene: dagla has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.206 DAGLA Achchuthan Shanmugasundram Publications for gene: DAGLA were set to 35737950
Intellectual disability v5.206 DAGLA Achchuthan Shanmugasundram Publications for gene: DAGLA were set to PMID: 35737950
Intellectual disability v5.205 DAGLA Achchuthan Shanmugasundram changed review comment from: As reviewed by Irina Ziravecka, there are nine children from eight unrelated families reported with heterozygous de novo variants in DAGLA gene and presenting with a neuro-ocular phenotype characterized by developmental delay, ataxia and complex oculomotor abnormality. Of these nine children, five had intellectual disability and one had low average IQ (PMID:35737950).; to: As reviewed by Irina Ziravecka, there are nine children from eight unrelated families reported with heterozygous de novo variants in DAGLA gene and presenting with a neuro-ocular phenotype characterized by developmental delay, ataxia and complex oculomotor abnormality. Of these nine children, five had intellectual disability and one had low average IQ. In addition, the functional data suggests potential mechanisms include DAGLA haploinsufficiency at the plasma membrane or dominant negative effect (PMID:35737950).
Intellectual disability v5.205 DAGLA Achchuthan Shanmugasundram changed review comment from: As reviewed by Irina Ziravecka, there are nine children from eight unrelated families reported with heterozygous variants in DAGLA gene and presenting with a neuro-ocular phenotype characterized by developmental delay, ataxia and complex oculomotor abnormality. Of these nine children, five had intellectual disability and one had low average IQ (PMID:35737950).; to: As reviewed by Irina Ziravecka, there are nine children from eight unrelated families reported with heterozygous de novo variants in DAGLA gene and presenting with a neuro-ocular phenotype characterized by developmental delay, ataxia and complex oculomotor abnormality. Of these nine children, five had intellectual disability and one had low average IQ (PMID:35737950).
Intellectual disability v5.205 DAGLA Achchuthan Shanmugasundram reviewed gene: DAGLA: Rating: GREEN; Mode of pathogenicity: None; Publications: 35737950; Phenotypes: intellectual disability, MONDO:0001071; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Retinal disorders v4.12 PYGM Siying Lin gene: PYGM was added
gene: PYGM was added to Retinal disorders. Sources: Literature
Mode of inheritance for gene: PYGM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PYGM were set to PMID 30316539
Phenotypes for gene: PYGM were set to Macular dystrophy, retinopathy
Mode of pathogenicity for gene: PYGM was set to Other
Review for gene: PYGM was set to GREEN
Added comment: Mahroo et al (PMID 30316539) report on 4 individuals with McArdle disease and biallelic variants in PYGM and similar retinopathy affecting the macula. Screening results for mutations in a number of macular dystrophy genes were negative, supporting the association of this retinopathy with McArdle disease
Sources: Literature
Hereditary ataxia, adult onset v4.15 TDP1 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: TDP1.
Hereditary ataxia, adult onset v4.15 TDP1 Achchuthan Shanmugasundram edited their review of gene: TDP1: Changed rating: GREEN
Hereditary ataxia, adult onset v4.15 TDP1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: This gene can now be promoted to AMBER as there are three unrelated cases. The "founder-effect" tag has been added as they are all of Middle Eastern descent and harboured the same homozygous variant. However, the additional patient reported by Ian Berry (Leeds Genetics Laboratory) had the same variant in compound heterozygous state with another novel variant. Hence, this gene can be considered for promotion to GREEN rating at the next major review.; to: Comment on list classification: This gene can now be promoted to AMBER as there are three unrelated cases. The "founder-effect" tag has been added as they are all of Middle Eastern descent and harboured the same homozygous variant. However, the additional patient reported by Ian Berry (Leeds Genetics Laboratory) had the same variant in compound heterozygous state with another novel variant. As there is an additional variant reported, this gene can be considered for promotion to GREEN rating at the next major review.
Hereditary ataxia, adult onset v4.15 TDP1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: This gene can now be promoted to AMBER as there are three unrelated cases. The "founder-effect" tag has been added as they are all of Middle Eastern descent and harboured the same homozygous variant. Hence, it cannot be promoted to green rating.; to: Comment on list classification: This gene can now be promoted to AMBER as there are three unrelated cases. The "founder-effect" tag has been added as they are all of Middle Eastern descent and harboured the same homozygous variant. However, the additional patient reported by Ian Berry (Leeds Genetics Laboratory) had the same variant in compound heterozygous state with another novel variant. Hence, this gene can be considered for promotion to GREEN rating at the next major review.
Paroxysmal central nervous system disorders v3.1 RHOBTB2 Dmitrijs Rots reviewed gene: RHOBTB2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Clefting v4.80 AMOTL1 Arina Puzriakova Tag Q3_23_promote_green tag was added to gene: AMOTL1.
Clefting v4.80 AMOTL1 Arina Puzriakova Publications for gene: AMOTL1 were set to 33026150; 30375152
Clefting v4.79 AMOTL1 Arina Puzriakova Classified gene: AMOTL1 as Amber List (moderate evidence)
Clefting v4.79 AMOTL1 Arina Puzriakova Added comment: Comment on list classification: There is now sufficient evidence to rate this gene as Green at the next GMS panel update.

At least 16 individuals from 12 families have been identified with heterozygous variants in a AMOTL1 hotspot (PMIDs: 30375152; 33026150; 36751037). The most common clinical features were orofacial clefting (15/16; 94%), large and dysplastic ears (10/16; 62.5%), congenital heart disease (8/16; 50%), tall stature (7/16; 44%), hearing loss (5/16; 31%), liver disease (5/16; 31%), and neurodevelopmental disease (5/16; 31%).
Clefting v4.79 AMOTL1 Arina Puzriakova Gene: amotl1 has been classified as Amber List (Moderate Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.170 MASP1 Achchuthan Shanmugasundram reviewed gene: MASP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 33765348, 36980886; Phenotypes: 3MC syndrome 1, OMIM:257920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.90 ACAN Arina Puzriakova commented on gene: ACAN
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.170 KANSL1 Achchuthan Shanmugasundram reviewed gene: KANSL1: Rating: RED; Mode of pathogenicity: None; Publications: 26424144, 29093661, 36980886; Phenotypes: craniosynostosis, MONDO:0015469; Mode of inheritance: None
Childhood solid tumours v4.5 FBXW7 Arina Puzriakova Classified gene: FBXW7 as Amber List (moderate evidence)
Childhood solid tumours v4.5 FBXW7 Arina Puzriakova Added comment: Comment on list classification: Rating Amber as at present I do not think there is enough evidence to classify this as a diagnostic-grade cancer gene.

There are previous reports of dn/inh germline variants in individuals (likely 7) with tumor predisposition, two had structural alternations that affected other genomic regions and the others were identified from a targeted Wilms cohort.
FBXW7 heterozygous variants have also been associated with a neurodevelopmental disorder (OMIM:620012; G2P - moderate) but these individuals not shown malignancy. FBXW7 is not linked to a cancer phenotype in OMIM or G2P.
Nonetheless this is a tumour suppressor gene that is worth monitoring for new evidence linking to cancer susceptibility (added watchlist tag).
Childhood solid tumours v4.5 FBXW7 Arina Puzriakova Gene: fbxw7 has been classified as Amber List (Moderate Evidence).
Childhood solid tumours v4.4 FBXW7 Arina Puzriakova Phenotypes for gene: FBXW7 were changed from Developmental delay, hypotonia, and impaired language to Wilms tumor, MONDO:0006058; Rhabdoid tumor, MONDO:0002728
Childhood solid tumours v4.3 FBXW7 Arina Puzriakova Publications for gene: FBXW7 were set to 30885698
Childhood solid tumours v4.2 FBXW7 Arina Puzriakova Tag watchlist tag was added to gene: FBXW7.
Childhood solid tumours v4.2 FBXW7 Arina Puzriakova reviewed gene: FBXW7: Rating: ; Mode of pathogenicity: None; Publications: 19963109, 20332316, 26482194, 30885698; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Breast cancer pertinent cancer susceptibility v2.5 CDH1 Arina Puzriakova Publications for gene: CDH1 were set to 36436516
Breast cancer pertinent cancer susceptibility v2.4 CDH1 Arina Puzriakova Phenotypes for gene: CDH1 were changed from Lobular breast cancer to Diffuse gastric and lobular breast cancer syndrome with or without cleft lip and/or palate, OMIM:137215
Breast cancer pertinent cancer susceptibility v2.3 CDH1 Arina Puzriakova Tag Q3_23_promote_green tag was added to gene: CDH1.
Tag Q3_23_expert_review tag was added to gene: CDH1.
Breast cancer pertinent cancer susceptibility v2.3 CDH1 Arina Puzriakova Classified gene: CDH1 as Amber List (moderate evidence)
Breast cancer pertinent cancer susceptibility v2.3 CDH1 Arina Puzriakova Added comment: Comment on list classification: New gene added to this panel by Lauma Freimane. Germline heterozygous variants have been found in diffuse gastric and lobular breast cancer syndrome. Patients may develop lobular breast cancer only or lobular breast cancer with gastric cancer. Lobular carcinoma of the breast has been reported in up to 60% of female carriers.

Overall there is sufficient evidence to classify this as a breast cancer susceptibility gene. However, it should be noted that this gene is already covered by a targeted panel, R215 CDH1-related cancer syndrome. Will leave the decision with the GMS expert group as to whether this phenotype should also be covered by this panel.
Breast cancer pertinent cancer susceptibility v2.3 CDH1 Arina Puzriakova Gene: cdh1 has been classified as Amber List (Moderate Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.170 SCARF2 Achchuthan Shanmugasundram reviewed gene: SCARF2: Rating: RED; Mode of pathogenicity: None; Publications: 29168297, 29620724, 36980886; Phenotypes: Van den Ende-Gupta syndrome, OMIM:600920, craniosynostosis, MONDO:0015469; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.170 ZCCHC11 Achchuthan Shanmugasundram gene: ZCCHC11 was added
gene: ZCCHC11 was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: ZCCHC11 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ZCCHC11 were set to 28808027; 36980886
Phenotypes for gene: ZCCHC11 were set to craniosynostosis, MONDO:0015469
Review for gene: ZCCHC11 was set to RED
Added comment: An individual was described with metopic synostosis and a novel de novo frameshift variant in ZCCHC11 (p.Glu1275fs) (PMID:28808027).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.169 ZBTB20 Achchuthan Shanmugasundram gene: ZBTB20 was added
gene: ZBTB20 was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: ZBTB20 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZBTB20 were set to 34429528; 36980886
Phenotypes for gene: ZBTB20 were set to Primrose syndrome, OMIM:259050; craniosynostosis, MONDO:0015469
Review for gene: ZBTB20 was set to RED
Added comment: A de novo missense variant (c.1948A>C; p.Asn650His) was identified in an individual from the 100k genomes project with craniosynostosis, congenital heart disease, intellectual disability, and spinal anomalies (PMID:34429528).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.168 TWIST2 Achchuthan Shanmugasundram Publications for gene: TWIST2 were set to
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.167 TWIST2 Achchuthan Shanmugasundram Mode of inheritance for gene: TWIST2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.166 TWIST2 Achchuthan Shanmugasundram reviewed gene: TWIST2: Rating: RED; Mode of pathogenicity: None; Publications: 31292255, 36980886; Phenotypes: craniosynostosis, MONDO:0015469; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.166 TMEM251 Achchuthan Shanmugasundram gene: TMEM251 was added
gene: TMEM251 was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: TMEM251 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM251 were set to 33252156; 36980886
Phenotypes for gene: TMEM251 were set to Dysostosis multiplex, Ain-Naz type, OMIM:619345; craniosynostosis, MONDO:0015469
Review for gene: TMEM251 was set to RED
Added comment: Whole-exome sequencing identified two homozygous variants c.133C>T/ p.Arg45Trp (absent from gnomAD) and c.215dupA/ p.Tyr72Ter (2 alleles in gnomAD, annotated as pathogenic in ClinVar), in two families. Immunofluorescence and confocal studies show that the p.Arg45Trp mutant TMEM251 protein was targeted less efficiently to the Golgi complex compared to wildtype protein (PMID:33252156).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.165 SRCAP Achchuthan Shanmugasundram gene: SRCAP was added
gene: SRCAP was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: SRCAP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SRCAP were set to 33288889; 36980886
Review for gene: SRCAP was set to RED
Added comment: One individual was described with a stop-gain variant in SRCAP (c.7303C>T; p.Arg2435Ter) in the Norwegian cohort (PMID:33288889).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.164 SPRY4 Achchuthan Shanmugasundram gene: SPRY4 was added
gene: SPRY4 was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: SPRY4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SPRY4 were set to 28808027; 36980886
Phenotypes for gene: SPRY4 were set to craniosynostosis, MONDO:0015469
Review for gene: SPRY4 was set to RED
Added comment: An individual was described with a heterozygous de novo variant in SPRY4 (p.Glu160Ter) (PMID:28808027). This gene has a low pLI (0) suggesting tolerance to loss-of-function.
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.163 SP7 Achchuthan Shanmugasundram gene: SP7 was added
gene: SP7 was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: SP7 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SP7 were set to 35121733; 36980886
Phenotypes for gene: SP7 were set to craniosynostosis, MONDO:0015469
Review for gene: SP7 was set to RED
Added comment: A de novo missense variant (c.926 C>G; p.Ser309Trp) in SP7 was identified in a patient with craniosynostosis, cranial hyperostosis, and long bone fragility. Mice with the corresponding variant also show a complex skeletal phenotype distinct from that of Sp7-null mice (PMID:35121733).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.162 SMURF1 Achchuthan Shanmugasundram changed review comment from: An individual was described with metopic synostosis and a de novo variant in SMURF1 (p.Arg468Trp) (PMID:28808027)
Sources: Literature; to: An individual was described with metopic synostosis and a de novo variant in SMURF1 (p.Arg468Trp) (PMID:28808027).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.162 SMURF1 Achchuthan Shanmugasundram gene: SMURF1 was added
gene: SMURF1 was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: SMURF1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SMURF1 were set to 28808027; 36980886
Phenotypes for gene: SMURF1 were set to craniosynostosis, MONDO:0015469
Review for gene: SMURF1 was set to RED
Added comment: An individual was described with metopic synostosis and a de novo variant in SMURF1 (p.Arg468Trp) (PMID:28808027)
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.161 SMC1A Achchuthan Shanmugasundram gene: SMC1A was added
gene: SMC1A was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: SMC1A was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: SMC1A were set to 29037998; 36980886
Phenotypes for gene: SMC1A were set to Cornelia de Lange syndrome 2, OMIM:300590; craniosynostosis, MONDO:0015469
Review for gene: SMC1A was set to RED
Added comment: An X-linked dominant variant (c.3581A>G; p.Tyr1194Cys) was identified in an individual with Cornelia de Lange syndrome (characterised by dysmorphic facial features, growth, and developmental delay and syndromic craniosynostosis). Their mother was mosaic for the variant (PMID:29037998).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.160 SMARCD2 Achchuthan Shanmugasundram gene: SMARCD2 was added
gene: SMARCD2 was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: SMARCD2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SMARCD2 were set to 28808027; 36980886
Phenotypes for gene: SMARCD2 were set to craniosynostosis, MONDO:0015469
Review for gene: SMARCD2 was set to RED
Added comment: An individual was described with metopic synostosis and a de novo variant in SMARCD2 (p.Arg73Ter) (PMID:28808027).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.159 SMAD2 Achchuthan Shanmugasundram gene: SMAD2 was added
gene: SMAD2 was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: SMAD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMAD2 were set to 34429528; 36980886
Phenotypes for gene: SMAD2 were set to Loeys-Dietz syndrome 6, OMIM:619656
Review for gene: SMAD2 was set to RED
Added comment: A de novo variant in SMAD2 (c.1223T>C; p.Leu408Pro) was identified in an individual within the craniosynostosis cohort of the 100k genomes project. The variant was absent from gnomAD and was predicted to affect a residue within a functional domain (PMID:34429528).
Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v4.22 EZR Boaz Palterer gene: EZR was added
gene: EZR was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: EZR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EZR were set to 37301410
Phenotypes for gene: EZR were set to hypogammaglobulinemia; immunodeficiency
Penetrance for gene: EZR were set to unknown
Review for gene: EZR was set to RED
Added comment: One kindred with 1 affected subject (homozygous EZR p.A129T), disease segregates with the variant. Extensive functional analysis.
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.158 SIX2 Achchuthan Shanmugasundram gene: SIX2 was added
gene: SIX2 was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: SIX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SIX2 were set to 26581443; 36980886
Phenotypes for gene: SIX2 were set to six2-related frontonasal dysplasia, MONDO:0044628; craniosynostosis, MONDO:0015469
Review for gene: SIX2 was set to RED
Added comment: A family with a dominantly inherited craniofacial phenotype (frontal bossing with high hairline, ptosis, hypertelorism, broad nasal tip, large anterior fontanelle, cranial base anomalies, and sagittal synostosis (only confirmed in one individual)) were identified on chromosomal microarray to harbour a heterozygous 108.3 kilobase deletion of chromosome 2p21 (disrupting SIX2 and the surround non-coding DNA) (PMID:26581443).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.157 SH3BP4 Achchuthan Shanmugasundram gene: SH3BP4 was added
gene: SH3BP4 was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: SH3BP4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SH3BP4 were set to 35080095; 36980886
Phenotypes for gene: SH3BP4 were set to craniosynostosis, MONDO:0015469
Review for gene: SH3BP4 was set to RED
Added comment: A patient was described with a recessive variant in SH3BP4 (c.128C>A; p.Pro43His) in the Norwegian craniosynostosis cohort. The variant has a CADD score of 33 and a gnomAD allele frequency of 9.6 x 10-5 (no homozygotes are reported in gnomAD). The patient presented with a Chiari I malformation, exophthalmos, eating difficulties as an infant, microcephaly, recurrent infections, dysmorphic features, Kabuki-like syndrome, and pan-synostosis. This patient also harbours two variants in KMT2D: c.11599C>A; p.Gln3867Lys (CADD = 22) and c.7182C>A; p.Ser2394Arg (CADD = 20); gnomAD frequency 1.2 x 10-5 and absent, respectively (PMID:35080095).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.156 SCN8A Achchuthan Shanmugasundram changed review comment from: A heterozygous duplication involving SCN8A was identified in an individual with hearing impairment, hypermobility, intellectual disability, ventricular septal defect and craniosynostosis (c.3924dup; p.Arg1309Thrfs*3) (PMID:34429528)
Sources: Literature; to: A heterozygous duplication involving SCN8A was identified in an individual with hearing impairment, hypermobility, intellectual disability, ventricular septal defect and craniosynostosis (c.3924dup; p.Arg1309Thrfs*3) (PMID:34429528).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.156 SCN8A Achchuthan Shanmugasundram gene: SCN8A was added
gene: SCN8A was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: SCN8A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SCN8A were set to 34429528; 36980886
Phenotypes for gene: SCN8A were set to craniosynostosis, MONDO:0015469
Review for gene: SCN8A was set to RED
Added comment: A heterozygous duplication involving SCN8A was identified in an individual with hearing impairment, hypermobility, intellectual disability, ventricular septal defect and craniosynostosis (c.3924dup; p.Arg1309Thrfs*3) (PMID:34429528)
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.155 RASAL2 Achchuthan Shanmugasundram gene: RASAL2 was added
gene: RASAL2 was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: RASAL2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RASAL2 were set to 28808027; 36980886
Phenotypes for gene: RASAL2 were set to craniosynostosis, MONDO:0015469
Review for gene: RASAL2 was set to RED
Added comment: An individual was described with sagittal synostosis and a de novo variant in RASAL2 (p.Arg571Pro) (PMID:28808027)
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.154 PUF60 Achchuthan Shanmugasundram gene: PUF60 was added
gene: PUF60 was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: PUF60 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PUF60 were set to 36367278; 36980886
Phenotypes for gene: PUF60 were set to craniosynostosis, MONDO:0015469
Review for gene: PUF60 was set to RED
Added comment: A patient presenting with Verheij syndrome, characterised by craniofacial dysmorphism, multiple congenital anomalies and variable neurodevelopmental delay, was identified with a heterozygous variant in the splicing factor PUF60 (c.436C>T; p.Arg146Cys). They displayed fusion of the coronal and sagittal suture (PMID:36367278).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.153 PTH2R Achchuthan Shanmugasundram gene: PTH2R was added
gene: PTH2R was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: PTH2R was set to Other
Publications for gene: PTH2R were set to 26044810; 36980886
Phenotypes for gene: PTH2R were set to craniosynostosis, MONDO:0015469
Review for gene: PTH2R was set to RED
Added comment: A boy presenting with sagittal and metopic synostosis was found to harbour a complex paracentric inversion involving 2q14.3 and 2q3. An intronic break of the PTH2R gene was
detected by whole genome sequencing and fluorescence in situ hybridisation (PMID:26044810).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.152 PSMD12 Achchuthan Shanmugasundram gene: PSMD12 was added
gene: PSMD12 was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: PSMD12 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PSMD12 were set to 34429528; 36980886
Phenotypes for gene: PSMD12 were set to craniosynostosis, MONDO:0015469
Review for gene: PSMD12 was set to RED
Added comment: A heterozygous variant was identified in the UK 100k genomes project (parents were not available for testing): c.1284G>A; p.Trp428* (PMID:34429528)
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.151 PSMC5 Achchuthan Shanmugasundram gene: PSMC5 was added
gene: PSMC5 was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: PSMC5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PSMC5 were set to 28808027; 36980886
Phenotypes for gene: PSMC5 were set to craniosynostosis, MONDO:0015469
Review for gene: PSMC5 was set to RED
Added comment: An individual was described with metopic synostosis and a de novo variant in PSMC5 (p.Arg317Trp) (PMID:28808027).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.150 PSMC2 Achchuthan Shanmugasundram gene: PSMC2 was added
gene: PSMC2 was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: PSMC2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PSMC2 were set to 28808027; 36980886
Phenotypes for gene: PSMC2 were set to craniosynostosis, MONDO:0015469
Review for gene: PSMC2 was set to RED
Added comment: An individual was described with metopic synostosis and a de novo variant in PSMC2 (p.Arg297Gly) (PMID:28808027).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.149 POLR2A Achchuthan Shanmugasundram gene: POLR2A was added
gene: POLR2A was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: POLR2A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: POLR2A were set to 35080095; 36980886
Phenotypes for gene: POLR2A were set to Neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities, OMIM:618603; craniosynostosis, MONDO:0015469
Review for gene: POLR2A was set to RED
Added comment: A de novo insertion was identified in the Norwegian sequencing study: c.4329_4330delinsAA; p.Ala1444Thr. The variant is absent from gnomAD (v.2.1.1) but is not predicted to affect a functional domain. The patient displayed metopic synostosis, impaired motor skills, hypospadias, hypermobile joints and hyperactive behaviour (PMID:35080095).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.148 PITX2 Achchuthan Shanmugasundram gene: PITX2 was added
gene: PITX2 was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: PITX2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PITX2 were set to 36980886
Review for gene: PITX2 was set to RED
Added comment: Tooze et al has reviewed in PMID:36980886 from unpublished data that two cases of de novo missense variants are known with craniosynostosis, but not reported.
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.147 OSTM1 Achchuthan Shanmugasundram Phenotypes for gene: OSTM1 were changed from AR osteopetrosis 5 to Osteopetrosis, autosomal recessive 5, OMIM:259720; craniosynostosis, MONDO:0015469
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.146 OSTM1 Achchuthan Shanmugasundram Publications for gene: OSTM1 were set to
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.145 OSTM1 Achchuthan Shanmugasundram Mode of inheritance for gene: OSTM1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.144 OSTM1 Achchuthan Shanmugasundram edited their review of gene: OSTM1: Changed phenotypes to: Osteopetrosis, autosomal recessive 5, OMIM:259720, craniosynostosis, MONDO:0015469
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.144 OSTM1 Achchuthan Shanmugasundram changed review comment from: An individual was reported with osteopetrosis, craniosynostosis, and Chiari malformation type 1 and two novel homozygous variants in OSTEM1. The first was a missense variant c.265T>A (p.Val122Asp), which was considered neutral. The second variant was a synonymous change (c.108C>T) but was predicted to create a new donor splice site and disrupt mRNA processing (PMID:23772242).; to: An individual was reported with osteopetrosis, craniosynostosis, and Chiari malformation type 1 and two novel homozygous variants in OSTEM1. The first was a missense variant c.265T>A (p.Val122Asp), which was considered neutral. The second variant was a synonymous change (c.108C>T) but was predicted to create a new donor splice site and disrupt mRNA processing (PMID:23772242).
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.144 OSTM1 Achchuthan Shanmugasundram reviewed gene: OSTM1: Rating: RED; Mode of pathogenicity: None; Publications: 23772242, 36980886; Phenotypes: craniosynostosis, MONDO:0015469; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.144 NTRK2 Achchuthan Shanmugasundram gene: NTRK2 was added
gene: NTRK2 was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: NTRK2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NTRK2 were set to 27884935; 36980886
Phenotypes for gene: NTRK2 were set to Obesity, hyperphagia, and developmental delay, OMIM:613886; craniosynostosis, MONDO:0015469
Review for gene: NTRK2 was set to RED
Added comment: A heterozygous stop-gain variant was identified in an individual with unicoronal synostosis, language delay, hyperphagic obesity, and aggression (c.1330G>T; p.Gly444*). It was suspected that the variant arose de novo but the father’s sample was not available for testing (PMID:27884935).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.143 NAA25 Achchuthan Shanmugasundram gene: NAA25 was added
gene: NAA25 was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: NAA25 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NAA25 were set to 30152016; 36980886
Phenotypes for gene: NAA25 were set to craniosynostosis, MONDO:0015469
Review for gene: NAA25 was set to RED
Added comment: One individual was described with sagittal synostosis to harbour a de novo frameshifting variant in NAA25 (p.Phe359fs*) (PMID:30152016).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.142 MMP21 Achchuthan Shanmugasundram gene: MMP21 was added
gene: MMP21 was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: MMP21 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MMP21 were set to 34429528; 36980886
Phenotypes for gene: MMP21 were set to craniosynostosis, MONDO:0015469
Review for gene: MMP21 was set to RED
Added comment: Compound heterozygous variants (c.671_684del/ p.Val224Glyfs*29 and c.775C>G/ p.His259Asp) were identified in an individual within the 100kGP with heterotaxy and craniosynostosis (PMID:34429528)
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.141 MED13L Achchuthan Shanmugasundram gene: MED13L was added
gene: MED13L was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: MED13L was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MED13L were set to 28371282; 36980886
Phenotypes for gene: MED13L were set to Impaired intellectual development and distinctive facial features with or without cardiac defects, OMIM:616789; craniosynostosis, MONDO:0015469
Review for gene: MED13L was set to RED
Added comment: Two siblings exhibited an intragenic deletion of exons 3-14 resulting in MED13L haploinsufficiency syndrome (intellectual disability, developmental delay, heart defects and dysmorphic features). The deletion was inherited from their mother who showed low frequency mosaicism. The older sibling also presented with craniosynostosis (PMID:28371282).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.140 MACF1 Achchuthan Shanmugasundram gene: MACF1 was added
gene: MACF1 was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: MACF1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MACF1 were set to 28808027; 36980886
Phenotypes for gene: MACF1 were set to craniosynostosis, MONDO:0015469
Review for gene: MACF1 was set to RED
Added comment: An individual was described with sagittal synostosis and a novel splicing variant in MACF1 (IVS89+1G>A) (PMID:28808027).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.139 KPTN Achchuthan Shanmugasundram Classified gene: KPTN as Amber List (moderate evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.139 KPTN Achchuthan Shanmugasundram Gene: kptn has been classified as Amber List (Moderate Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.138 KPTN Achchuthan Shanmugasundram gene: KPTN was added
gene: KPTN was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: KPTN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KPTN were set to 24239382; 36980886
Phenotypes for gene: KPTN were set to Intellectual developmental disorder, autosomal recessive 41, OMIM:615637; craniosynostosis, MONDO:0015469
Review for gene: KPTN was set to AMBER
Added comment: Four families were described with variants in KPTN and suspected craniosynostosis. Sagittal synostosis was confirmed in one individual from a family with three affected individuals. All families harboured a variant encoding p.Ser259*; this was homozygous in four individuals and in trans with another heterozygous variant (p.Met241_Gln246dup) in five individuals (PMID:24239382).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.137 KMT5B Achchuthan Shanmugasundram gene: KMT5B was added
gene: KMT5B was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: KMT5B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KMT5B were set to 34429528; 36980886
Phenotypes for gene: KMT5B were set to craniosynostosis, MONDO:0015469
Review for gene: KMT5B was set to RED
Added comment: A de novo loss of function variant was identified within the 100kGP craniosynostosis cohort: c.557T>A; p.Leu186* (PMID:34429528).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.136 IFRD1 Achchuthan Shanmugasundram gene: IFRD1 was added
gene: IFRD1 was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: IFRD1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: IFRD1 were set to 35997807; 36980886
Phenotypes for gene: IFRD1 were set to craniosynostosis, MONDO:0015469
Review for gene: IFRD1 was set to RED
Added comment: A de novo variant was identified in a cohort of patients with lambdoid synostosis (p.Gly6fs*) (PMID:35997807).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.135 HIST1H1E Achchuthan Shanmugasundram gene: HIST1H1E was added
gene: HIST1H1E was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
new-gene-name tags were added to gene: HIST1H1E.
Mode of inheritance for gene: HIST1H1E was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: HIST1H1E were set to 36118902; 36980886
Phenotypes for gene: HIST1H1E were set to craniosynostosis, MONDO:0015469
Review for gene: HIST1H1E was set to RED
Added comment: A patient with syndromic unilambdoid synostosis was found to harbour a frameshifting variant in HIST1H1E (c.433_434insC; p.Thr146Hisfs*50). The variant is reported as pathogenic for Rahman syndrome in ClinVar and absent from gnomAD (PMID:36118902).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.134 HDAC4 Achchuthan Shanmugasundram gene: HDAC4 was added
gene: HDAC4 was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
cnv tags were added to gene: HDAC4.
Mode of inheritance for gene: HDAC4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HDAC4 were set to 33288889; 36980886
Phenotypes for gene: HDAC4 were set to craniosynostosis, MONDO:0015469
Review for gene: HDAC4 was set to RED
Added comment: A patient was described with two copy number variants: g.233110452_ 243028452 and del g.210300_ 8664358dup. The second variant was maternally inherited (PMID:33288889)
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.133 H3F3B Achchuthan Shanmugasundram gene: H3F3B was added
gene: H3F3B was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: H3F3B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: H3F3B were set to 33268356; 36980886
Phenotypes for gene: H3F3B were set to craniosynostosis, MONDO:0015469
Review for gene: H3F3B was set to RED
Added comment: In a cohort of 33 patients with H3F3A variants and 13 patients with H3F3B variants, 5/13 (~40%) individuals with H3F3B variants were reported with “craniosynostosis or abnormal head shape”. Of these, it is not clear if these were radiologically confirmed and what proportion of this subset of patients had synostosis compared to dysmorphic features (PMID:33268356).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.132 H3F3A Achchuthan Shanmugasundram gene: H3F3A was added
gene: H3F3A was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: H3F3A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: H3F3A were set to 33268356; 36980886
Phenotypes for gene: H3F3A were set to craniosynostosis, MONDO:0015469
Review for gene: H3F3A was set to RED
Added comment: In a cohort of 33 patients with H3F3A variants and 13 patients with H3F3B variants, 9/33 (~30%) individuals with H3F3A variants were reported with “craniosynostosis or abnormal head shape”. Of these, it is not clear if these were radiologically confirmed and what proportion of this subset of patients had synostosis compared to dysmorphic features (PMID:33268356).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.131 GLIS3 Achchuthan Shanmugasundram gene: GLIS3 was added
gene: GLIS3 was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: GLIS3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GLIS3 were set to 26259131; 36980886
Phenotypes for gene: GLIS3 were set to craniosynostosis, MONDO:0015469
Review for gene: GLIS3 was set to RED
Added comment: One patient was described with a variant in GLIS3 and sagittal craniosynostosis requiring surgical intervention. The patient harboured a homozygous deletion of exons 9 – 11; consanguinity was not confirmed but suspected (PMID:26259131).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.130 GPC4 Achchuthan Shanmugasundram gene: GPC4 was added
gene: GPC4 was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: GPC4 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: GPC4 were set to 31292255; 36980886
Phenotypes for gene: GPC4 were set to craniosynostosis, MONDO:0015469
Review for gene: GPC4 was set to RED
Added comment: A variant in GPC4 was identified in an individual with syndromic craniosynostosis. The variant encoding p.Val152fs arose de novo in the mother (PMID:31292255)
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.129 GLI2 Achchuthan Shanmugasundram gene: GLI2 was added
gene: GLI2 was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: GLI2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: GLI2 were set to 31292255; 36980886
Phenotypes for gene: GLI2 were set to craniosynostosis, MONDO:0015469
Review for gene: GLI2 was set to RED
Added comment: A de novo GLI2 variant (p.Ala551Thr) was identified in an individual with syndromic craniosynostosis (PMID:31292255).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.128 FUZ Achchuthan Shanmugasundram gene: FUZ was added
gene: FUZ was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: FUZ was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FUZ were set to 34719684; 36980886
Phenotypes for gene: FUZ were set to craniosynostosis, MONDO:0015469
Review for gene: FUZ was set to RED
Added comment: A pair of monozygotic twins were described with craniosynostosis and a novel variant in FUZ (c.851G>C; p.Arg284Pro) (PMID:34719684).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.127 FTO Achchuthan Shanmugasundram gene: FTO was added
gene: FTO was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: FTO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FTO were set to 26697951; 36980886
Phenotypes for gene: FTO were set to craniosynostosis, MONDO:0015469
Review for gene: FTO was set to RED
Added comment: A homozygous variant in FTO (c.956G>A; p.Arg322Gln) was described in one individual with multiple malformation syndrome, which included craniosynostosis. Craniosynostosis is not a consistent feature of variants in FTO (PMID:26697951).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.126 FOXO1 Achchuthan Shanmugasundram gene: FOXO1 was added
gene: FOXO1 was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: FOXO1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FOXO1 were set to 35997807; 36980886
Phenotypes for gene: FOXO1 were set to craniosynostosis, MONDO:0015469
Review for gene: FOXO1 was set to RED
Added comment: PMID:35997807 reported a cohort of patients with lambdoid synostosis, where a de novo variant (p.Arg180Trp) was identified in FOXO1. Hence, this gene should be added with a red rating.
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.125 FOXP2 Achchuthan Shanmugasundram gene: FOXP2 was added
gene: FOXP2 was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: FOXP2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FOXP2 were set to 35080095; 36980886
Phenotypes for gene: FOXP2 were set to craniosynostosis, MONDO:0015469
Review for gene: FOXP2 was set to RED
Added comment: A familial variant in FOXP2 (c.484del; p.Gln162fs) was identified in individuals with developmental delay, hypermetropia, orofacial dyspraxia and sagittal craniosynostosis. The variant is absent from gnomAD (PMID:35080095)
Sources: Literature
Paediatric disorders - additional genes v3.3 FOXL2 Arina Puzriakova commented on gene: FOXL2: Helen Brittain (Genomics England Clinical Team) supports inclusion of BPES and blepharophimosis genes on this panel as these are features that would be considered under the dysmorphism indication.
Limb disorders v4.7 ISCA-37467-Gain Arina Puzriakova changed review comment from: Comment on list classification: Adding to this panel under the suggestion of Helen Brittain (Genomics England Clinical Team) as this region is associated with limb malformation phenotypes. Enough evidence to rate this gene as Green at the next GMS panel update.; to: Comment on list classification: Adding to this panel under the suggestion of Helen Brittain (Genomics England Clinical Team) as this region is associated with limb malformation phenotypes. Enough evidence to rate as Green at the next GMS panel update.
Limb disorders v4.7 ISCA-37467-Gain Arina Puzriakova Tag Q3_23_promote_green tag was added to Region: ISCA-37467-Gain.
Limb disorders v4.7 ISCA-37467-Gain Arina Puzriakova Classified Region: ISCA-37467-Gain as Amber List (moderate evidence)
Limb disorders v4.7 ISCA-37467-Gain Arina Puzriakova Added comment: Comment on list classification: Adding to this panel under the suggestion of Helen Brittain (Genomics England Clinical Team) as this region is associated with limb malformation phenotypes. Enough evidence to rate this gene as Green at the next GMS panel update.
Limb disorders v4.7 ISCA-37467-Gain Arina Puzriakova Region: isca-37467-gain has been classified as Amber List (Moderate Evidence).
Limb disorders v4.6 ISCA-37467-Gain Arina Puzriakova Deleted their comment
Limb disorders v4.6 ISCA-37467-Gain Arina Puzriakova Entity copied from Clefting v4.78
Limb disorders v4.6 ISCA-37467-Gain Arina Puzriakova Region: ISCA-37467-Gain was added
Region: ISCA-37467-Gain was added to Limb disorders. Sources: ClinGen,Expert Review Green
Mode of inheritance for Region: ISCA-37467-Gain was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for Region: ISCA-37467-Gain were set to 19291772; 18417549; 18178630
Phenotypes for Region: ISCA-37467-Gain were set to human triphalangeal thumb and polysyndactyly (TPT-PS) phenotype; 174500; Triphalangeal thumbpolysyndactyly syndrome; syndactyly type IV with tibial hypoplasia
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.124 FOXP1 Achchuthan Shanmugasundram gene: FOXP1 was added
gene: FOXP1 was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: FOXP1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FOXP1 were set to 29330474; 36980886
Phenotypes for gene: FOXP1 were set to craniosynostosis, MONDO:0015469
Review for gene: FOXP1 was set to RED
Added comment: Whole exome sequencing identified a de novo splicing variant in FOXP1 (c.1428+1 G>A; p.Ala450GLyfs*13) in a patient with syndromic intellectual disability and trigonocephaly (PMID:29330474).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.123 EXTL3 Achchuthan Shanmugasundram changed review comment from: A recessive variant in EXTL3 (c.2392G>A; p.Val798Met) was identified in a patient with metopic craniosynostosis, intellectual disability, short stature, microcephaly, hip dysplasia, kyphosis, delayed skeletal age and immunodeficiency. The variant is absent from gnomAD and affects the glycosyl transferase family 64 domain (PMID:35080095).

Craniosynostosis has been recorded as part of the phenotype in OMIM (MIM #617425)
Sources: Literature; to: A recessive variant in EXTL3 (c.2392G>A; p.Val798Met) was identified in a patient with metopic craniosynostosis, intellectual disability, short stature, microcephaly, hip dysplasia, kyphosis, delayed skeletal age and immunodeficiency. The variant is absent from gnomAD and affects the glycosyl transferase family 64 domain (PMID:35080095).

Craniosynostosis has been recorded as part of the phenotype in OMIM (MIM #617425).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.123 EXTL3 Achchuthan Shanmugasundram changed review comment from: A recessive variant in EXTL3 (c.2392G>A; p.Val798Met) was identified in a patient with metopic craniosynostosis, intellectual disability, short stature, microcephaly, hip dysplasia, kyphosis, delayed skeletal age and immunodeficiency. The variant is absent from gnomAD and affects the glycosyl transferase family 64 domain (PMID:35080095).
Sources: Literature; to: A recessive variant in EXTL3 (c.2392G>A; p.Val798Met) was identified in a patient with metopic craniosynostosis, intellectual disability, short stature, microcephaly, hip dysplasia, kyphosis, delayed skeletal age and immunodeficiency. The variant is absent from gnomAD and affects the glycosyl transferase family 64 domain (PMID:35080095).

Craniosynostosis has been recorded as part of the phenotype in OMIM (MIM #617425)
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.123 EXTL3 Achchuthan Shanmugasundram edited their review of gene: EXTL3: Changed phenotypes to: Immunoskeletal dysplasia with neurodevelopmental abnormalities, OMIM:617425
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.123 EXTL3 Achchuthan Shanmugasundram Phenotypes for gene: EXTL3 were changed from craniosynostosis, MONDO:0015469 to Immunoskeletal dysplasia with neurodevelopmental abnormalities, OMIM:617425
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.122 EXTL3 Achchuthan Shanmugasundram gene: EXTL3 was added
gene: EXTL3 was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: EXTL3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXTL3 were set to 35080095; 36980886
Phenotypes for gene: EXTL3 were set to craniosynostosis, MONDO:0015469
Review for gene: EXTL3 was set to RED
Added comment: A recessive variant in EXTL3 (c.2392G>A; p.Val798Met) was identified in a patient with metopic craniosynostosis, intellectual disability, short stature, microcephaly, hip dysplasia, kyphosis, delayed skeletal age and immunodeficiency. The variant is absent from gnomAD and affects the glycosyl transferase family 64 domain (PMID:35080095).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.121 EIF5A Achchuthan Shanmugasundram gene: EIF5A was added
gene: EIF5A was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: EIF5A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: EIF5A were set to 36118902; 36980886
Phenotypes for gene: EIF5A were set to craniosynostosis, MONDO:0015469
Review for gene: EIF5A was set to RED
Added comment: An intronic variant was identified in EIF5A (c.271-1G>C) within the Chinese cohort in a patient with metopic synostosis (PMID:36118902).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.120 EHMT1 Achchuthan Shanmugasundram gene: EHMT1 was added
gene: EHMT1 was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: EHMT1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: EHMT1 were set to 33288889; 36980886
Phenotypes for gene: EHMT1 were set to craniosynostosis, MONDO:0015469
Review for gene: EHMT1 was set to RED
Added comment: A de novo splicing variant was identified in EHMT1 (c.2018+1G>C) within the Norwegian cohort with syndromic craniosynostosis (PMID:33288889).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.119 DVL3 Achchuthan Shanmugasundram gene: DVL3 was added
gene: DVL3 was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: DVL3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DVL3 were set to 28808027; 36980886
Phenotypes for gene: DVL3 were set to craniosynostosis, MONDO:0015469
Review for gene: DVL3 was set to RED
Added comment: An individual was described with sagittal synostosis and a de novo variant in DVL3 (p.Gly327fs*) (PMID:28808027).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.118 DDX3X Achchuthan Shanmugasundram changed review comment from: A novel de novo missense variant was identified in the DDX3X gene (c.625C>G) by whole exome sequencing in a child with craniofacial dysmorphisms: brachycephaly and a flattened triangular-asymmetrical face characterized by micrognathia, mild hypertelorism, wide and prominent nose, short philtrum, thin lips and macroglossia (PMID:33789733).

Exome-sequencing identified three distinct de novo heterozygous variants in DDX3X: c.1511G>A; p.(Gly504Glu) (Patient 1), c.1436_1439delinsTCTC; p.(Asp479Arg480delinsValSer) (Patient 2), and c.641_643delTCA; p.(Ile214del) (Patient 3). The patients showed severe intellectual disability/developmental disorders, microcephaly, and dysmorphic features. Plagiocephaly was observed in Patient 1 and Patient 2 was diagnosed with sensorineural hearing loss and trigonocephaly. However, craniosynostosis was only radiologically confirmed in Patient 2 (PMID:30936465).

A de novo variant in DDX3X was identified in an additional patient with trigonocephaly, delay in speech acquisition and motor developmental delay: c.1616-2A>G; p.(?) (PMID:32530565).
Sources: Literature; to: A novel de novo missense variant was identified in the DDX3X gene (c.625C>G) by whole exome sequencing in a child with craniofacial dysmorphisms: brachycephaly and a flattened triangular-asymmetrical face characterized by micrognathia, mild hypertelorism, wide and prominent nose, short philtrum, thin lips and macroglossia (PMID:33789733).

Exome-sequencing identified three distinct de novo heterozygous variants in DDX3X: c.1511G>A; p.(Gly504Glu) (Patient 1), c.1436_1439delinsTCTC; p.(Asp479Arg480delinsValSer) (Patient 2), and c.641_643delTCA; p.(Ile214del) (Patient 3). The patients showed severe intellectual disability/developmental disorders, microcephaly, and dysmorphic features. Plagiocephaly was observed in Patient 1 and Patient 2 was diagnosed with sensorineural hearing loss and trigonocephaly. However, craniosynostosis was only radiologically confirmed in Patient 2 (PMID:30936465).

A de novo variant in DDX3X was identified in an additional patient with trigonocephaly, delay in speech acquisition and motor developmental delay: c.1616-2A>G (PMID:32530565).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.118 DDX3X Achchuthan Shanmugasundram Classified gene: DDX3X as Amber List (moderate evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.118 DDX3X Achchuthan Shanmugasundram Added comment: Comment on list classification: Although there are five unrelated cases reported with DDX3X variants and likely craniosynostosis, only two are radiologically confirmed cases of craniosynostosis. Hence, this gene should be rated amber.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.118 DDX3X Achchuthan Shanmugasundram Gene: ddx3x has been classified as Amber List (Moderate Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.117 DDX3X Achchuthan Shanmugasundram Phenotypes for gene: DDX3X were changed from craniosynostosis, MONDO:0015469 to Intellectual developmental disorder, X-linked syndromic, Snijders Blok type, OMIM:300958; craniosynostosis, MONDO:0015469
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.116 DDX3X Achchuthan Shanmugasundram edited their review of gene: DDX3X: Changed phenotypes to: Intellectual developmental disorder, X-linked syndromic, Snijders Blok type, OMIM:300958, craniosynostosis, MONDO:0015469
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.116 DDX3X Achchuthan Shanmugasundram gene: DDX3X was added
gene: DDX3X was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: DDX3X was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: DDX3X were set to 30936465; 32530565; 33789733; 36980886
Phenotypes for gene: DDX3X were set to craniosynostosis, MONDO:0015469
Review for gene: DDX3X was set to AMBER
Added comment: A novel de novo missense variant was identified in the DDX3X gene (c.625C>G) by whole exome sequencing in a child with craniofacial dysmorphisms: brachycephaly and a flattened triangular-asymmetrical face characterized by micrognathia, mild hypertelorism, wide and prominent nose, short philtrum, thin lips and macroglossia (PMID:33789733).

Exome-sequencing identified three distinct de novo heterozygous variants in DDX3X: c.1511G>A; p.(Gly504Glu) (Patient 1), c.1436_1439delinsTCTC; p.(Asp479Arg480delinsValSer) (Patient 2), and c.641_643delTCA; p.(Ile214del) (Patient 3). The patients showed severe intellectual disability/developmental disorders, microcephaly, and dysmorphic features. Plagiocephaly was observed in Patient 1 and Patient 2 was diagnosed with sensorineural hearing loss and trigonocephaly. However, craniosynostosis was only radiologically confirmed in Patient 2 (PMID:30936465).

A de novo variant in DDX3X was identified in an additional patient with trigonocephaly, delay in speech acquisition and motor developmental delay: c.1616-2A>G; p.(?) (PMID:32530565).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.115 CTNNA1 Achchuthan Shanmugasundram gene: CTNNA1 was added
gene: CTNNA1 was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: CTNNA1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CTNNA1 were set to 31292255; 36980886
Phenotypes for gene: CTNNA1 were set to craniosynostosis, MONDO:0015469
Review for gene: CTNNA1 was set to RED
Added comment: A de novo insertion (p.Val374_375ins) was identified in an individual from a screen of patients with syndromic craniosynostosis. This patient had sagittal craniosynostosis (PMID:31292255).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.114 COL11A1 Achchuthan Shanmugasundram gene: COL11A1 was added
gene: COL11A1 was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: COL11A1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: COL11A1 were set to 34429528; 36980886
Phenotypes for gene: COL11A1 were set to craniosynostosis, MONDO:0015469
Review for gene: COL11A1 was set to RED
Added comment: A de novo loss of function variant (c.2852+5G>A) was identified in an individual with craniosynostosis and a hearing impairment from the UK 100k genomes project (PMID:34429528)
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.113 CHD3 Achchuthan Shanmugasundram gene: CHD3 was added
gene: CHD3 was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: CHD3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CHD3 were set to 30397230; 36980886
Phenotypes for gene: CHD3 were set to craniosynostosis, MONDO:0015469
Review for gene: CHD3 was set to RED
Added comment: One of 35 individuals identified with Snijders Blok Campeau syndrome (neurodevelopmental disorder, macrocephaly and impaired speech and language) and with monoallelic variants in CHD3 gene (c.3482A>G; p.His1161Arg) presented with sagittal synostosis (PMID:30397230).

In addition, one of 28 patients with sequence variants (c.52_53inv; p.Ser18Glu) in the DECIPHER database (https://www.deciphergenomics.org/) was reported with craniosynostosis as one of the phenotypes./
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.112 CDK8 Achchuthan Shanmugasundram gene: CDK8 was added
gene: CDK8 was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: CDK8 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CDK8 were set to 30905399; 36980886
Phenotypes for gene: CDK8 were set to craniosynostosis, MONDO:0015469
Review for gene: CDK8 was set to RED
Added comment: Metopic synostosis was described in one individual out of 12 reported with variants in CDK8 from PMID:30905399. This individual harboured a de novo c.88G>A (p.Gly30Ser) variant.
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.111 CACNA1E Achchuthan Shanmugasundram Phenotypes for gene: CACNA1E were changed from crannieynostosis, MONDO:0015469s to craniosynostosis, MONDO:0015469
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.110 CACNA1E Achchuthan Shanmugasundram edited their review of gene: CACNA1E: Changed phenotypes to: craniosynostosis, MONDO:0015469
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.110 CACNA1E Achchuthan Shanmugasundram gene: CACNA1E was added
gene: CACNA1E was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: CACNA1E was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CACNA1E were set to 32530565; 36980886
Phenotypes for gene: CACNA1E were set to crannieynostosis, MONDO:0015469s
Review for gene: CACNA1E was set to RED
Added comment: A heterozygous splice variant (c.3674+5A>G) was identified in an individual from a cohort of patients with trigonocephaly (PMID:32530565).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.109 BRWD3 Achchuthan Shanmugasundram changed review comment from: A de novo stop-gain variant (p.Gln1338*) was identified in an individual with craniosynostosis within the 100k genomes project cohort (PMID:34429528). In addition, one of 20 patients with sequence variants in BRWD3 gene from DECIPHER database (https://www.deciphergenomics.org/) was reported with craniosynostosis as one of the phenotypes.
Sources: Literature; to: A de novo stop-gain variant (p.Gln1338*) was identified in an individual with craniosynostosis within the 100k genomes project cohort (PMID:34429528). In addition, one of 20 patients with sequence variants in BRWD3 gene (p.Gly707Val) from DECIPHER database (https://www.deciphergenomics.org/) was reported with craniosynostosis as one of the phenotypes.
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.109 BRWD3 Achchuthan Shanmugasundram Phenotypes for gene: BRWD3 were changed from to craniosynostosis, MONDO:0015469
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.108 BRWD3 Achchuthan Shanmugasundram edited their review of gene: BRWD3: Changed phenotypes to: craniosynostosis, MONDO:0015469
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.108 BRWD3 Achchuthan Shanmugasundram gene: BRWD3 was added
gene: BRWD3 was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: BRWD3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: BRWD3 were set to 34429528; 36980886
Review for gene: BRWD3 was set to RED
Added comment: A de novo stop-gain variant (p.Gln1338*) was identified in an individual with craniosynostosis within the 100k genomes project cohort (PMID:34429528). In addition, one of 20 patients with sequence variants in BRWD3 gene from DECIPHER database (https://www.deciphergenomics.org/) was reported with craniosynostosis as one of the phenotypes.
Sources: Literature
Nephrocalcinosis or nephrolithiasis v4.1 SLC26A1 Detlef Bockenhauer reviewed gene: SLC26A1: Rating: RED; Mode of pathogenicity: None; Publications: 36719378; Phenotypes: hyperoxaluria; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.107 AXIN1 Achchuthan Shanmugasundram gene: AXIN1 was added
gene: AXIN1 was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: AXIN1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: AXIN1 were set to 28808027; 36980886
Phenotypes for gene: AXIN1 were set to craniosynostosis, MONDO:0015469
Review for gene: AXIN1 was set to RED
Added comment: PMID:28808027 reported an individual with sagittal synostosis and a de novo heterozygous variant in AXIN1 gene.
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.106 ARAP3 Achchuthan Shanmugasundram gene: ARAP3 was added
gene: ARAP3 was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: ARAP3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ARAP3 were set to 28808027; 36980886
Phenotypes for gene: ARAP3 were set to craniosynostosis, MONDO:0015469
Review for gene: ARAP3 was set to RED
Added comment: PMID:28808027 reported an individual identified with a de novo variant in ARAP3 (IVS6+1delGT) and presenting with metopic synostosis. As there is only one case reported so far, this gene should be rated red.
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.105 ANKH Achchuthan Shanmugasundram Classified gene: ANKH as Amber List (moderate evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.105 ANKH Achchuthan Shanmugasundram Added comment: Comment on list classification: There are two cases reported in total with craniosynostosis. Hence, this gene can be rated amber.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.105 ANKH Achchuthan Shanmugasundram Gene: ankh has been classified as Amber List (Moderate Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.104 ANKH Achchuthan Shanmugasundram gene: ANKH was added
gene: ANKH was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: ANKH was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ANKH were set to 36118902; 36980886
Phenotypes for gene: ANKH were set to Craniometaphyseal dysplasia, OMIM:123000; craniosynostosis, MONDO:0015469
Review for gene: ANKH was set to AMBER
Added comment: PMID:36118902 reported a single patient with variant in ANKH (c.1129_1132delinsC; p.Phe377del) from a Chinese cohort with syndromic bicoronal and sagittal synostosis. This variant is reported as pathogenic for craniometaphyseal dysplasia in ClinVar and is absent from gnomAD v.2.1.1.

DECIPHER database (https://www.deciphergenomics.org) reported craniosynostosis as one of the clinical presentations in a single patient with heterozygous sequence variant (c.559C​>T; p.Arg187Trp) in ANKH gene. This variant was reported as likely pathogenic.
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.103 ACVRL1 Achchuthan Shanmugasundram changed review comment from: PMID:35997807 reported a cohort of patients with lambdoid synostosis, where a de novo variant (p.Val228Ile) in was identified in ACVRL1. Hence, this gene should be added with a red rating.
Sources: Literature; to: PMID:35997807 reported a cohort of patients with lambdoid synostosis, where a de novo variant (p.Val228Ile) was identified in ACVRL1. Hence, this gene should be added with a red rating.
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.103 ACVR2A Achchuthan Shanmugasundram gene: ACVR2A was added
gene: ACVR2A was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: ACVR2A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ACVR2A were set to 35997807; 36980886
Phenotypes for gene: ACVR2A were set to craniosynostosis, MONDO:0015469
Review for gene: ACVR2A was set to RED
Added comment: PMID:35997807 reported a cohort of patients with lambdoid synostosis, where a de novo variant (p.Thr63Ala) was identified in ACVR2A. Hence, this gene should be added with a red rating.
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.102 ACVRL1 Achchuthan Shanmugasundram Phenotypes for gene: ACVRL1 were changed from to craniosynostosis, MONDO:0015469
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.101 ACVRL1 Achchuthan Shanmugasundram edited their review of gene: ACVRL1: Changed phenotypes to: craniosynostosis, MONDO:0015469
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.101 ACVRL1 Achchuthan Shanmugasundram gene: ACVRL1 was added
gene: ACVRL1 was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature
Mode of inheritance for gene: ACVRL1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ACVRL1 were set to 35997807; 36980886
Review for gene: ACVRL1 was set to RED
Added comment: PMID:35997807 reported a cohort of patients with lambdoid synostosis, where a de novo variant (p.Val228Ile) in was identified in ACVRL1. Hence, this gene should be added with a red rating.
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.100 ABCC9 Achchuthan Shanmugasundram changed review comment from: PMID:24352916 reported a Japanese family with Cantu syndrome, of which the boy had bicoronal synostosis, which was absent in the father. This gene should only be rated red as there is only one case reported so far.; to: PMID:24352916 reported a Japanese family with Cantu syndrome, of which the boy had bicoronal synostosis, which was absent in the father. Craniosynostosis has not previously been reported as part of Cantu syndrome. This gene should only be rated red as there is only one case reported so far.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.100 ABCC9 Achchuthan Shanmugasundram Publications for gene: ABCC9 were set to
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.99 ABCC9 Achchuthan Shanmugasundram Mode of inheritance for gene: ABCC9 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.98 ABCC9 Achchuthan Shanmugasundram reviewed gene: ABCC9: Rating: RED; Mode of pathogenicity: None; Publications: 24352916, 36980886; Phenotypes: Hypertrichotic osteochondrodysplasia (Cantu syndrome), OMIM: 239850; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paroxysmal central nervous system disorders v3.1 ALPK1 Dmitrijs Rots gene: ALPK1 was added
gene: ALPK1 was added to Paroxysmal central nervous system disorders. Sources: Literature
Mode of inheritance for gene: ALPK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ALPK1 were set to PMID: 30967659
Phenotypes for gene: ALPK1 were set to ROSAH syndrome
Mode of pathogenicity for gene: ALPK1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: ALPK1 was set to GREEN
Added comment: ALPK1 is associated with ROSAH syndrome, which commonly include episodic migraine or other headaches.
Sources: Literature
Severe microcephaly v4.28 BUB1 Arina Puzriakova Entity copied from Intellectual disability - microarray and sequencing v5.205
Severe microcephaly v4.28 BUB1 Arina Puzriakova gene: BUB1 was added
gene: BUB1 was added to Severe microcephaly. Sources: Expert Review Amber,Literature
Q4_22_promote_green tags were added to gene: BUB1.
Mode of inheritance for gene: BUB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BUB1 were set to 35044816
Phenotypes for gene: BUB1 were set to Microcephaly 30, primary, autosomal recessive, OMIM:620183
Penetrance for gene: BUB1 were set to Complete
Intellectual disability v5.205 BUB1 Arina Puzriakova Phenotypes for gene: BUB1 were changed from Congenital microcephaly; Global developmental delay; Intellectual disability; Abnormal heart morphology; Growth delay to Microcephaly 30, primary, autosomal recessive, OMIM:620183
Intellectual disability v5.204 BUB1 Arina Puzriakova commented on gene: BUB1
Intellectual disability v5.204 BUB1 Arina Puzriakova Tag Q4_22_MOI was removed from gene: BUB1.
Dilated and arrhythmogenic cardiomyopathy v2.11 TAB2 Arina Puzriakova Entity copied from Paediatric or syndromic cardiomyopathy v3.15
Dilated and arrhythmogenic cardiomyopathy v2.11 TAB2 Arina Puzriakova gene: TAB2 was added
gene: TAB2 was added to Dilated and arrhythmogenic cardiomyopathy. Sources: Expert Review Amber,NHS GMS,London South GLH
Q3_23_promote_green tags were added to gene: TAB2.
Mode of inheritance for gene: TAB2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TAB2 were set to 28464518; 29700987; 32183715; 34456334; 34990405; 34741306; 36000780; 37153890
Phenotypes for gene: TAB2 were set to Congenital heart defects, nonsyndromic, 2, OMIM:614980
Paediatric disorders - additional genes v3.3 TAB2 Arina Puzriakova Entity copied from Paediatric or syndromic cardiomyopathy v3.15
Paediatric disorders - additional genes v3.3 TAB2 Arina Puzriakova gene: TAB2 was added
gene: TAB2 was added to Paediatric disorders - additional genes. Sources: Expert Review Amber,NHS GMS,London South GLH
Q3_23_promote_green tags were added to gene: TAB2.
Mode of inheritance for gene: TAB2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TAB2 were set to 28464518; 29700987; 32183715; 34456334; 34990405; 34741306; 36000780; 37153890
Phenotypes for gene: TAB2 were set to Congenital heart defects, nonsyndromic, 2, OMIM:614980
Paediatric or syndromic cardiomyopathy v3.15 TAB2 Arina Puzriakova Classified gene: TAB2 as Amber List (moderate evidence)
Paediatric or syndromic cardiomyopathy v3.15 TAB2 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update.
Paediatric or syndromic cardiomyopathy v3.15 TAB2 Arina Puzriakova Gene: tab2 has been classified as Amber List (Moderate Evidence).
Paediatric or syndromic cardiomyopathy v3.14 TAB2 Arina Puzriakova Mode of inheritance for gene: TAB2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric or syndromic cardiomyopathy v3.13 TAB2 Arina Puzriakova Publications for gene: TAB2 were set to
Paediatric or syndromic cardiomyopathy v3.12 TAB2 Arina Puzriakova Tag Q3_23_promote_green tag was added to gene: TAB2.
Paediatric or syndromic cardiomyopathy v3.12 TAB2 Arina Puzriakova edited their review of gene: TAB2: Changed publications to: 28464518, 29700987, 32183715, 34456334, 34990405, 34741306, 36000780, 37153890; Changed phenotypes to: Congenital heart defects, nonsyndromic, 2, OMIM:614980
Paediatric or syndromic cardiomyopathy v3.12 TAB2 Arina Puzriakova reviewed gene: TAB2: Rating: GREEN; Mode of pathogenicity: None; Publications: Congenital heart defects, nonsyndromic, 2, OMIM:614980; Phenotypes: 28464518, 29700987, 32183715, 34456334, 34990405, 34741306, 36000780, 37153890; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Infantile nystagmus v1.6 DAGLA Irina Ziravecka gene: DAGLA was added
gene: DAGLA was added to Infantile nystagmus. Sources: Literature
Mode of inheritance for gene: DAGLA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DAGLA were set to PMID: 35737950
Phenotypes for gene: DAGLA were set to developmental delay; ataxia; complex oculomotor abnormality (nystagmus)
Mode of pathogenicity for gene: DAGLA was set to Other
Review for gene: DAGLA was set to GREEN
Added comment: PMID: 35737950 - nine children from eight families with heterozygous, de novo truncating variants in the last exon of DAGLA with a neuro-ocular phenotype.
Sources: Literature
Hereditary ataxia v1.326 DAGLA Irina Ziravecka gene: DAGLA was added
gene: DAGLA was added to Hereditary ataxia. Sources: Literature
Mode of inheritance for gene: DAGLA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DAGLA were set to PMID: 35737950
Phenotypes for gene: DAGLA were set to developmental delay; ataxia; complex oculomotor abnormality
Mode of pathogenicity for gene: DAGLA was set to Other
Review for gene: DAGLA was set to GREEN
Added comment: PMID: 35737950 - nine children from eight families with heterozygous, de novo truncating variants in the last exon of DAGLA with a neuro-ocular phenotype.
Sources: Literature
Intellectual disability v5.204 DAGLA Irina Ziravecka gene: DAGLA was added
gene: DAGLA was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: DAGLA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DAGLA were set to PMID: 35737950
Phenotypes for gene: DAGLA were set to developmental delay; ataxia; complex oculomotor abnormality
Mode of pathogenicity for gene: DAGLA was set to Other
Review for gene: DAGLA was set to GREEN
Added comment: PMID: 35737950 - nine children from eight families with heterozygous, de novo truncating variants in the last exon of DAGLA with a neuro-ocular phenotype.
Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v4.22 MECOM Boaz Palterer gene: MECOM was added
gene: MECOM was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: MECOM was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MECOM were set to 37407873
Phenotypes for gene: MECOM were set to Radioulnar synostosis with amegakaryocytic thrombocytopenia 2, OMIM:616738; Hypocellular bone marrow; congenital thrombocytopenia; B-cell lymphopenia; hypogammaglobulinemia; radioulnar synostosis; digit abnormalities; clubfoot; cardiac defects; facial dysmorphism
Penetrance for gene: MECOM were set to unknown
Review for gene: MECOM was set to GREEN
Added comment: Bone marrow failure syndrome included in the 2022 IUIS IEI classification. A subset of patients presents B cell deficiency and hypogammaglobulinemia. The phenotype is relevant for the panel.
Sources: Literature
Dystonia, chorea or related movement disorder, childhood onset v3.17 TMEM151A Lucy Jackson edited their review of gene: TMEM151A: Changed publications to: 34518509, 35707035, 36724570, 34820915
Dystonia, chorea or related movement disorder, childhood onset v3.17 TMEM151A Lucy Jackson gene: TMEM151A was added
gene: TMEM151A was added to Childhood onset dystonia, chorea or related movement disorder. Sources: NHS GMS
Mode of inheritance for gene: TMEM151A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TMEM151A were set to (PMID: 34518509; 35707035; 36724570; 34820915)
Phenotypes for gene: TMEM151A were set to Episodic kinesigenic dyskinesia 3
Review for gene: TMEM151A was set to GREEN
Added comment: LOF variants have been shown to cause autosomal dominant Episodic kinesigenic dyskinesia 3
Sources: NHS GMS
Neurodegenerative disorders, adult onset v4.28 PPP2R2B_CAG Sarah Leigh Deleted their review
Neurodegenerative disorders, adult onset v4.28 PPP2R2B_CAG Sarah Leigh Tag Q3_23_promote_green was removed from STR: PPP2R2B_CAG.
Neurodegenerative disorders, adult onset v4.28 NOP56_GGCCTG Sarah Leigh Deleted their review
Neurodegenerative disorders, adult onset v4.28 NOP56_GGCCTG Sarah Leigh Tag Q3_23_promote_green was removed from STR: NOP56_GGCCTG.
Neurodegenerative disorders, adult onset v4.28 FXN_GAA Sarah Leigh Deleted their review
Neurodegenerative disorders, adult onset v4.28 FXN_GAA Sarah Leigh Tag Q3_23_promote_green was removed from STR: FXN_GAA.
Neurodegenerative disorders, adult onset v4.28 CSTB_CCCCGCCCCGCG Sarah Leigh Deleted their review
Neurodegenerative disorders, adult onset v4.28 CSTB_CCCCGCCCCGCG Sarah Leigh Tag Q3_23_promote_green was removed from STR: CSTB_CCCCGCCCCGCG.
Neurodegenerative disorders, adult onset v4.28 CACNA1A_CAG Sarah Leigh Deleted their review
Neurodegenerative disorders, adult onset v4.28 CACNA1A_CAG Sarah Leigh Tag Q3_23_promote_green was removed from STR: CACNA1A_CAG.
Neurodegenerative disorders, adult onset v4.28 ATXN7_CAG Sarah Leigh Deleted their review
Neurodegenerative disorders, adult onset v4.28 ATXN7_CAG Sarah Leigh Tag Q3_23_promote_green was removed from STR: ATXN7_CAG.
Neurodegenerative disorders, adult onset v4.28 ATXN3_CAG Sarah Leigh Deleted their review
Neurodegenerative disorders, adult onset v4.28 ATXN3_CAG Sarah Leigh Tag Q3_23_promote_green was removed from STR: ATXN3_CAG.
Neurodegenerative disorders, adult onset v4.28 ATXN2_CAG Sarah Leigh Deleted their review
Neurodegenerative disorders, adult onset v4.28 ATXN2_CAG Sarah Leigh Tag Q3_23_promote_green was removed from STR: ATXN2_CAG.
Neurodegenerative disorders, adult onset v4.28 ATXN10_ATTCT Sarah Leigh Deleted their review
Neurodegenerative disorders, adult onset v4.28 ATXN1_CAG Sarah Leigh Deleted their review
Neurodegenerative disorders, adult onset v4.28 ATXN1_CAG Sarah Leigh Deleted their comment
Neurodegenerative disorders, adult onset v4.28 ATXN1_CAG Sarah Leigh Tag Q3_23_promote_green was removed from STR: ATXN1_CAG.
Neurodegenerative disorders, adult onset v4.28 ATXN10_ATTCT Sarah Leigh Deleted their comment
Neurodegenerative disorders, adult onset v4.28 ATXN10_ATTCT Sarah Leigh Tag Q3_23_promote_green was removed from STR: ATXN10_ATTCT.
Mitochondrial disorders v4.56 SLC22A5 Sarah Leigh changed review comment from: Numerous SLC22A5 variants are associated with a relevant phenotype in OMIM (OMIM:212140) and SLC22A5 has a definitive association in Gen2Phen for Systemic Carnitine Deficiency. A supportive mouse model has also been reported (PMID: 17884651).; to: Numerous SLC22A5 variants have been associated with OMIM:212140, and SLC22A5 has a definitive association in Gen2Phen for Systemic Carnitine Deficiency. A supportive mouse model has also been reported (PMID: 17884651).
Mitochondrial disorders v4.56 SLC22A5 Sarah Leigh edited their review of gene: SLC22A5: Added comment: Numerous SLC22A5 variants are associated with a relevant phenotype in OMIM (OMIM:212140) and SLC22A5 has a definitive association in Gen2Phen for Systemic Carnitine Deficiency. A supportive mouse model has also been reported (PMID: 17884651).; Changed rating: GREEN
Mitochondrial disorders v4.56 SLC22A5 Sarah Leigh Publications for gene: SLC22A5 were set to 9916797; 17884651; 25778941
Mitochondrial disorders v4.55 SLC22A5 Sarah Leigh Tag Q3_23_promote_green tag was added to gene: SLC22A5.
Mitochondrial disorders v4.55 SLC22A5 Sarah Leigh Classified gene: SLC22A5 as Amber List (moderate evidence)
Mitochondrial disorders v4.55 SLC22A5 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Mitochondrial disorders v4.55 SLC22A5 Sarah Leigh Gene: slc22a5 has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v4.54 SLC22A5 Sarah Leigh Publications for gene: SLC22A5 were set to 9916797; 25778941; 17884651; 25778941
Mitochondrial disorders v4.53 SLC22A5 Sarah Leigh Phenotypes for gene: SLC22A5 were changed from Carnitine deficiency, systemic primary, 212140 to Carnitine deficiency, systemic primary, OMIM:212140; systemic primary carnitine deficiency disease, MONDO:0008919
Mitochondrial disorders v4.52 SLC22A5 Sarah Leigh Publications for gene: SLC22A5 were set to
RASopathies v1.78 MAP4K4 Irina Ziravecka gene: MAP4K4 was added
gene: MAP4K4 was added to RASopathies. Sources: Literature
Mode of inheritance for gene: MAP4K4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAP4K4 were set to PMID: 37126546
Phenotypes for gene: MAP4K4 were set to neurodevelopmental differences; multiple congenital anomalies
Mode of pathogenicity for gene: MAP4K4 was set to Other
Review for gene: MAP4K4 was set to GREEN
Added comment: PMID: 37126546 - "a cohort of 26 affected individuals from 21 unrelated families with neurodevelopmental differences, cardiac issues, and CFAs who share a phenotype overlap with RASopathies and harbor a series of rare variants in MAP4K4.
Functional studies in zebrafish showed that MAP4K4 variants caused hypomorphic, LOF, or DN effects."
Sources: Literature
DDG2P v3.6 MAP4K4 Irina Ziravecka gene: MAP4K4 was added
gene: MAP4K4 was added to DDG2P. Sources: Literature
Mode of inheritance for gene: MAP4K4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAP4K4 were set to PMID: 37126546
Phenotypes for gene: MAP4K4 were set to neurodevelopmental differences; multiple congenital anomalies
Mode of pathogenicity for gene: MAP4K4 was set to Other
Review for gene: MAP4K4 was set to GREEN
Added comment: PMID: 37126546 - "a cohort of 26 affected individuals from 21 unrelated families with neurodevelopmental differences, cardiac issues, and CFAs who share a phenotype overlap with RASopathies and harbor a series of rare variants in MAP4K4.
Functional studies in zebrafish showed that MAP4K4 variants caused hypomorphic, LOF, or DN effects."
Sources: Literature
DDG2P v3.6 AMOTL1 Irina Ziravecka edited their review of gene: AMOTL1: Added comment: PMID: 36751037 - this cohort suggests that heterozygous missense variants in AMOTL1, most commonly affecting amino acid residues 157–161, define a new orofacial clefting syndrome, and indicates an important functional role for this undefined region.
5 out of 16 patients in this cohort have developmental delay.; Changed phenotypes to: orofacial clefting, cardiac anomalies, tall stature, distinct dysmorphisms (abnormal head shape, craniosynostosis, hypertelorism, and large ears), myopia, hearing loss, micrognathia, immune dysfunction, scoliosis, chronic constipation, liver dysfunction, global developmental delay
DDG2P v3.6 AMOTL1 Irina Ziravecka Deleted their comment
DDG2P v3.6 AMOTL1 Irina Ziravecka changed review comment from: PMID: 36751037 - this cohort suggests that heterozygous missense variants in AMOTL1, most commonly affecting amino acid residues 157–161, define a new orofacial clefting syndrome, and indicates an important functional role for this undefined region.
Sources: Other; to: PMID: 36751037 - this cohort suggests that heterozygous missense variants in AMOTL1, most commonly affecting amino acid residues 157–161, define a new orofacial clefting syndrome, and indicates an important functional role for this undefined region.
5 out of 16 patients in this cohort have developmental delay.
DDG2P v3.6 AMOTL1 Irina Ziravecka gene: AMOTL1 was added
gene: AMOTL1 was added to DDG2P. Sources: Other
Mode of inheritance for gene: AMOTL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AMOTL1 were set to PMID: 36751037
Phenotypes for gene: AMOTL1 were set to orofacial clefting; cardiac anomalies; tall stature
Mode of pathogenicity for gene: AMOTL1 was set to Other
Review for gene: AMOTL1 was set to GREEN
Added comment: PMID: 36751037 - this cohort suggests that heterozygous missense variants in AMOTL1, most commonly affecting amino acid residues 157–161, define a new orofacial clefting syndrome, and indicates an important functional role for this undefined region.
Sources: Other
Clefting v4.78 AMOTL1 Irina Ziravecka reviewed gene: AMOTL1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 36751037; Phenotypes: orofacial clefting, cardiac anomalies, tall stature; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v4.10 SETD5 Tracy Lester gene: SETD5 was added
gene: SETD5 was added to Skeletal dysplasia. Sources: NHS GMS
Mode of inheritance for gene: SETD5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SETD5 were set to 28881385
Phenotypes for gene: SETD5 were set to Skeletal dysplasia; intellectual disability; developmental delay; facial dysmorphism
Penetrance for gene: SETD5 were set to Incomplete
Review for gene: SETD5 was set to GREEN
Added comment: This gene is associated with an autosomal dominant neurodevelopmental disorder characterised by developmental delay, intellectual disability, and variable dysmorphic and skeletal abnormalities. Expressivity is variable and non-penetrance has been reported. As the skeletal features might appear before the ID/DD I think this gene should be added to the SD panel. We recently found a pathogenic fs in this gene in a child with short stature, short long bones and facial dysmorphism but without mention of DD/ID; however case was only 10m old at referral.
Sources: NHS GMS
Hereditary ataxia, adult onset v4.15 PRPS1 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: All female cases from the three families were reported with X-linked dominant variants in PRPS1 gene. Hence, the MOI should be changed to "X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)".
Hereditary ataxia, adult onset v4.15 PRPS1 Achchuthan Shanmugasundram Mode of inheritance for gene: PRPS1 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Hereditary ataxia, adult onset v4.14 PRPS1 Achchuthan Shanmugasundram Phenotypes for gene: PRPS1 were changed from Ataxia; deafness; eye disease to cerebellar ataxia, MONDO:0000437
Hereditary ataxia, adult onset v4.13 PRPS1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: Three families reported with adult-onset ataxia. Although ataxia has been reported in the proband and her mother with X-linked dominant variant in a family in PMID:28967191, it was not reported in the older sister from the family with the same variant. Due to the reduced penetrance in this family, this gene should only be rated amber.; to: Comment on list classification: As reviewed by Zornitza Stark, three families were reported with adult-onset ataxia. Although ataxia has been reported in the proband and her mother with X-linked dominant variant in a family in PMID:28967191, it was not reported in the older sister from the family with the same variant. Due to the reduced penetrance in this family, this gene should only be rated amber.
Hereditary ataxia, adult onset v4.13 PRPS1 Achchuthan Shanmugasundram Classified gene: PRPS1 as Amber List (moderate evidence)
Hereditary ataxia, adult onset v4.13 PRPS1 Achchuthan Shanmugasundram Added comment: Comment on list classification: Three families reported with adult-onset ataxia. Although ataxia has been reported in the proband and her mother with X-linked dominant variant in a family in PMID:28967191, it was not reported in the older sister from the family with the same variant. Due to the reduced penetrance in this family, this gene should only be rated amber.
Hereditary ataxia, adult onset v4.13 PRPS1 Achchuthan Shanmugasundram Gene: prps1 has been classified as Amber List (Moderate Evidence).
Hereditary ataxia, adult onset v4.12 PRPS1 Achchuthan Shanmugasundram reviewed gene: PRPS1: Rating: AMBER; Mode of pathogenicity: None; Publications: 25491489, 28967191, 33898739; Phenotypes: cerebellar ataxia, MONDO:0000437; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v5.204 PTPA Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.204 PTPA Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.204 PTPA Achchuthan Shanmugasundram Classified gene: PTPA as Amber List (moderate evidence)
Intellectual disability v5.204 PTPA Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Konstantinos Varvagiannis, there are two unrelated cases with intellectual disability and hence this gene should be rated amber.
Intellectual disability v5.204 PTPA Achchuthan Shanmugasundram Gene: ptpa has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.203 PTPA Achchuthan Shanmugasundram Classified gene: PTPA as Amber List (moderate evidence)
Intellectual disability v5.203 PTPA Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Konstantinos Varvagiannis, there are two unrelated cases with intellectual disability and hence this gene should be rated amber.
Intellectual disability v5.203 PTPA Achchuthan Shanmugasundram Gene: ptpa has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.203 PTPA Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.203 PTPA Achchuthan Shanmugasundram Classified gene: PTPA as Amber List (moderate evidence)
Intellectual disability v5.203 PTPA Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Konstantinos Varvagiannis, there are two unrelated cases with intellectual disability and hence this gene should be rated amber.
Intellectual disability v5.203 PTPA Achchuthan Shanmugasundram Gene: ptpa has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.203 PTPA Achchuthan Shanmugasundram Classified gene: PTPA as Amber List (moderate evidence)
Intellectual disability v5.203 PTPA Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Konstantinos Varvagiannis, there are two unrelated cases with intellectual disability and hence this gene should be rated amber.
Intellectual disability v5.203 PTPA Achchuthan Shanmugasundram Gene: ptpa has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.202 PTPA Achchuthan Shanmugasundram Phenotypes for gene: PTPA were changed from Intellectual disability, MONDO:0001071 to Intellectual disability, MONDO:0001071
Intellectual disability v5.202 PTPA Achchuthan Shanmugasundram Phenotypes for gene: PTPA were changed from Intellectual disability, MONDO:0001071 to Intellectual disability, MONDO:0001071
Intellectual disability v5.201 PTPA Achchuthan Shanmugasundram Phenotypes for gene: PTPA were changed from Intellectual disability, MONDO:0001071 to Intellectual disability, MONDO:0001071
Intellectual disability v5.201 PTPA Achchuthan Shanmugasundram Phenotypes for gene: PTPA were changed from Intellectual disability, MONDO:0001071 to Intellectual disability, MONDO:0001071
Intellectual disability v5.201 PTPA Achchuthan Shanmugasundram Phenotypes for gene: PTPA were changed from Intellectual disability; Parkinsonism to Intellectual disability, MONDO:0001071
Intellectual disability v5.200 PTPA Achchuthan Shanmugasundram reviewed gene: PTPA: Rating: AMBER; Mode of pathogenicity: None; Publications: 36073231; Phenotypes: Intellectual disability, MONDO:0001071; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram Classified gene: FOXR1 as Amber List (moderate evidence)
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there is one case with global developmental delay and supporting functional evidence including mouse model. Hence, this gene should be rated amber.
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram Gene: foxr1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Zornitza Stark, there is one case with global developmental delay and supporting functional evidence including mouse model. Hence, this gene should be rated amber.; to: Comment on list classification: As reviewed by Zornitza Stark, there is one case with global developmental delay supported by functional evidence including mouse model. Hence, this gene should be rated amber.
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram Classified gene: FOXR1 as Amber List (moderate evidence)
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there is one case with global developmental delay and supporting functional evidence including mouse model. Hence, this gene should be rated amber.
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram Gene: foxr1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Classified gene: FOXR1 as Amber List (moderate evidence)
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there is one case with global developmental delay and supporting functional evidence including mouse model. Hence, this gene should be rated amber.
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Gene: foxr1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram Classified gene: FOXR1 as Amber List (moderate evidence)
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there is one case with global developmental delay and supporting functional evidence including mouse model. Hence, this gene should be rated amber.
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram Gene: foxr1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Classified gene: FOXR1 as Amber List (moderate evidence)
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there is one case with global developmental delay and supporting functional evidence including mouse model. Hence, this gene should be rated amber.
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Gene: foxr1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Classified gene: FOXR1 as Amber List (moderate evidence)
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there is one case with global developmental delay and supporting functional evidence including mouse model. Hence, this gene should be rated amber.
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Gene: foxr1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Classified gene: FOXR1 as Amber List (moderate evidence)
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there is one case with global developmental delay and supporting functional evidence including mouse model. Hence, this gene should be rated amber.
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Gene: foxr1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Classified gene: FOXR1 as Amber List (moderate evidence)
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there is one case with global developmental delay and supporting functional evidence including mouse model. Hence, this gene should be rated amber.
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Gene: foxr1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.198 FOXR1 Achchuthan Shanmugasundram Phenotypes for gene: FOXR1 were changed from Global developmental delay, HP:0001263; microcephaly, MONDO:0001149; Brain atrophy, HP:0012444 to Global developmental delay, HP:0001263; microcephaly, MONDO:0001149; Brain atrophy, HP:0012444
Intellectual disability v5.198 FOXR1 Achchuthan Shanmugasundram Phenotypes for gene: FOXR1 were changed from Global developmental delay, HP:0001263; microcephaly, MONDO:0001149; Brain atrophy, HP:0012444 to Global developmental delay, HP:0001263; microcephaly, MONDO:0001149; Brain atrophy, HP:0012444
Intellectual disability v5.198 FOXR1 Achchuthan Shanmugasundram Phenotypes for gene: FOXR1 were changed from Global developmental delay, HP:0001263; microcephaly, MONDO:0001149; Brain atrophy, HP:0012444 to Global developmental delay, HP:0001263; microcephaly, MONDO:0001149; Brain atrophy, HP:0012444
Intellectual disability v5.198 FOXR1 Achchuthan Shanmugasundram Phenotypes for gene: FOXR1 were changed from Global developmental delay, HP:0001263; microcephaly, MONDO:0001149; Brain atrophy, HP:0012444 to Global developmental delay, HP:0001263; microcephaly, MONDO:0001149; Brain atrophy, HP:0012444
Intellectual disability v5.197 FOXR1 Achchuthan Shanmugasundram Phenotypes for gene: FOXR1 were changed from Global developmental delay, HP:0001263; microcephaly, MONDO:0001149; Brain atrophy, HP:0012444 to Global developmental delay, HP:0001263; microcephaly, MONDO:0001149; Brain atrophy, HP:0012444
Intellectual disability v5.197 FOXR1 Achchuthan Shanmugasundram Phenotypes for gene: FOXR1 were changed from Postnatal microcephaly, progressive brain atrophy and global developmental delay to Global developmental delay, HP:0001263; microcephaly, MONDO:0001149; Brain atrophy, HP:0012444
Intellectual disability v5.196 FOXR1 Achchuthan Shanmugasundram edited their review of gene: FOXR1: Changed phenotypes to: Global developmental delay, HP:0001263, microcephaly, MONDO:0001149, Brain atrophy, HP:0012444
Intellectual disability v5.196 FOXR1 Achchuthan Shanmugasundram reviewed gene: FOXR1: Rating: AMBER; Mode of pathogenicity: None; Publications: 34723967; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal tubulopathies v4.1 RMND1 John Sayer gene: RMND1 was added
gene: RMND1 was added to Renal tubulopathies. Sources: Expert list
Mode of inheritance for gene: RMND1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RMND1 were set to 32911714; 31889854; 31568715
Phenotypes for gene: RMND1 were set to tubulopathy; renal tubular acidosis; interstitial nephritis; end-stage renal disease; tubular atrophy
Penetrance for gene: RMND1 were set to Complete
Mode of pathogenicity for gene: RMND1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: RMND1 was set to GREEN
Added comment: Sources: Expert list
Intellectual disability v5.196 KDM6B Sarah Leigh Phenotypes for gene: KDM6B were changed from Neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities, 618505 to Neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities, OMIM:618505; neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities, MONDO:0032790
Early onset or syndromic epilepsy v4.67 KDM6B Sarah Leigh edited their review of gene: KDM6B: Added comment: KDM6B variants have been associated with relevant phenotype in OMIM and as strong Gen2Phen gene for KDM6B-related developmental disorder (monoallelic). PMID: 37196654 reports that in their cohort, 9/69 (13%) of individuals had seizures.; Changed rating: GREEN
Early onset or syndromic epilepsy v4.67 KDM6B Sarah Leigh Classified gene: KDM6B as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.67 KDM6B Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Early onset or syndromic epilepsy v4.67 KDM6B Sarah Leigh Gene: kdm6b has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.66 KDM6B Sarah Leigh Tag Q3_23_promote_green tag was added to gene: KDM6B.
Early onset or syndromic epilepsy v4.66 KDM6B Sarah Leigh Phenotypes for gene: KDM6B were changed from Global developmental delay; Intellectual disability; Hypotonia; Joint hypermobility; seizures; Overgrowth to Neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities, OMIM:618505; neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities, MONDO:0032790
Early onset or syndromic epilepsy v4.65 KDM6B Sarah Leigh Publications for gene: KDM6B were set to PMID: 37196654
Intellectual disability v5.195 KDM6B Sarah Leigh Publications for gene: KDM6B were set to 21937992; 31124279
Early onset or syndromic epilepsy v4.64 DALRD3 Arina Puzriakova Classified gene: DALRD3 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.64 DALRD3 Arina Puzriakova Added comment: Comment on list classification: New gene added by Konstantinos Varvagiannis. Rating Amber as this is a good candidate gene but only a single family has been reported to date with variants. Additional evidence needed prior to adding the gene as diagnostic-grade.
Early onset or syndromic epilepsy v4.64 DALRD3 Arina Puzriakova Gene: dalrd3 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.63 DALRD3 Arina Puzriakova Classified gene: DALRD3 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.63 DALRD3 Arina Puzriakova Added comment: Comment on list classification: New gene added by Konstantinos Varvagiannis. Rating Amber as this is a good candidate gene but only a single family has been reported to date with variants. Additional evidence needed prior to adding the gene as diagnostic-grade.
Early onset or syndromic epilepsy v4.63 DALRD3 Arina Puzriakova Gene: dalrd3 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.194 DALRD3 Arina Puzriakova Classified gene: DALRD3 as Amber List (moderate evidence)
Intellectual disability v5.194 DALRD3 Arina Puzriakova Added comment: Comment on list classification: New gene added by Konstantinos Varvagiannis. Rating Amber as this is a good candidate gene but only a single family has been reported to date with variants. Additional evidence needed prior to adding the gene as diagnostic-grade.
Intellectual disability v5.194 DALRD3 Arina Puzriakova Gene: dalrd3 has been classified as Amber List (Moderate Evidence).
Familial breast cancer v1.20 ATRIP Arina Puzriakova Mode of inheritance for gene: ATRIP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Familial breast cancer v1.19 ATRIP Arina Puzriakova Classified gene: ATRIP as Amber List (moderate evidence)
Familial breast cancer v1.19 ATRIP Arina Puzriakova Added comment: Comment on list classification: New gene added to this panel by Lauma Freimane. More evidence is required prior to adding this gene to the panel. The metanalysis paper identified by reviewer is still at the preprint stage. The findings are detailed below but this needs to be revisited once the article has been published. This is a good candidate gene for breast cancer susceptibility but for now can only classify as Amber (with watchlist tag), awaiting peer-review and additional publication of supporting evidence.
Familial breast cancer v1.19 ATRIP Arina Puzriakova Gene: atrip has been classified as Amber List (Moderate Evidence).
Familial breast cancer v1.18 ATRIP Arina Puzriakova commented on gene: ATRIP
Breast cancer pertinent cancer susceptibility v2.2 ATRIP Arina Puzriakova changed review comment from: Enrichment for ATRIP variants was found in meta-analysis of breast cancer cohorts and UK Biobank. ATRIP carriers had a higher proportion of high-grade, low-stage ductal breast cancer but none of the associations with tumor characteristics were statistically significant.

Another study (PMID: 36977412) also identified three Polish women with familial breast cancer and variants in this gene including a c.69_75dup (p.Thr26Alafs∗23) frameshift insertion (not discussed further in paper) and a founder c.1152_1155del (p.Gly385Ter) frameshift deletion in two women. The founder variant was also found in validation cohorts with 42/16,085 unselected Polish breast cancer-affected individuals and 11/9,285 control subjects (OR = 2.14, 95% CI = 1.13-4.28, p = 0.02) harbouring the variant. UK Biobank data showed ATRIP loss-of-function variants among 13/15,643 breast cancer-affected individuals versus 40/157,943 control subjects (OR = 3.28, 95% CI = 1.76-6.14, p < 0.001).

Immunohistochemistry and functional studies showed the ATRIP c.1152_1155del variant allele is weakly expressed compared to the wild-type allele, and truncated ATRIP fails to perform its normal function to prevent replicative stress.
-----

ATRIP is currently not associated with any phenotype in OMIM or G2P. It codes for a DNA damage response protein which forms a complex with ATR. ATR-ATRIP is involved in the process that activates checkpoint signalling when single-stranded DNA is detected following the processing of DNA double-stranded breaks or stalled replication forks.; to: Enrichment for ATRIP variants was found in meta-analysis of breast cancer cohorts and UK Biobank. ATRIP carriers had a higher proportion of high-grade, low-stage ductal breast cancer but none of the associations with tumor characteristics were statistically significant (https://doi.org/10.1101/2022.06.17.22276537).

Another study (PMID: 36977412) also identified three Polish women with familial breast cancer and variants in this gene including a c.69_75dup (p.Thr26Alafs∗23) frameshift insertion (not discussed further in paper) and a founder c.1152_1155del (p.Gly385Ter) frameshift deletion in two women. The founder variant was also found in validation cohorts with 42/16,085 unselected Polish breast cancer-affected individuals and 11/9,285 control subjects (OR = 2.14, 95% CI = 1.13-4.28, p = 0.02) harbouring the variant. UK Biobank data showed ATRIP loss-of-function variants among 13/15,643 breast cancer-affected individuals versus 40/157,943 control subjects (OR = 3.28, 95% CI = 1.76-6.14, p < 0.001).

Immunohistochemistry and functional studies showed the ATRIP c.1152_1155del variant allele is weakly expressed compared to the wild-type allele, and truncated ATRIP fails to perform its normal function to prevent replicative stress.
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ATRIP is currently not associated with any phenotype in OMIM or G2P. It codes for a DNA damage response protein which forms a complex with ATR. ATR-ATRIP is involved in the process that activates checkpoint signalling when single-stranded DNA is detected following the processing of DNA double-stranded breaks or stalled replication forks.
Breast cancer pertinent cancer susceptibility v2.2 ATRIP Arina Puzriakova Classified gene: ATRIP as Amber List (moderate evidence)
Breast cancer pertinent cancer susceptibility v2.2 ATRIP Arina Puzriakova Added comment: Comment on list classification: New gene added to this panel by Lauma Freimane. More evidence is required prior to adding this gene to the panel. The metanalysis paper identified by reviewer is still at the preprint stage. The findings are detailed below but this needs to be revisited once the article has been published. This is a good candidate gene for breast cancer susceptibility but for now can only classify as Amber (with watchlist tag), awaiting peer-review and additional publication of supporting evidence.
Breast cancer pertinent cancer susceptibility v2.2 ATRIP Arina Puzriakova Gene: atrip has been classified as Amber List (Moderate Evidence).
Breast cancer pertinent cancer susceptibility v2.1 ATRIP Arina Puzriakova Tag watchlist tag was added to gene: ATRIP.
Breast cancer pertinent cancer susceptibility v2.1 ATRIP Arina Puzriakova commented on gene: ATRIP
Intellectual disability v5.193 SMCHD1 Arina Puzriakova Mode of inheritance for gene: SMCHD1 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Facioscapulohumeral muscular dystrophy - extended testing v0.1 SMCHD1 Arina Puzriakova Tag digenic tag was added to gene: SMCHD1.
Inherited polyposis and early onset colorectal cancer - germline testing v2.6 GREM1 Arina Puzriakova Mode of pathogenicity for gene: GREM1 was changed from to Other
Adult solid tumours for rare disease v1.36 PDGFRA Sumir Pandit reviewed gene: PDGFRA: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 29486293; Phenotypes: ; Mode of inheritance: None
Inherited polyposis and early onset colorectal cancer - germline testing v2.5 GREM1 Arina Puzriakova Added comment: Comment on phenotypes: Previous phenotypes:
Hereditary Mixed Polyposis Syndrome;Oligosyndactyly of the hands, Cenani-Linz-like (Dimitrov (2010) J Med Genet 47,569);Polyposis Syndrome, Hereditary Mixed, 1;Mixed polyposis syndrome (Jaeger (2012) Nat Genet 44,699);{Colorectal cancer, increased risk, association with}(Peters (2012) Hum Genet 131,217)
Inherited polyposis and early onset colorectal cancer - germline testing v2.5 GREM1 Arina Puzriakova Phenotypes for gene: GREM1 were changed from Hereditary Mixed Polyposis Syndrome; Oligosyndactyly of the hands, Cenani-Linz-like (Dimitrov (2010) J Med Genet 47,569); Polyposis Syndrome, Hereditary Mixed, 1; Mixed polyposis syndrome (Jaeger (2012) Nat Genet 44,699); {Colorectal cancer, increased risk, association with}(Peters (2012) Hum Genet 131,217) to Hereditary mixed polyposis syndrome, MONDO:0011023
Paediatric or syndromic cardiomyopathy v3.12 ELAC2 Matthew Edwards gene: ELAC2 was added
gene: ELAC2 was added to Paediatric or syndromic cardiomyopathy. Sources: Expert Review
Mode of inheritance for gene: ELAC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ELAC2 were set to PMID: 23849775
Penetrance for gene: ELAC2 were set to unknown
Review for gene: ELAC2 was set to GREEN
Added comment: Oxidative phosphorylation deficiency-17 manifests as severe infantile-onset hypertrophic cardiomyopathy (green gene on several metabolic panels, but presenting feature is HCM in first year of life)

Also recent diagnostic case through our GLH
Sources: Expert Review
Retinal disorders v4.12 MCOLN1 Siying Lin gene: MCOLN1 was added
gene: MCOLN1 was added to Retinal disorders. Sources: Literature
Mode of inheritance for gene: MCOLN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCOLN1 were set to 17239335; 1488220; 18326692
Mode of pathogenicity for gene: MCOLN1 was set to Other
Review for gene: MCOLN1 was set to GREEN
Added comment: Retinal degeneration is a known feature of MCOLN1-associated mucolipidosis IV, and there are reports of patients presenting with a limited ocular phenotype including retinal dystrophy
Sources: Literature
Hereditary ataxia v1.326 DMXL2 Arina Puzriakova Mode of inheritance for gene: DMXL2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - childhood onset v4.17 DMXL2 Arina Puzriakova Mode of inheritance for gene: DMXL2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - childhood onset v4.16 DMXL2 Arina Puzriakova Classified gene: DMXL2 as Red List (low evidence)
Ataxia and cerebellar anomalies - childhood onset v4.16 DMXL2 Arina Puzriakova Added comment: Comment on list classification: Downgraded from Amber to Red. Ataxia (onset in adolescence) has only been reported in one consanguineous family to date (PMID: 25248098) and this finding has not since been replicated. Therefore demoting the gene rating, inline with review by Dmitrijs Rots.
Ataxia and cerebellar anomalies - childhood onset v4.16 DMXL2 Arina Puzriakova Gene: dmxl2 has been classified as Red List (Low Evidence).
Hereditary ataxia v1.325 DMXL2 Arina Puzriakova Publications for gene: DMXL2 were set to 27657680; 22875945; 25248098
Ataxia and cerebellar anomalies - childhood onset v4.15 DMXL2 Arina Puzriakova Publications for gene: DMXL2 were set to 25248098; 22875945; 27657680
Hereditary ataxia v1.324 DMXL2 Arina Puzriakova Phenotypes for gene: DMXL2 were changed from ?Polyendocrine-polyneuropathy syndrome , OMIM:616113 to ?Polyendocrine-polyneuropathy syndrome, OMIM:616113
Ataxia and cerebellar anomalies - childhood onset v4.14 DMXL2 Arina Puzriakova Phenotypes for gene: DMXL2 were changed from Sensorineural Hearing Loss; ORPHA90636; OMIM:612186 to ?Polyendocrine-polyneuropathy syndrome, OMIM:616113
Hereditary ataxia v1.323 DMXL2 Arina Puzriakova Phenotypes for gene: DMXL2 were changed from Sensorineural Hearing Loss; ORPHA90636; OMIM:612186 to ?Polyendocrine-polyneuropathy syndrome , OMIM:616113
Hereditary ataxia v1.322 DMXL2 Arina Puzriakova Classified gene: DMXL2 as Red List (low evidence)
Hereditary ataxia v1.322 DMXL2 Arina Puzriakova Added comment: Comment on list classification: Downgraded from Amber to Red. Ataxia (onset in adolescence) has only been reported in one consanguineous family to date (PMID: 25248098) and this finding has not since been replicated. Therefore demoting the gene rating, inline with review by Dmitrijs Rots.
Hereditary ataxia v1.322 DMXL2 Arina Puzriakova Gene: dmxl2 has been classified as Red List (Low Evidence).
Early onset or syndromic epilepsy v4.62 CPA6 John Taylor changed review comment from: The pathology of this gene is predicated on two publications: Salzmann et al. (2012) PubMed: 21922598 and Sapio et al. (2012) PubMed: 23105115. Both of these publications were issued prior to large population-based allele assessments and the evidence for pathogenicity is reliant on circumstantial evidence. None of the variants that form the foundation of this disease link would have sufficient evidence in support pathogenicity using current classification criteria. This gene should be recategorized as having a Red rating.

Evidence against pathogenicity for the reported variants:
Salzmann et al. (2012) proposed haploinsufficiency rather than gain of function; however, there is no obvious constraint score across the length of the gene. Previously reported pathogenic variants are, in some cases (see below), present in gnomAD at allele frequencies contrary to the incidence of the associated condition.

CPA6 p.(Ala270Val) rs114402678 has been reported has a homozygous variant in gnomADv3.1.2 in the non-neuro sub category (only samples that were not collected as part of a neurologic or psychiatric case/control study, or samples collected as part of a neurologic or psychiatric case/control study but designated as controls). The allele frequency and the observed number of homozygotes is not significantly different from the number of expected homozygote alleles based on the Hardy-Weinberg equilibrium.

CPA6(NM_020361.5):c.799G>A p.(Gly267Arg) rs61738009 was reported as a heterozygous pathogenic variant; however, this variant has been reported in >860 heterozygous individuals in gnomADv2.1.1 and v3.1.2.; to: The pathology of this gene is predicated on two publications: Salzmann et al. (2012) PubMed: 21922598 and Sapio et al. (2012) PubMed: 23105115. Both of these publications were issued prior to large population-based allele assessments and the evidence for pathogenicity is reliant on circumstantial evidence. None of the variants that form the foundation of this disease link would have sufficient evidence in support pathogenicity using current classification criteria. This gene should be recategorized as having a Red rating.

Evidence against pathogenicity for the reported variants:
Salzmann et al. (2012) proposed haploinsufficiency rather than gain of function; however, there is no obvious constraint score across the length of the gene. Previously reported pathogenic variants are, in some cases (see below), present in gnomAD at allele frequencies contrary to the incidence of the associated condition.

CPA6 p.(Ala270Val) rs114402678 has been reported has a homozygous variant in gnomADv3.1.2 in the non-neuro sub category (only samples that were not collected as part of a neurologic or psychiatric case/control study, or samples collected as part of a neurologic or psychiatric case/control study but designated as controls). The allele frequency and the observed number of homozygotes is not significantly different from the number of expected homozygote alleles based on the Hardy-Weinberg equilibrium.

CPA6(NM_020361.5):c.799G>A p.(Gly267Arg) rs61738009 was reported as a heterozygous pathogenic variant; however, this variant has been reported in >860 heterozygous individuals in gnomADv2.1.1 and v3.1.2.
Early onset or syndromic epilepsy v4.62 CPA6 John Taylor reviewed gene: CPA6: Rating: RED; Mode of pathogenicity: Other; Publications: PMID:21922598, 23105115; Phenotypes: ; Mode of inheritance: Other
Wiskott-Aldrich syndrome v0.1 WAS Achchuthan Shanmugasundram reviewed gene: WAS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Wilson disease v0.1 ATP7B Achchuthan Shanmugasundram reviewed gene: ATP7B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
von Willebrand disease v0.1 VWF Achchuthan Shanmugasundram reviewed gene: VWF: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Von Hippel Lindau syndrome v0.1 VHL Achchuthan Shanmugasundram reviewed gene: VHL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Variegate porphyria v0.1 PPOX Achchuthan Shanmugasundram reviewed gene: PPOX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Tuberous sclerosis v0.1 TSC2 Achchuthan Shanmugasundram reviewed gene: TSC2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Tuberous sclerosis v0.1 TSC1 Achchuthan Shanmugasundram reviewed gene: TSC1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Thiamine metabolism dysfunction syndrome 2 v0.1 SLC19A3 Achchuthan Shanmugasundram reviewed gene: SLC19A3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Thanatophoric dysplasia v0.1 FGFR3 Achchuthan Shanmugasundram reviewed gene: FGFR3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sickle cell, thalassaemia and other haemoglobinopathies v0.1 HBB Achchuthan Shanmugasundram reviewed gene: HBB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sickle cell, thalassaemia and other haemoglobinopathies v0.1 HBA1 Achchuthan Shanmugasundram reviewed gene: HBA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Tay-Sachs disease v0.1 HEXA Achchuthan Shanmugasundram reviewed gene: HEXA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Syndromic and non syndromic craniosynostosis involving midline sutures v0.1 SMAD6 Achchuthan Shanmugasundram changed review comment from: SMAD6 has been added to the panel for R416 Syndromic and non syndromic craniosynostosis involving midline sutures only with a green rating as agreed with the NHS Genomic Medicine Service.; to: SMAD6 has been added to the panel for R416 Syndromic and non syndromic craniosynostosis involving midline sutures with a green rating as agreed with the NHS Genomic Medicine Service.
Syndromic and non syndromic craniosynostosis involving midline sutures v0.1 SMAD6 Achchuthan Shanmugasundram reviewed gene: SMAD6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Subcutaneous panniculitis T-cell lymphoma (SPTCL) v0.1 HAVCR2 Achchuthan Shanmugasundram reviewed gene: HAVCR2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Spinal muscular atrophy - Diagnostic v0.1 SMN1 Achchuthan Shanmugasundram reviewed gene: SMN1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Smith-Lemli-Opitz syndrome v0.1 DHCR7 Achchuthan Shanmugasundram reviewed gene: DHCR7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Sitosterolaemia v0.1 ABCG8 Achchuthan Shanmugasundram reviewed gene: ABCG8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Sitosterolaemia v0.1 ABCG5 Achchuthan Shanmugasundram reviewed gene: ABCG5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Short stature - SHOX deficiency v0.1 SHOX Achchuthan Shanmugasundram reviewed gene: SHOX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Severe combined immunodeficiency with PNP deficiency v0.1 PNP Achchuthan Shanmugasundram reviewed gene: PNP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe combined immunodeficiency with adenosine deaminase deficiency v0.1 ADA Achchuthan Shanmugasundram reviewed gene: ADA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Segmental or atypical neurofibromatosis type 1 testing v0.1 NF1 Achchuthan Shanmugasundram reviewed gene: NF1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
SCID with features of gamma chain deficiency v0.1 IL2RG Achchuthan Shanmugasundram reviewed gene: IL2RG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sandhoff disease v0.1 HEXB Achchuthan Shanmugasundram reviewed gene: HEXB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinoblastoma v0.1 RB1 Achchuthan Shanmugasundram reviewed gene: RB1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Pulmonary alveolar microlithiasis v0.1 SLC34A2 Achchuthan Shanmugasundram reviewed gene: SLC34A2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
PTEN Hamartoma Tumor Syndrome v0.1 PTEN Achchuthan Shanmugasundram reviewed gene: PTEN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pseudoxanthoma elasticum v0.1 ENPP1 Achchuthan Shanmugasundram reviewed gene: ENPP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Pseudoxanthoma elasticum v0.1 ABCC6 Achchuthan Shanmugasundram reviewed gene: ABCC6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary hyperaldosteronism v0.1 KCNJ5 Achchuthan Shanmugasundram reviewed gene: KCNJ5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
POLG-related disorder v0.1 POLG Achchuthan Shanmugasundram reviewed gene: POLG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenylketonuria v0.1 PAH Achchuthan Shanmugasundram reviewed gene: PAH: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Peutz Jeghers Syndrome v0.1 STK11 Achchuthan Shanmugasundram reviewed gene: STK11: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Nijmegen breakage syndrome v0.1 NBN Achchuthan Shanmugasundram reviewed gene: NBN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Niemann-Pick disease type A or B v0.1 SMPD1 Achchuthan Shanmugasundram reviewed gene: SMPD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Niemann Pick disease type C v0.1 NPC2 Achchuthan Shanmugasundram reviewed gene: NPC2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Niemann Pick disease type C v0.1 NPC1 Achchuthan Shanmugasundram reviewed gene: NPC1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Nevoid Basal Cell Carcinoma Syndrome or Gorlin syndrome v0.1 SUFU Achchuthan Shanmugasundram reviewed gene: SUFU: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Nevoid Basal Cell Carcinoma Syndrome or Gorlin syndrome v0.1 PTCH1 Achchuthan Shanmugasundram reviewed gene: PTCH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Neutropaenia consistent with ELANE variants v0.1 ELANE Achchuthan Shanmugasundram reviewed gene: ELANE: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Neuronal ceroid lipofuscinosis type 2 v0.1 TPP1 Achchuthan Shanmugasundram Deleted their comment
Neuronal ceroid lipofuscinosis type 2 v0.1 TPP1 Achchuthan Shanmugasundram changed review comment from: TPP1 has been added to the panel for R271 Neuronal ceroid lipofuscinosis type 2 with a green rating as agreed with the NHS Genomic Medicine Service.; to: TPP1 has been added to the panel for R271 Neuronal ceroid lipofuscinosis type 2 with a green rating as agreed with the NHS Genomic Medicine Service.
Neuronal ceroid lipofuscinosis type 2 v0.1 TPP1 Achchuthan Shanmugasundram commented on gene: TPP1: TPP1 has been added to the panel for R271 Neuronal ceroid lipofuscinosis type 2 with a green rating as agreed with the NHS Genomic Medicine Service.
Neuronal ceroid lipofuscinosis type 2 v0.1 TPP1 Achchuthan Shanmugasundram reviewed gene: TPP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Neurofibromatosis type 1 (GMS) v0.1 SPRED1 Achchuthan Shanmugasundram reviewed gene: SPRED1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Neurofibromatosis type 1 (GMS) v0.1 NF1 Achchuthan Shanmugasundram reviewed gene: NF1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Neonatal diabetes - small panel v0.1 KCNJ11 Achchuthan Shanmugasundram reviewed gene: KCNJ11: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Neonatal diabetes - small panel v0.1 ABCC8 Achchuthan Shanmugasundram reviewed gene: ABCC8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
NARP syndrome or maternally inherited Leigh syndrome v0.1 MT-ND6 Achchuthan Shanmugasundram reviewed gene: MT-ND6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MITOCHONDRIAL
NARP syndrome or maternally inherited Leigh syndrome v0.1 MT-ATP6 Achchuthan Shanmugasundram reviewed gene: MT-ATP6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MITOCHONDRIAL
Multiple exostoses v0.1 EXT2 Achchuthan Shanmugasundram reviewed gene: EXT2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Multiple exostoses v0.1 EXT1 Achchuthan Shanmugasundram reviewed gene: EXT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Multiple endocrine neoplasia type 2 v0.1 RET Achchuthan Shanmugasundram reviewed gene: RET: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mucopolysaccharidosis type VI v0.1 ARSB Achchuthan Shanmugasundram reviewed gene: ARSB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mucopolysaccharidosis type IVA v0.1 GALNS Achchuthan Shanmugasundram reviewed gene: GALNS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mucopolysaccharidosis type IIIB v0.1 NAGLU Achchuthan Shanmugasundram reviewed gene: NAGLU: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mucopolysaccharidosis type IIIA v0.2 SGSH Achchuthan Shanmugasundram reviewed gene: SGSH: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mucopolysaccharidosis type II v0.1 IDS Achchuthan Shanmugasundram reviewed gene: IDS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mucopolysaccharidosis type IH or S v0.1 IDUA Achchuthan Shanmugasundram reviewed gene: IDUA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mucolipidosis II and III Alpha or Beta v0.1 GNPTAB Achchuthan Shanmugasundram reviewed gene: GNPTAB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monitoring for G(M)CSF escape variants v0.1 CSF3R Achchuthan Shanmugasundram reviewed gene: CSF3R: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial neurogastrointestinal encephalopathy v0.1 TYMP Achchuthan Shanmugasundram reviewed gene: TYMP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial Complex V deficiency, TMEM70 type v0.1 TMEM70 Achchuthan Shanmugasundram reviewed gene: TMEM70: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Lysosomal acid lipase deficiency v0.1 LIPA Achchuthan Shanmugasundram reviewed gene: LIPA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Lymphoproliferative syndrome with absent SAP expression v0.1 SH2D1A Achchuthan Shanmugasundram reviewed gene: SH2D1A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Krabbe disease - Saposin A deficiency v0.1 PSAP Achchuthan Shanmugasundram reviewed gene: PSAP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Krabbe disease - GALC deficiency v0.1 GALC Achchuthan Shanmugasundram reviewed gene: GALC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
IPEX - Immunodysregulation Polyendocrinopathy and Enteropathy, X-Linked v0.1 FOXP3 Achchuthan Shanmugasundram reviewed gene: FOXP3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Inherited susceptibility to acute lymphoblastoid leukaemia (ALL) v0.1 PAX5 Achchuthan Shanmugasundram reviewed gene: PAX5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Inherited susceptibility to acute lymphoblastoid leukaemia (ALL) v0.1 ETV6 Achchuthan Shanmugasundram reviewed gene: ETV6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Inherited parathyroid cancer v0.1 CDC73 Achchuthan Shanmugasundram reviewed gene: CDC73: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Incontinentia pigmenti v0.1 IKBKG Achchuthan Shanmugasundram reviewed gene: IKBKG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Hereditary angioedema types I and II v0.1 SERPING1 Achchuthan Shanmugasundram reviewed gene: SERPING1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Haemophagocytic syndrome with absent XIAP expression v0.1 XIAP Achchuthan Shanmugasundram reviewed gene: XIAP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Haemophagocytic syndrome with absent perforin expression v0.1 PRF1 Achchuthan Shanmugasundram reviewed gene: PRF1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
GM1 Gangliosidosis and Mucopolysaccharidosis Type IVB v0.1 GLB1 Achchuthan Shanmugasundram reviewed gene: GLB1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Glycogen storage disease V v0.1 PYGM Achchuthan Shanmugasundram reviewed gene: PYGM: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Glucokinase-related fasting hyperglycaemia v0.1 GCK Achchuthan Shanmugasundram reviewed gene: GCK: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Generalised arterial calcification in infancy v0.1 ENPP1 Achchuthan Shanmugasundram reviewed gene: ENPP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Generalised arterial calcification in infancy v0.1 ABCC6 Achchuthan Shanmugasundram reviewed gene: ABCC6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Gaucher disease v0.1 GBA Achchuthan Shanmugasundram reviewed gene: GBA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fumarate hydratase-related tumour syndromes v0.1 FH Achchuthan Shanmugasundram reviewed gene: FH: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Familial tumours of the nervous system v0.1 SUFU Achchuthan Shanmugasundram reviewed gene: SUFU: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Familial tumours of the nervous system v0.1 SMARCE1 Achchuthan Shanmugasundram reviewed gene: SMARCE1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Familial tumours of the nervous system v0.1 SMARCB1 Achchuthan Shanmugasundram reviewed gene: SMARCB1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Familial tumours of the nervous system v0.1 NF2 Achchuthan Shanmugasundram reviewed gene: NF2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Familial tumours of the nervous system v0.1 LZTFL1 Achchuthan Shanmugasundram reviewed gene: LZTFL1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Familial tumours of the nervous system v0.1 DGCR8 Achchuthan Shanmugasundram reviewed gene: DGCR8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Familial dysalbuminaemic hyperthyroxinaemia v0.1 ALB Achchuthan Shanmugasundram reviewed gene: ALB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Factor XIII deficiency v0.1 F13B Achchuthan Shanmugasundram reviewed gene: F13B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Factor XIII deficiency v0.1 F13A1 Achchuthan Shanmugasundram reviewed gene: F13A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Factor XI deficiency v0.1 F11 Achchuthan Shanmugasundram reviewed gene: F11: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Factor X deficiency v0.1 F10 Achchuthan Shanmugasundram Deleted their comment
Factor X deficiency v0.1 F10 Achchuthan Shanmugasundram commented on gene: F10: F10 has been added to the panel for R119 Factor X deficiency with a green rating as agreed with the NHS Genomic Medicine Service.
Factor X deficiency v0.1 F10 Achchuthan Shanmugasundram reviewed gene: F10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Factor VIII deficiency v0.1 F8 Achchuthan Shanmugasundram reviewed gene: F8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Factor VII deficiency v0.1 F7 Achchuthan Shanmugasundram reviewed gene: F7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Factor V deficiency v0.1 F5 Achchuthan Shanmugasundram reviewed gene: F5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Factor IX deficiency v0.1 F9 Achchuthan Shanmugasundram reviewed gene: F9: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Factor II deficiency v0.1 F2 Achchuthan Shanmugasundram reviewed gene: F2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Facioscapulohumeral muscular dystrophy - extended testing v0.1 SMCHD1 Achchuthan Shanmugasundram reviewed gene: SMCHD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fabry disease v0.1 GLA Achchuthan Shanmugasundram reviewed gene: GLA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Elastin-related phenotypes v0.1 ELN Achchuthan Shanmugasundram reviewed gene: ELN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Duchenne or Becker muscular dystrophy v0.1 DMD Achchuthan Shanmugasundram reviewed gene: DMD: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
DICER1-related cancer predisposition v0.1 DICER1 Achchuthan Shanmugasundram reviewed gene: DICER1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cystinosis v0.1 CTNS Achchuthan Shanmugasundram reviewed gene: CTNS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cystic fibrosis - Diagnostic v0.1 CFTR Achchuthan Shanmugasundram edited their review of gene: CFTR: Changed rating: GREEN
Cystic fibrosis - Diagnostic v0.1 CFTR Achchuthan Shanmugasundram reviewed gene: CFTR: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital adrenal hyperplasia v0.1 CYP21A2 Achchuthan Shanmugasundram reviewed gene: CYP21A2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Combined vitamin K-dependent clotting factor deficiency v0.1 VKORC1 Achchuthan Shanmugasundram reviewed gene: VKORC1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Combined vitamin K-dependent clotting factor deficiency v0.1 GGCX Achchuthan Shanmugasundram reviewed gene: GGCX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Central congenital hypoventilation v0.1 PHOX2B Achchuthan Shanmugasundram reviewed gene: PHOX2B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Carney complex v0.1 PRKAR1A Achchuthan Shanmugasundram reviewed gene: PRKAR1A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Calcium-sensing receptor phenotypes v0.1 CASR Achchuthan Shanmugasundram reviewed gene: CASR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
CADASIL v0.1 NOTCH3 Achchuthan Shanmugasundram reviewed gene: NOTCH3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Blepharophimosis ptosis and epicanthus inversus v0.1 FOXL2 Achchuthan Shanmugasundram reviewed gene: FOXL2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Beckwith-Wiedemann syndrome v0.1 CDKN1C Achchuthan Shanmugasundram reviewed gene: CDKN1C: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Barth syndrome v0.1 TAZ Achchuthan Shanmugasundram reviewed gene: TAZ: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
BAP1 associated tumour predisposition syndrome v0.2 BAP1 Achchuthan Shanmugasundram reviewed gene: BAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Autoimmune Polyendocrine Syndrome v0.2 AIRE Achchuthan Shanmugasundram edited their review of gene: AIRE: Changed rating: GREEN; Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Autoimmune Polyendocrine Syndrome v0.2 AIRE Achchuthan Shanmugasundram commented on gene: AIRE
von Willebrand disease v0.1 VWF Achchuthan Shanmugasundram gene: VWF was added
gene: VWF was added to von Willebrand disease. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: VWF was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Wiskott-Aldrich syndrome v0.1 WAS Achchuthan Shanmugasundram gene: WAS was added
gene: WAS was added to Wiskott-Aldrich syndrome. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: WAS was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Wilson disease v0.1 ATP7B Achchuthan Shanmugasundram gene: ATP7B was added
gene: ATP7B was added to Wilson disease. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: ATP7B was set to BIALLELIC, autosomal or pseudoautosomal
Von Hippel Lindau syndrome v0.1 VHL Achchuthan Shanmugasundram gene: VHL was added
gene: VHL was added to Von Hippel Lindau syndrome. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: VHL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Variegate porphyria v0.1 PPOX Achchuthan Shanmugasundram gene: PPOX was added
gene: PPOX was added to Variegate porphyria. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: PPOX was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Tuberous sclerosis v0.1 TSC2 Achchuthan Shanmugasundram gene: TSC2 was added
gene: TSC2 was added to Tuberous sclerosis. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: TSC2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Tuberous sclerosis v0.1 TSC1 Achchuthan Shanmugasundram gene: TSC1 was added
gene: TSC1 was added to Tuberous sclerosis. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: TSC1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Thiamine metabolism dysfunction syndrome 2 v0.1 SLC19A3 Achchuthan Shanmugasundram gene: SLC19A3 was added
gene: SLC19A3 was added to Thiamine metabolism dysfunction syndrome 2. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: SLC19A3 was set to BIALLELIC, autosomal or pseudoautosomal
Thanatophoric dysplasia v0.1 FGFR3 Achchuthan Shanmugasundram gene: FGFR3 was added
gene: FGFR3 was added to Thanatophoric dysplasia. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: FGFR3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sickle cell, thalassaemia and other haemoglobinopathies v0.1 HBB Achchuthan Shanmugasundram gene: HBB was added
gene: HBB was added to Thalassaemia and other haemoglobinopathies. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: HBB was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sickle cell, thalassaemia and other haemoglobinopathies v0.1 HBA1 Achchuthan Shanmugasundram gene: HBA1 was added
gene: HBA1 was added to Thalassaemia and other haemoglobinopathies. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: HBA1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Tay-Sachs disease v0.1 HEXA Achchuthan Shanmugasundram gene: HEXA was added
gene: HEXA was added to Tay-Sachs disease. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: HEXA was set to BIALLELIC, autosomal or pseudoautosomal
Syndromic and non syndromic craniosynostosis involving midline sutures v0.1 SMAD6 Achchuthan Shanmugasundram gene: SMAD6 was added
gene: SMAD6 was added to Syndromic and non syndromic craniosynostosis involving midline sutures. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: SMAD6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Subcutaneous panniculitis T-cell lymphoma (SPTCL) v0.1 HAVCR2 Achchuthan Shanmugasundram gene: HAVCR2 was added
gene: HAVCR2 was added to Subcutaneous panniculitis T-cell lymphoma (SPTCL). Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: HAVCR2 was set to BIALLELIC, autosomal or pseudoautosomal
Spinal muscular atrophy - Diagnostic v0.1 SMN1 Achchuthan Shanmugasundram gene: SMN1 was added
gene: SMN1 was added to Spinal muscular atrophy type 1 rare mutation testing. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: SMN1 was set to BIALLELIC, autosomal or pseudoautosomal
Smith-Lemli-Opitz syndrome v0.1 DHCR7 Achchuthan Shanmugasundram gene: DHCR7 was added
gene: DHCR7 was added to Smith-Lemli-Opitz syndrome. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: DHCR7 was set to BIALLELIC, autosomal or pseudoautosomal
Sitosterolaemia v0.1 ABCG8 Achchuthan Shanmugasundram gene: ABCG8 was added
gene: ABCG8 was added to Sitosterolaemia. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: ABCG8 was set to BIALLELIC, autosomal or pseudoautosomal
Sitosterolaemia v0.1 ABCG5 Achchuthan Shanmugasundram gene: ABCG5 was added
gene: ABCG5 was added to Sitosterolaemia. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: ABCG5 was set to BIALLELIC, autosomal or pseudoautosomal
Short stature - SHOX deficiency v0.1 SHOX Achchuthan Shanmugasundram gene: SHOX was added
gene: SHOX was added to Short stature - SHOX deficiency. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: SHOX was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Severe combined immunodeficiency with PNP deficiency v0.1 PNP Achchuthan Shanmugasundram gene: PNP was added
gene: PNP was added to Severe combined immunodeficiency with PNP deficiency. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: PNP was set to BIALLELIC, autosomal or pseudoautosomal
Severe combined immunodeficiency with adenosine deaminase deficiency v0.1 ADA Achchuthan Shanmugasundram gene: ADA was added
gene: ADA was added to Severe combined immunodeficiency with adenosine deaminase deficiency. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: ADA was set to BIALLELIC, autosomal or pseudoautosomal
Segmental or atypical neurofibromatosis type 1 testing v0.1 NF1 Achchuthan Shanmugasundram gene: NF1 was added
gene: NF1 was added to Segmental or atypical neurofibromatosis type 1 testing. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: NF1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
SCID with features of gamma chain deficiency v0.1 IL2RG Achchuthan Shanmugasundram gene: IL2RG was added
gene: IL2RG was added to SCID with features of gamma chain deficiency. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: IL2RG was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sandhoff disease v0.1 HEXB Achchuthan Shanmugasundram gene: HEXB was added
gene: HEXB was added to Sandhoff disease. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: HEXB was set to BIALLELIC, autosomal or pseudoautosomal
Retinoblastoma v0.1 RB1 Achchuthan Shanmugasundram gene: RB1 was added
gene: RB1 was added to Retinoblastoma. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: RB1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenylketonuria v0.1 PAH Achchuthan Shanmugasundram gene: PAH was added
gene: PAH was added to Phenylketonuria. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: PAH was set to BIALLELIC, autosomal or pseudoautosomal
Pulmonary alveolar microlithiasis v0.1 SLC34A2 Achchuthan Shanmugasundram gene: SLC34A2 was added
gene: SLC34A2 was added to Pulmonary alveolar microlithiasis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: SLC34A2 was set to BIALLELIC, autosomal or pseudoautosomal
PTEN Hamartoma Tumor Syndrome v0.1 PTEN Achchuthan Shanmugasundram gene: PTEN was added
gene: PTEN was added to PTEN Hamartoma Tumor Syndrome. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: PTEN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pseudoxanthoma elasticum v0.1 ENPP1 Achchuthan Shanmugasundram gene: ENPP1 was added
gene: ENPP1 was added to Pseudoxanthoma elasticum. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: ENPP1 was set to BIALLELIC, autosomal or pseudoautosomal
Pseudoxanthoma elasticum v0.1 ABCC6 Achchuthan Shanmugasundram gene: ABCC6 was added
gene: ABCC6 was added to Pseudoxanthoma elasticum. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: ABCC6 was set to BIALLELIC, autosomal or pseudoautosomal
Primary hyperaldosteronism v0.1 KCNJ5 Achchuthan Shanmugasundram gene: KCNJ5 was added
gene: KCNJ5 was added to Primary hyperaldosteronism - KCNJ5. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: KCNJ5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
POLG-related disorder v0.1 POLG Achchuthan Shanmugasundram gene: POLG was added
gene: POLG was added to POLG-related disorder. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: POLG was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Peutz Jeghers Syndrome v0.1 STK11 Achchuthan Shanmugasundram gene: STK11 was added
gene: STK11 was added to Peutz Jeghers Syndrome. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: STK11 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Nevoid Basal Cell Carcinoma Syndrome or Gorlin syndrome v0.1 SUFU Achchuthan Shanmugasundram gene: SUFU was added
gene: SUFU was added to Nevoid Basal Cell Carcinoma Syndrome or Gorlin syndrome. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: SUFU was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Nevoid Basal Cell Carcinoma Syndrome or Gorlin syndrome v0.1 PTCH1 Achchuthan Shanmugasundram gene: PTCH1 was added
gene: PTCH1 was added to Nevoid Basal Cell Carcinoma Syndrome or Gorlin syndrome. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: PTCH1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Nijmegen breakage syndrome v0.1 NBN Achchuthan Shanmugasundram gene: NBN was added
gene: NBN was added to Nijmegen breakage syndrome. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: NBN was set to BIALLELIC, autosomal or pseudoautosomal
Niemann-Pick disease type A or B v0.1 SMPD1 Achchuthan Shanmugasundram gene: SMPD1 was added
gene: SMPD1 was added to Niemann-Pick disease type A or B. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: SMPD1 was set to BIALLELIC, autosomal or pseudoautosomal
Niemann Pick disease type C v0.1 NPC2 Achchuthan Shanmugasundram gene: NPC2 was added
gene: NPC2 was added to Niemann Pick disease type C. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: NPC2 was set to BIALLELIC, autosomal or pseudoautosomal
Niemann Pick disease type C v0.1 NPC1 Achchuthan Shanmugasundram gene: NPC1 was added
gene: NPC1 was added to Niemann Pick disease type C. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: NPC1 was set to BIALLELIC, autosomal or pseudoautosomal
Neutropaenia consistent with ELANE variants v0.1 ELANE Achchuthan Shanmugasundram gene: ELANE was added
gene: ELANE was added to Neutropaenia consistent with ELANE mutations. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: ELANE was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Neuronal ceroid lipofuscinosis type 2 v0.1 TPP1 Achchuthan Shanmugasundram gene: TPP1 was added
gene: TPP1 was added to Neuronal ceroid lipofuscinosis type 2. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: TPP1 was set to BIALLELIC, autosomal or pseudoautosomal
Neurofibromatosis type 1 (GMS) v0.1 SPRED1 Achchuthan Shanmugasundram gene: SPRED1 was added
gene: SPRED1 was added to Neurofibromatosis type 1 (GMS). Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: SPRED1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Neurofibromatosis type 1 (GMS) v0.1 NF1 Achchuthan Shanmugasundram gene: NF1 was added
gene: NF1 was added to Neurofibromatosis type 1 (GMS). Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: NF1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Neonatal diabetes - small panel v0.1 KCNJ11 Achchuthan Shanmugasundram gene: KCNJ11 was added
gene: KCNJ11 was added to Neonatal diabetes - small panel. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: KCNJ11 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Neonatal diabetes - small panel v0.1 ABCC8 Achchuthan Shanmugasundram gene: ABCC8 was added
gene: ABCC8 was added to Neonatal diabetes - small panel. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: ABCC8 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
NARP syndrome or maternally inherited Leigh syndrome v0.1 MT-ND6 Achchuthan Shanmugasundram gene: MT-ND6 was added
gene: MT-ND6 was added to NARP syndrome or maternally inherited Leigh syndrome. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene gene: MT-ND6 was set to MITOCHONDRIAL
NARP syndrome or maternally inherited Leigh syndrome v0.1 MT-ATP6 Achchuthan Shanmugasundram gene: MT-ATP6 was added
gene: MT-ATP6 was added to NARP syndrome or maternally inherited Leigh syndrome. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene gene: MT-ATP6 was set to MITOCHONDRIAL
Multiple exostoses v0.1 EXT2 Achchuthan Shanmugasundram gene: EXT2 was added
gene: EXT2 was added to Multiple exostoses. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: EXT2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Multiple exostoses v0.1 EXT1 Achchuthan Shanmugasundram gene: EXT1 was added
gene: EXT1 was added to Multiple exostoses. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: EXT1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Multiple endocrine neoplasia type 2 v0.1 RET Achchuthan Shanmugasundram gene: RET was added
gene: RET was added to Multiple endocrine neoplasia type 2. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: RET was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mucopolysaccharidosis type II v0.1 IDS Achchuthan Shanmugasundram gene: IDS was added
gene: IDS was added to Mucopolysaccharidosis type II. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: IDS was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mucopolysaccharidosis type VI v0.1 ARSB Achchuthan Shanmugasundram gene: ARSB was added
gene: ARSB was added to Mucopolysaccharidosis type VI. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: ARSB was set to BIALLELIC, autosomal or pseudoautosomal
Mucopolysaccharidosis type IVA v0.1 GALNS Achchuthan Shanmugasundram gene: GALNS was added
gene: GALNS was added to Mucopolysaccharidosis type IVA. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: GALNS was set to BIALLELIC, autosomal or pseudoautosomal
Mucopolysaccharidosis type IIIB v0.1 NAGLU Achchuthan Shanmugasundram gene: NAGLU was added
gene: NAGLU was added to Mucopolysaccharidosis type IIIB. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: NAGLU was set to BIALLELIC, autosomal or pseudoautosomal
Mucopolysaccharidosis type IIIA v0.1 SGSH Achchuthan Shanmugasundram gene: SGSH was added
gene: SGSH was added to Mucopolysaccharidosis type IIIA. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: SGSH was set to BIALLELIC, autosomal or pseudoautosomal
Mucopolysaccharidosis type IH or S v0.1 IDUA Achchuthan Shanmugasundram gene: IDUA was added
gene: IDUA was added to Mucopolysaccharidosis type IH/S. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: IDUA was set to BIALLELIC, autosomal or pseudoautosomal
Mucolipidosis II and III Alpha or Beta v0.1 GNPTAB Achchuthan Shanmugasundram gene: GNPTAB was added
gene: GNPTAB was added to Mucolipidosis II and III Alpha/Beta. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: GNPTAB was set to BIALLELIC, autosomal or pseudoautosomal
Monitoring for G(M)CSF escape variants v0.1 CSF3R Achchuthan Shanmugasundram gene: CSF3R was added
gene: CSF3R was added to Monitoring for G(M)CSF escape mutations. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: CSF3R was set to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial neurogastrointestinal encephalopathy v0.1 TYMP Achchuthan Shanmugasundram gene: TYMP was added
gene: TYMP was added to Mitochondrial neurogastrointestinal encephalopathy. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: TYMP was set to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial Complex V deficiency, TMEM70 type v0.1 TMEM70 Achchuthan Shanmugasundram gene: TMEM70 was added
gene: TMEM70 was added to Mitochondrial Complex V deficiency, TMEM70 type. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: TMEM70 was set to BIALLELIC, autosomal or pseudoautosomal
Lysosomal acid lipase deficiency v0.1 LIPA Achchuthan Shanmugasundram gene: LIPA was added
gene: LIPA was added to Lysosomal acid lipase deficiency. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: LIPA was set to BIALLELIC, autosomal or pseudoautosomal
Lymphoproliferative syndrome with absent SAP expression v0.1 SH2D1A Achchuthan Shanmugasundram gene: SH2D1A was added
gene: SH2D1A was added to Lymphoproliferative syndrome with absent SAP expression. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: SH2D1A was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Krabbe disease - Saposin A deficiency v0.1 PSAP Achchuthan Shanmugasundram gene: PSAP was added
gene: PSAP was added to Krabbe disease - Saposin A deficiency. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: PSAP was set to BIALLELIC, autosomal or pseudoautosomal
Krabbe disease - GALC deficiency v0.1 GALC Achchuthan Shanmugasundram gene: GALC was added
gene: GALC was added to Krabbe disease - GALC deficiency. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: GALC was set to BIALLELIC, autosomal or pseudoautosomal
Inherited susceptibility to acute lymphoblastoid leukaemia (ALL) v0.1 PAX5 Achchuthan Shanmugasundram gene: PAX5 was added
gene: PAX5 was added to Inherited susceptibility to acute lymphoblastoid leukaemia (ALL). Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: PAX5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Inherited susceptibility to acute lymphoblastoid leukaemia (ALL) v0.1 ETV6 Achchuthan Shanmugasundram gene: ETV6 was added
gene: ETV6 was added to Inherited susceptibility to acute lymphoblastoid leukaemia (ALL). Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: ETV6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Neurodegenerative disorders, adult onset v4.28 FXN_GAA Sarah Leigh Tag Q3_23_promote_green tag was added to STR: FXN_GAA.
Neurodegenerative disorders, adult onset v4.28 FXN_GAA Sarah Leigh edited their review of STR: FXN_GAA: Added comment: It is recommended this STR be promoted to Green following GMS review, as the testing method for this clinicial indication is now WGS.; Changed rating: GREEN
IPEX - Immunodysregulation Polyendocrinopathy and Enteropathy, X-Linked v0.1 FOXP3 Achchuthan Shanmugasundram gene: FOXP3 was added
gene: FOXP3 was added to IPEX - Immunodysregulation Polyendocrinopathy and Enteropathy, X-Linked. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: FOXP3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Inherited parathyroid cancer v0.1 CDC73 Achchuthan Shanmugasundram gene: CDC73 was added
gene: CDC73 was added to Inherited parathyroid cancer. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: CDC73 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Inherited breast cancer and ovarian cancer v2.7 RAD51D Achchuthan Shanmugasundram Source NHS GMS was added to RAD51D.
Inherited breast cancer and ovarian cancer v2.7 RAD51C Achchuthan Shanmugasundram Source NHS GMS was added to RAD51C.
Incontinentia pigmenti v0.1 IKBKG Achchuthan Shanmugasundram gene: IKBKG was added
gene: IKBKG was added to Incontinentia pigmenti. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: IKBKG was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Hereditary angioedema types I and II v0.1 SERPING1 Achchuthan Shanmugasundram gene: SERPING1 was added
gene: SERPING1 was added to Hereditary angioedema types I and II. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: SERPING1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Haemophagocytic syndrome with absent XIAP expression v0.1 XIAP Achchuthan Shanmugasundram gene: XIAP was added
gene: XIAP was added to Haemophagocytic syndrome with absent XIAP expression. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: XIAP was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Haemophagocytic syndrome with absent perforin expression v0.1 PRF1 Achchuthan Shanmugasundram gene: PRF1 was added
gene: PRF1 was added to Haemophagocytic syndrome with absent perforin expression. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: PRF1 was set to BIALLELIC, autosomal or pseudoautosomal
GM1 Gangliosidosis and Mucopolysaccharidosis Type IVB v0.1 GLB1 Achchuthan Shanmugasundram gene: GLB1 was added
gene: GLB1 was added to GM1 Gangliosidosis and Mucopolysaccharidosis Type IVB. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: GLB1 was set to BIALLELIC, autosomal or pseudoautosomal
Glycogen storage disease V v0.1 PYGM Achchuthan Shanmugasundram gene: PYGM was added
gene: PYGM was added to Glycogen storage disease V. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: PYGM was set to BIALLELIC, autosomal or pseudoautosomal
Glucokinase-related fasting hyperglycaemia v0.1 GCK Achchuthan Shanmugasundram gene: GCK was added
gene: GCK was added to Glucokinase-related fasting hyperglycaemia. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: GCK was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Generalised arterial calcification in infancy v0.1 ENPP1 Achchuthan Shanmugasundram gene: ENPP1 was added
gene: ENPP1 was added to Generalised arterial calcification in infancy. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: ENPP1 was set to BIALLELIC, autosomal or pseudoautosomal
Generalised arterial calcification in infancy v0.1 ABCC6 Achchuthan Shanmugasundram gene: ABCC6 was added
gene: ABCC6 was added to Generalised arterial calcification in infancy. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: ABCC6 was set to BIALLELIC, autosomal or pseudoautosomal
Gaucher disease v0.1 GBA Achchuthan Shanmugasundram gene: GBA was added
gene: GBA was added to Gaucher disease. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: GBA was set to BIALLELIC, autosomal or pseudoautosomal
Fumarate hydratase-related tumour syndromes v0.1 FH Achchuthan Shanmugasundram gene: FH was added
gene: FH was added to Fumarate hydratase-related tumour syndromes. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: FH was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Familial tumours of the nervous system v0.1 SUFU Achchuthan Shanmugasundram gene: SUFU was added
gene: SUFU was added to Familial tumours of the nervous system. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: SUFU was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Familial tumours of the nervous system v0.1 SMARCE1 Achchuthan Shanmugasundram gene: SMARCE1 was added
gene: SMARCE1 was added to Familial tumours of the nervous system. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: SMARCE1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Familial tumours of the nervous system v0.1 SMARCB1 Achchuthan Shanmugasundram gene: SMARCB1 was added
gene: SMARCB1 was added to Familial tumours of the nervous system. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: SMARCB1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Familial tumours of the nervous system v0.1 NF2 Achchuthan Shanmugasundram gene: NF2 was added
gene: NF2 was added to Familial tumours of the nervous system. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: NF2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Familial tumours of the nervous system v0.1 LZTFL1 Achchuthan Shanmugasundram gene: LZTFL1 was added
gene: LZTFL1 was added to Familial tumours of the nervous system. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: LZTFL1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Familial tumours of the nervous system v0.1 DGCR8 Achchuthan Shanmugasundram gene: DGCR8 was added
gene: DGCR8 was added to Familial tumours of the nervous system. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: DGCR8 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary spastic paraplegia, adult onset v3.10 ATXN10_ATTCT Sarah Leigh Tag Q3_23_promote_green tag was added to STR: ATXN10_ATTCT.
Familial dysalbuminaemic hyperthyroxinaemia v0.1 ALB Achchuthan Shanmugasundram gene: ALB was added
gene: ALB was added to Familial dysalbuminaemic hyperthyroxinaemia. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: ALB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary spastic paraplegia, adult onset v3.10 ATXN10_ATTCT Sarah Leigh reviewed STR: ATXN10_ATTCT: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Factor XIII deficiency v0.1 F13B Achchuthan Shanmugasundram gene: F13B was added
gene: F13B was added to Factor XIII deficiency. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: F13B was set to BIALLELIC, autosomal or pseudoautosomal
Factor XIII deficiency v0.1 F13A1 Achchuthan Shanmugasundram gene: F13A1 was added
gene: F13A1 was added to Factor XIII deficiency. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: F13A1 was set to BIALLELIC, autosomal or pseudoautosomal
Dystonia, chorea or related movement disorder, adult onset v3.4 PPP2R2B_CAG Sarah Leigh Tag Q3_23_promote_green tag was added to STR: PPP2R2B_CAG.
Factor XI deficiency v0.1 F11 Achchuthan Shanmugasundram gene: F11 was added
gene: F11 was added to Factor XI deficiency. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: F11 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Dystonia, chorea or related movement disorder, adult onset v3.4 CACNA1A_CAG Sarah Leigh Tag Q3_23_promote_green tag was added to STR: CACNA1A_CAG.
Factor X deficiency v0.1 F10 Achchuthan Shanmugasundram gene: F10 was added
gene: F10 was added to Factor X deficiency. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: F10 was set to BIALLELIC, autosomal or pseudoautosomal
Dystonia, chorea or related movement disorder, adult onset v3.4 ATXN3_CAG Sarah Leigh Tag Q3_23_promote_green tag was added to STR: ATXN3_CAG.
Factor VIII deficiency v0.1 F8 Achchuthan Shanmugasundram gene: F8 was added
gene: F8 was added to Factor VIII deficiency. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: F8 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Dystonia, chorea or related movement disorder, adult onset v3.4 ATXN2_CAG Sarah Leigh Tag Q3_23_promote_green tag was added to STR: ATXN2_CAG.
Factor VII deficiency v0.1 F7 Achchuthan Shanmugasundram gene: F7 was added
gene: F7 was added to Factor VII deficiency. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: F7 was set to BIALLELIC, autosomal or pseudoautosomal
Dystonia, chorea or related movement disorder, adult onset v3.4 ATXN1_CAG Sarah Leigh Tag Q3_23_promote_green tag was added to STR: ATXN1_CAG.
Dystonia, chorea or related movement disorder, adult onset v3.4 CSTB_CCCCGCCCCGCG Sarah Leigh Tag Q3_23_promote_green tag was added to STR: CSTB_CCCCGCCCCGCG.
Dystonia, chorea or related movement disorder, adult onset v3.4 PPP2R2B_CAG Sarah Leigh reviewed STR: PPP2R2B_CAG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Dystonia, chorea or related movement disorder, adult onset v3.4 CACNA1A_CAG Sarah Leigh reviewed STR: CACNA1A_CAG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Factor V deficiency v0.1 F5 Achchuthan Shanmugasundram gene: F5 was added
gene: F5 was added to Factor V deficiency. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: F5 was set to BIALLELIC, autosomal or pseudoautosomal
Dystonia, chorea or related movement disorder, adult onset v3.4 ATXN3_CAG Sarah Leigh reviewed STR: ATXN3_CAG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Factor IX deficiency v0.1 F9 Achchuthan Shanmugasundram gene: F9 was added
gene: F9 was added to Factor IX deficiency. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: F9 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Dystonia, chorea or related movement disorder, adult onset v3.4 ATXN2_CAG Sarah Leigh reviewed STR: ATXN2_CAG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Factor II deficiency v0.1 F2 Achchuthan Shanmugasundram gene: F2 was added
gene: F2 was added to Factor II deficiency. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: F2 was set to BIALLELIC, autosomal or pseudoautosomal
Dystonia, chorea or related movement disorder, adult onset v3.4 ATXN1_CAG Sarah Leigh reviewed STR: ATXN1_CAG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Dystonia, chorea or related movement disorder, adult onset v3.4 CSTB_CCCCGCCCCGCG Sarah Leigh edited their review of STR: CSTB_CCCCGCCCCGCG: Added comment: It is recommended this STR be promoted to Green following GMS review, as the testing method for this clinicial indication is now WGS.; Changed rating: GREEN
Facioscapulohumeral muscular dystrophy - extended testing v0.1 SMCHD1 Achchuthan Shanmugasundram gene: SMCHD1 was added
gene: SMCHD1 was added to Facioscapulohumeral muscular dystrophy - extended testing. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: SMCHD1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fabry disease v0.1 GLA Achchuthan Shanmugasundram gene: GLA was added
gene: GLA was added to Fabry disease. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: GLA was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Elastin-related phenotypes v0.1 ELN Achchuthan Shanmugasundram gene: ELN was added
gene: ELN was added to Elastin-related phenotypes. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: ELN was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Duchenne or Becker muscular dystrophy v0.1 DMD Achchuthan Shanmugasundram gene: DMD was added
gene: DMD was added to Duchenne or Becker muscular dystrophy. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: DMD was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
DICER1-related cancer predisposition v0.1 DICER1 Achchuthan Shanmugasundram gene: DICER1 was added
gene: DICER1 was added to DICER1-related cancer predisposition. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: DICER1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Neurodegenerative disorders, adult onset v4.28 NOP56_GGCCTG Sarah Leigh Tag Q3_23_promote_green tag was added to STR: NOP56_GGCCTG.
Neurodegenerative disorders, adult onset v4.28 PPP2R2B_CAG Sarah Leigh Tag Q3_23_promote_green tag was added to STR: PPP2R2B_CAG.
Neurodegenerative disorders, adult onset v4.28 CSTB_CCCCGCCCCGCG Sarah Leigh Tag Q3_23_promote_green tag was added to STR: CSTB_CCCCGCCCCGCG.
Neurodegenerative disorders, adult onset v4.28 CACNA1A_CAG Sarah Leigh Tag Q3_23_promote_green tag was added to STR: CACNA1A_CAG.
Neurodegenerative disorders, adult onset v4.28 ATXN7_CAG Sarah Leigh Tag Q3_23_promote_green tag was added to STR: ATXN7_CAG.
Neurodegenerative disorders, adult onset v4.28 ATXN3_CAG Sarah Leigh Tag Q3_23_promote_green tag was added to STR: ATXN3_CAG.
Neurodegenerative disorders, adult onset v4.28 ATXN2_CAG Sarah Leigh Tag Q3_23_promote_green tag was added to STR: ATXN2_CAG.
Neurodegenerative disorders, adult onset v4.28 ATXN1_CAG Sarah Leigh Tag Q3_23_promote_green tag was added to STR: ATXN1_CAG.
Neurodegenerative disorders, adult onset v4.28 ATXN10_ATTCT Sarah Leigh Tag Q3_23_promote_green tag was added to STR: ATXN10_ATTCT.
Neurodegenerative disorders, adult onset v4.28 TBP_CAG Sarah Leigh Tag Q3_23_promote_green tag was added to STR: TBP_CAG.
Neurodegenerative disorders, adult onset v4.28 JPH3_CTG Sarah Leigh Tag Q3_23_promote_green tag was added to STR: JPH3_CTG.
Neurodegenerative disorders, adult onset v4.28 PPP2R2B_CAG Sarah Leigh changed review comment from: It is recommended this STR be promoted to Green following GMS review as the testing method for this clinicial indication is now WGS.; to: It is recommended this STR be promoted to Green following GMS review, as the testing method for this clinicial indication is now WGS.
Neurodegenerative disorders, adult onset v4.28 PPP2R2B_CAG Sarah Leigh changed review comment from: It is recommended this STR be promoted to Green following GMS review as the testing method for this clinicial indication is now WGS.; to: It is recommended this STR be promoted to Green following GMS review as the testing method for this clinicial indication is now WGS.
Neurodegenerative disorders, adult onset v4.28 JPH3_CTG Sarah Leigh changed review comment from: It is recommended this STR be promoted to Green following GMS review as the testing method for this clinicial indication is now WGS.; to: It is recommended this STR be promoted to Green following GMS review, as the testing method for this clinicial indication is now WGS.
Neurodegenerative disorders, adult onset v4.28 CSTB_CCCCGCCCCGCG Sarah Leigh changed review comment from: It is recommended this STR be promoted to Green following GMS review as the testing method for this clinicial indication is now WGS.; to: It is recommended this STR be promoted to Green following GMS review, as the testing method for this clinicial indication is now WGS.
Neurodegenerative disorders, adult onset v4.28 CSTB_CCCCGCCCCGCG Sarah Leigh changed review comment from: It is recommended this STR be promoted to Green following GMS review as the testing method for this clinicial indication is now WGS.; to: It is recommended this STR be promoted to Green following GMS review as the testing method for this clinicial indication is now WGS.
Neurodegenerative disorders, adult onset v4.28 CACNA1A_CAG Sarah Leigh changed review comment from: It is recommended this STR be promoted to Green following GMS review as the testing method for this clinicial indication is now WGS.; to: It is recommended this STR be promoted to Green following GMS review as the testing method for this clinicial indication is now WGS.
Neurodegenerative disorders, adult onset v4.28 ATXN7_CAG Sarah Leigh changed review comment from: It is recommended this STR be promoted to Green following GMS review as the testing method for this clinicial indication is now WGS.; to: It is recommended this STR be promoted to Green following GMS review, as the testing method for this clinicial indication is now WGS.
Neurodegenerative disorders, adult onset v4.28 ATXN3_CAG Sarah Leigh changed review comment from: It is recommended this STR be promoted to Green following GMS review as the testing method for this clinicial indication is now WGS.; to: It is recommended this STR be promoted to Green following GMS review, as the testing method for this clinicial indication is now WGS.
Neurodegenerative disorders, adult onset v4.28 ATXN2_CAG Sarah Leigh changed review comment from: It is recommended this STR be promoted to Green following GMS review as the testing method for this clinicial indication is now WGS.; to: It is recommended this STR be promoted to Green following GMS review, as the testing method for this clinicial indication is now WGS.
Neurodegenerative disorders, adult onset v4.28 ATXN1_CAG Sarah Leigh changed review comment from: It is recommended this STR be promoted to Green following GMS review as the testing method for this clinicial indication is now WGS.; to: It is recommended this STR be promoted to Green following GMS review, as the testing method for this clinicial indication is now WGS.
Neurodegenerative disorders, adult onset v4.28 ATXN10_ATTCT Sarah Leigh changed review comment from: It is recommended this STR be promoted to Green following GMS review as the testing method for this clinicial indication is now WGS.; to: It is recommended this STR be promoted to Green following GMS review, as the testing method for this clinicial indication is now WGS.
Neurodegenerative disorders, adult onset v4.28 TBP_CAG Sarah Leigh changed review comment from: It is recommended this STR be promoted to Green following GMS review as the testing method for this clinicial indication is now WGS.; to: It is recommended this STR be promoted to Green following GMS review, as the testing method for this clinicial indication is now WGS.
Neurodegenerative disorders, adult onset v4.28 JPH3_CTG Sarah Leigh changed review comment from: It is recommended this STR be promoted to Green following GMS review as the testing method for this clinicial indication is now WGS.; to: It is recommended this STR be promoted to Green following GMS review, as the testing method for this clinicial indication is now WGS.
Neurodegenerative disorders, adult onset v4.28 NOP56_GGCCTG Sarah Leigh reviewed STR: NOP56_GGCCTG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Neurodegenerative disorders, adult onset v4.28 PPP2R2B_CAG Sarah Leigh reviewed STR: PPP2R2B_CAG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Neurodegenerative disorders, adult onset v4.28 JPH3_CTG Sarah Leigh commented on STR: JPH3_CTG: It is recommended this STR be promoted to Green following GMS review as the testing method for this clinicial indication is now WGS.
Neurodegenerative disorders, adult onset v4.28 CSTB_CCCCGCCCCGCG Sarah Leigh edited their review of STR: CSTB_CCCCGCCCCGCG: Added comment: It is recommended this STR be promoted to Green following GMS review as the testing method for this clinicial indication is now WGS.; Changed rating: GREEN
Neurodegenerative disorders, adult onset v4.28 CACNA1A_CAG Sarah Leigh reviewed STR: CACNA1A_CAG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Neurodegenerative disorders, adult onset v4.28 ATXN7_CAG Sarah Leigh reviewed STR: ATXN7_CAG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Neurodegenerative disorders, adult onset v4.28 ATXN3_CAG Sarah Leigh reviewed STR: ATXN3_CAG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Neurodegenerative disorders, adult onset v4.28 ATXN2_CAG Sarah Leigh reviewed STR: ATXN2_CAG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Neurodegenerative disorders, adult onset v4.28 ATXN1_CAG Sarah Leigh reviewed STR: ATXN1_CAG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Neurodegenerative disorders, adult onset v4.28 ATXN10_ATTCT Sarah Leigh reviewed STR: ATXN10_ATTCT: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Neurodegenerative disorders, adult onset v4.28 TBP_CAG Sarah Leigh reviewed STR: TBP_CAG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Neurodegenerative disorders, adult onset v4.28 JPH3_CTG Sarah Leigh edited their review of STR: JPH3_CTG: Added comment: It is recommended this STR be promoted to Green following GMS review as the testing method for this clinicial indication is now WGS.; Changed rating: GREEN
Neurodegenerative disorders, adult onset v4.28 ATN1_CAG Sarah Leigh Tag Q3_23_promote_green tag was added to STR: ATN1_CAG.
Neurodegenerative disorders, adult onset v4.28 ATN1_CAG Sarah Leigh reviewed STR: ATN1_CAG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Cystinosis v0.1 CTNS Achchuthan Shanmugasundram gene: CTNS was added
gene: CTNS was added to Cystinosis. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: CTNS was set to BIALLELIC, autosomal or pseudoautosomal
Cystic fibrosis - Diagnostic v0.1 CFTR Achchuthan Shanmugasundram gene: CFTR was added
gene: CFTR was added to Cystic fibrosis diagnostic test. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: CFTR was set to BIALLELIC, autosomal or pseudoautosomal
Congenital adrenal hyperplasia v0.1 CYP21A2 Achchuthan Shanmugasundram gene: CYP21A2 was added
gene: CYP21A2 was added to Congenital adrenal hyperplasia diagnostic test. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: CYP21A2 was set to BIALLELIC, autosomal or pseudoautosomal
Combined vitamin K-dependent clotting factor deficiency v0.1 VKORC1 Achchuthan Shanmugasundram gene: VKORC1 was added
gene: VKORC1 was added to Combined vitamin K-dependent clotting factor deficiency. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: VKORC1 was set to BIALLELIC, autosomal or pseudoautosomal
Combined vitamin K-dependent clotting factor deficiency v0.1 GGCX Achchuthan Shanmugasundram gene: GGCX was added
gene: GGCX was added to Combined vitamin K-dependent clotting factor deficiency. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: GGCX was set to BIALLELIC, autosomal or pseudoautosomal
Central congenital hypoventilation v0.1 PHOX2B Achchuthan Shanmugasundram gene: PHOX2B was added
gene: PHOX2B was added to Central congenital hypoventilation. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: PHOX2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Carney complex v0.1 PRKAR1A Achchuthan Shanmugasundram gene: PRKAR1A was added
gene: PRKAR1A was added to Carney complex. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: PRKAR1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Calcium-sensing receptor phenotypes v0.1 CASR Achchuthan Shanmugasundram gene: CASR was added
gene: CASR was added to Calcium-sensing receptor phenotypes. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: CASR was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
CADASIL v0.1 NOTCH3 Achchuthan Shanmugasundram gene: NOTCH3 was added
gene: NOTCH3 was added to CADASIL. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: NOTCH3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Blepharophimosis ptosis and epicanthus inversus v0.1 FOXL2 Achchuthan Shanmugasundram gene: FOXL2 was added
gene: FOXL2 was added to Blepharophimosis ptosis and epicanthus inversus. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: FOXL2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Beckwith-Wiedemann syndrome v0.1 CDKN1C Achchuthan Shanmugasundram gene: CDKN1C was added
gene: CDKN1C was added to Beckwith-Wiedemann syndrome. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: CDKN1C was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Barth syndrome v0.1 TAZ Achchuthan Shanmugasundram gene: TAZ was added
gene: TAZ was added to Barth syndrome. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: TAZ was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
BAP1 associated tumour predisposition syndrome v0.2 BAP1 Achchuthan Shanmugasundram gene: BAP1 was added
gene: BAP1 was added to BAP1 associated tumour predisposition syndrome. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: BAP1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Autoimmune Polyendocrine Syndrome v0.2 AIRE Achchuthan Shanmugasundram gene: AIRE was added
gene: AIRE was added to Autoimmune Polyendocrine Syndrome. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: AIRE was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Agammaglobulinaemia with absent BTK expression v0.7 Achchuthan Shanmugasundram Panel types changed to GMS Rare Disease
Acute intermittent porphyria v0.8 Achchuthan Shanmugasundram Panel types changed to GMS Rare Disease
Autoimmune lymphoproliferative syndrome with defective apoptosis v0.6 Achchuthan Shanmugasundram Panel types changed to GMS Rare Disease
Ataxia telangiectasia - mutation testing v0.7 Achchuthan Shanmugasundram Panel types changed to GMS Rare Disease
APC associated Polyposis v0.8 Achchuthan Shanmugasundram Panel types changed to GMS Rare Disease
Alveolar capillary dysplasia with misalignment of pulmonary veins v0.6 Achchuthan Shanmugasundram Panel types changed to GMS Rare Disease
Alstrom syndrome v0.6 Achchuthan Shanmugasundram Panel types changed to GMS Rare Disease
Albright hereditary osteodystrophy, pseudohypoparathyroidism, pseudopseudohypoparathyroidism, acrodysostosis and osteoma cutis v0.7 Achchuthan Shanmugasundram Panel types changed to GMS Rare Disease
Wiskott-Aldrich syndrome v0.0 Achchuthan Shanmugasundram Added Panel Wiskott-Aldrich syndrome
Set list of related panels to R20
Set panel types to: GMS Rare Disease
Wilson disease v0.0 Achchuthan Shanmugasundram Added Panel Wilson disease
Set list of related panels to R172
Set panel types to: GMS Rare Disease
von Willebrand disease v0.0 Achchuthan Shanmugasundram Added Panel von Willebrand disease
Set list of related panels to R121
Set panel types to: GMS Rare Disease
Von Hippel Lindau syndrome v0.0 Achchuthan Shanmugasundram Added Panel Von Hippel Lindau syndrome
Set list of related panels to R225
Set panel types to: GMS Rare Disease
Variegate porphyria v0.0 Achchuthan Shanmugasundram Added Panel Variegate porphyria
Set list of related panels to R170
Set panel types to: GMS Rare Disease
Tuberous sclerosis v0.0 Achchuthan Shanmugasundram Added Panel Tuberous sclerosis
Set list of related panels to R228
Set panel types to: GMS Rare Disease
Thiamine metabolism dysfunction syndrome 2 v0.0 Achchuthan Shanmugasundram Added Panel Thiamine metabolism dysfunction syndrome 2
Set list of related panels to R395
Set panel types to: GMS Rare Disease
Thanatophoric dysplasia v0.0 Achchuthan Shanmugasundram Added Panel Thanatophoric dysplasia
Set list of related panels to R25
Set panel types to: GMS Rare Disease
Sickle cell, thalassaemia and other haemoglobinopathies v0.0 Achchuthan Shanmugasundram Added Panel Thalassaemia and other haemoglobinopathies
Set list of related panels to R93
Set panel types to: GMS Rare Disease
Tay-Sachs disease v0.0 Achchuthan Shanmugasundram Added Panel Tay-Sachs disease
Set list of related panels to R286
Set panel types to: GMS Rare Disease
Syndromic and non syndromic craniosynostosis involving midline sutures v0.0 Achchuthan Shanmugasundram Added Panel Syndromic and non syndromic craniosynostosis involving midline sutures
Set list of related panels to R416
Set panel types to: GMS Rare Disease
Subcutaneous panniculitis T-cell lymphoma (SPTCL) v0.0 Achchuthan Shanmugasundram Added Panel Subcutaneous panniculitis T-cell lymphoma (SPTCL)
Set list of related panels to R424
Set panel types to: GMS Rare Disease
Spinal muscular atrophy - Diagnostic v0.0 Achchuthan Shanmugasundram Added Panel Spinal muscular atrophy type 1 rare mutation testing
Set list of related panels to R71
Set panel types to: GMS Rare Disease
Smith-Lemli-Opitz syndrome v0.0 Achchuthan Shanmugasundram Added Panel Smith-Lemli-Opitz syndrome
Set list of related panels to R270
Set panel types to: GMS Rare Disease
Sitosterolaemia v0.0 Achchuthan Shanmugasundram Added Panel Sitosterolaemia
Set list of related panels to R323
Set panel types to: GMS Rare Disease
Short stature - SHOX deficiency v0.0 Achchuthan Shanmugasundram Added Panel Short stature - SHOX deficiency
Set list of related panels to R52
Set panel types to: GMS Rare Disease
Severe combined immunodeficiency with PNP deficiency v0.0 Achchuthan Shanmugasundram Added Panel Severe combined immunodeficiency with PNP deficiency
Set list of related panels to R234
Set panel types to: GMS Rare Disease
Severe combined immunodeficiency with adenosine deaminase deficiency v0.0 Achchuthan Shanmugasundram Added Panel Severe combined immunodeficiency with adenosine deaminase deficiency
Set list of related panels to R16
Set panel types to: GMS Rare Disease
Segmental or atypical neurofibromatosis type 1 testing v0.0 Achchuthan Shanmugasundram Added Panel Segmental or atypical neurofibromatosis type 1 testing
Set list of related panels to R376
Set panel types to: GMS Rare Disease
SCID with features of gamma chain deficiency v0.0 Achchuthan Shanmugasundram Added Panel SCID with features of gamma chain deficiency
Set list of related panels to R235
Set panel types to: GMS Rare Disease
Sandhoff disease v0.0 Achchuthan Shanmugasundram Added Panel Sandhoff disease
Set list of related panels to R285
Set panel types to: GMS Rare Disease
Retinoblastoma v0.0 Achchuthan Shanmugasundram Added Panel Retinoblastoma
Set list of related panels to R219
Set panel types to: GMS Rare Disease
Pulmonary alveolar microlithiasis v0.0 Achchuthan Shanmugasundram Added Panel Pulmonary alveolar microlithiasis
Set list of related panels to R426
Set panel types to: GMS Rare Disease
PTEN Hamartoma Tumor Syndrome v0.0 Achchuthan Shanmugasundram Added Panel PTEN Hamartoma Tumor Syndrome
Set list of related panels to R213
Set panel types to: GMS Rare Disease
Pseudoxanthoma elasticum v0.0 Achchuthan Shanmugasundram Added Panel Pseudoxanthoma elasticum
Set list of related panels to R420
Set panel types to: GMS Rare Disease
Primary hyperaldosteronism v0.0 Achchuthan Shanmugasundram Added Panel Primary hyperaldosteronism - KCNJ5
Set list of related panels to R344
Set panel types to: GMS Rare Disease
POLG-related disorder v0.0 Achchuthan Shanmugasundram Added Panel POLG-related disorder
Set list of related panels to R315
Set panel types to: GMS Rare Disease
Phenylketonuria v0.0 Achchuthan Shanmugasundram Added Panel Phenylketonuria
Set list of related panels to R283
Set panel types to: GMS Rare Disease
Peutz Jeghers Syndrome v0.0 Achchuthan Shanmugasundram Added Panel Peutz Jeghers Syndrome
Set list of related panels to R212
Set panel types to: GMS Rare Disease
Nijmegen breakage syndrome v0.0 Achchuthan Shanmugasundram Added Panel Nijmegen breakage syndrome
Set list of related panels to R259.2
Set panel types to: GMS Rare Disease
Niemann-Pick disease type A or B v0.0 Achchuthan Shanmugasundram Added Panel Niemann-Pick disease type A or B
Set list of related panels to R282
Set panel types to: GMS Rare Disease
Niemann Pick disease type C v0.0 Achchuthan Shanmugasundram Added Panel Niemann Pick disease type C
Set list of related panels to R380
Set panel types to: GMS Rare Disease
Nevoid Basal Cell Carcinoma Syndrome or Gorlin syndrome v0.0 Achchuthan Shanmugasundram Added Panel Nevoid Basal Cell Carcinoma Syndrome or Gorlin syndrome
Set list of related panels to R214
Set panel types to: GMS Rare Disease
Neutropaenia consistent with ELANE variants v0.0 Achchuthan Shanmugasundram Added Panel Neutropaenia consistent with ELANE mutations
Set list of related panels to R313
Set panel types to: GMS Rare Disease
Neuronal ceroid lipofuscinosis type 2 v0.0 Achchuthan Shanmugasundram Added Panel Neuronal ceroid lipofuscinosis type 2
Set list of related panels to R271
Set panel types to: GMS Rare Disease
Neurofibromatosis type 1 (GMS) v0.0 Achchuthan Shanmugasundram Added Panel Neurofibromatosis type 1 (GMS)
Set list of related panels to R222
Set panel types to: GMS Rare Disease
Neonatal diabetes - small panel v0.0 Achchuthan Shanmugasundram Added Panel Neonatal diabetes - small panel
Set list of related panels to R143
Set panel types to: GMS Rare Disease
NARP syndrome or maternally inherited Leigh syndrome v0.0 Achchuthan Shanmugasundram Added Panel NARP syndrome or maternally inherited Leigh syndrome
Set list of related panels to R351
Set panel types to: GMS Rare Disease
Multiple exostoses v0.0 Achchuthan Shanmugasundram Added Panel Multiple exostoses
Set list of related panels to R390
Set panel types to: GMS Rare Disease
Multiple endocrine neoplasia type 2 v0.0 Achchuthan Shanmugasundram Added Panel Multiple endocrine neoplasia type 2
Set list of related panels to R218
Set panel types to: GMS Rare Disease
Mucopolysaccharidosis type VI v0.0 Achchuthan Shanmugasundram Added Panel Mucopolysaccharidosis type VI
Set list of related panels to R290
Set panel types to: GMS Rare Disease
Mucopolysaccharidosis type IVA v0.0 Achchuthan Shanmugasundram Added Panel Mucopolysaccharidosis type IVA
Set list of related panels to R287
Set panel types to: GMS Rare Disease
Mucopolysaccharidosis type IIIB v0.0 Achchuthan Shanmugasundram Added Panel Mucopolysaccharidosis type IIIB
Set list of related panels to R292
Set panel types to: GMS Rare Disease
Mucopolysaccharidosis type IIIA v0.0 Achchuthan Shanmugasundram Added Panel Mucopolysaccharidosis type IIIA
Set list of related panels to R291
Set panel types to: GMS Rare Disease
Mucopolysaccharidosis type II v0.0 Achchuthan Shanmugasundram Added Panel Mucopolysaccharidosis type II
Set list of related panels to R278
Set panel types to: GMS Rare Disease
Mucopolysaccharidosis type IH or S v0.0 Achchuthan Shanmugasundram Added Panel Mucopolysaccharidosis type IH/S
Set list of related panels to R277
Set panel types to: GMS Rare Disease
Mucolipidosis II and III Alpha or Beta v0.0 Achchuthan Shanmugasundram Added Panel Mucolipidosis II and III Alpha/Beta
Set list of related panels to R289
Set panel types to: GMS Rare Disease
Monitoring for G(M)CSF escape variants v0.0 Achchuthan Shanmugasundram Added Panel Monitoring for G(M)CSF escape mutations
Set list of related panels to R338
Set panel types to: GMS Rare Disease
Mitochondrial neurogastrointestinal encephalopathy v0.0 Achchuthan Shanmugasundram Added Panel Mitochondrial neurogastrointestinal encephalopathy
Set list of related panels to R394
Set panel types to: GMS Rare Disease
Mitochondrial Complex V deficiency, TMEM70 type v0.0 Achchuthan Shanmugasundram Added Panel Mitochondrial Complex V deficiency, TMEM70 type
Set list of related panels to R396
Set panel types to: GMS Rare Disease
Lysosomal acid lipase deficiency v0.0 Achchuthan Shanmugasundram Added Panel Lysosomal acid lipase deficiency
Set list of related panels to R325
Set panel types to: GMS Rare Disease
Lymphoproliferative syndrome with absent SAP expression v0.0 Achchuthan Shanmugasundram Added Panel Lymphoproliferative syndrome with absent SAP expression
Set list of related panels to R17
Set panel types to: GMS Rare Disease
Krabbe disease - Saposin A deficiency v0.0 Achchuthan Shanmugasundram Added Panel Krabbe disease - Saposin A deficiency
Set list of related panels to R281
Set panel types to: GMS Rare Disease
Krabbe disease - GALC deficiency v0.0 Achchuthan Shanmugasundram Added Panel Krabbe disease - GALC deficiency
Set list of related panels to R280
Set panel types to: GMS Rare Disease
IPEX - Immunodysregulation Polyendocrinopathy and Enteropathy, X-Linked v0.0 Achchuthan Shanmugasundram Added Panel IPEX - Immunodysregulation Polyendocrinopathy and Enteropathy, X-Linked
Set list of related panels to R157
Set panel types to: GMS Rare Disease
Inherited susceptibility to acute lymphoblastoid leukaemia (ALL) v0.0 Achchuthan Shanmugasundram Added Panel Inherited susceptibility to acute lymphoblastoid leukaemia (ALL)
Set list of related panels to R366
Set panel types to: GMS Rare Disease
Inherited parathyroid cancer v0.0 Achchuthan Shanmugasundram Added Panel Inherited parathyroid cancer
Set list of related panels to R226
Set panel types to: GMS Rare Disease
Incontinentia pigmenti v0.0 Achchuthan Shanmugasundram Added Panel Incontinentia pigmenti
Set list of related panels to R239
Set panel types to: GMS Rare Disease
Hereditary angioedema types I and II v0.0 Achchuthan Shanmugasundram Added Panel Hereditary angioedema types I and II
Set list of related panels to R341
Set panel types to: GMS Rare Disease
Haemophagocytic syndrome with absent XIAP expression v0.0 Achchuthan Shanmugasundram Added Panel Haemophagocytic syndrome with absent XIAP expression
Set list of related panels to R18
Set panel types to: GMS Rare Disease
Haemophagocytic syndrome with absent perforin expression v0.0 Achchuthan Shanmugasundram Added Panel Haemophagocytic syndrome with absent perforin expression
Set list of related panels to R232
Set panel types to: GMS Rare Disease
GM1 Gangliosidosis and Mucopolysaccharidosis Type IVB v0.0 Achchuthan Shanmugasundram Added Panel GM1 Gangliosidosis and Mucopolysaccharidosis Type IVB
Set list of related panels to R288
Set panel types to: GMS Rare Disease
Glycogen storage disease V v0.0 Achchuthan Shanmugasundram Added Panel Glycogen storage disease V
Set list of related panels to R273
Set panel types to: GMS Rare Disease
Glucokinase-related fasting hyperglycaemia v0.0 Achchuthan Shanmugasundram Added Panel Glucokinase-related fasting hyperglycaemia
Set list of related panels to R142
Set panel types to: GMS Rare Disease
Generalised arterial calcification in infancy v0.0 Achchuthan Shanmugasundram Added Panel Generalised arterial calcification in infancy
Set list of related panels to R384
Set panel types to: GMS Rare Disease
Gaucher disease v0.0 Achchuthan Shanmugasundram Added Panel Gaucher disease
Set list of related panels to R272
Set panel types to: GMS Rare Disease
Fumarate hydratase-related tumour syndromes v0.0 Achchuthan Shanmugasundram Added Panel Fumarate hydratase-related tumour syndromes
Set list of related panels to R365
Set panel types to: GMS Rare Disease
Familial tumours of the nervous system v0.0 Achchuthan Shanmugasundram Added Panel Familial tumours of the nervous system
Set list of related panels to R221
Set panel types to: GMS Rare Disease
Familial dysalbuminaemic hyperthyroxinaemia v0.0 Achchuthan Shanmugasundram Added Panel Familial dysalbuminaemic hyperthyroxinaemia
Set list of related panels to R329
Set panel types to: GMS Rare Disease
Factor XIII deficiency v0.0 Achchuthan Shanmugasundram Added Panel Factor XIII deficiency
Set list of related panels to R122
Set panel types to: GMS Rare Disease
Factor XI deficiency v0.0 Achchuthan Shanmugasundram Added Panel Factor XI deficiency
Set list of related panels to R120
Set panel types to: GMS Rare Disease
Factor X deficiency v0.0 Achchuthan Shanmugasundram Added Panel Factor X deficiency
Set list of related panels to R119
Set panel types to: GMS Rare Disease
Factor VIII deficiency v0.0 Achchuthan Shanmugasundram Added Panel Factor VIII deficiency
Set list of related panels to R117
Set panel types to: GMS Rare Disease
Factor VII deficiency v0.0 Achchuthan Shanmugasundram Added Panel Factor VII deficiency
Set list of related panels to R116
Set panel types to: GMS Rare Disease
Factor V deficiency v0.0 Achchuthan Shanmugasundram Added Panel Factor V deficiency
Set list of related panels to R115
Set panel types to: GMS Rare Disease
Factor IX deficiency v0.0 Achchuthan Shanmugasundram Added Panel Factor IX deficiency
Set list of related panels to R118
Set panel types to: GMS Rare Disease
Factor II deficiency v0.0 Achchuthan Shanmugasundram Added Panel Factor II deficiency
Set list of related panels to R112
Set panel types to: GMS Rare Disease
Facioscapulohumeral muscular dystrophy - extended testing v0.0 Achchuthan Shanmugasundram Added Panel Facioscapulohumeral muscular dystrophy - extended testing
Set list of related panels to R345
Set panel types to: GMS Rare Disease
Fabry disease v0.0 Achchuthan Shanmugasundram Added Panel Fabry disease
Set list of related panels to R335
Set panel types to: GMS Rare Disease
Elastin-related phenotypes v0.0 Achchuthan Shanmugasundram Added Panel Elastin-related phenotypes
Set list of related panels to R140
Set panel types to: GMS Rare Disease
Duchenne or Becker muscular dystrophy v0.0 Achchuthan Shanmugasundram Added Panel Duchenne or Becker muscular dystrophy
Set list of related panels to R73
Set panel types to: GMS Rare Disease
DICER1-related cancer predisposition v0.0 Achchuthan Shanmugasundram Added Panel DICER1-related cancer predisposition
Set list of related panels to R364
Set panel types to: GMS Rare Disease
Cystinosis v0.0 Achchuthan Shanmugasundram Added Panel Cystinosis
Set list of related panels to R334
Set panel types to: GMS Rare Disease
Cystic fibrosis - Diagnostic v0.0 Achchuthan Shanmugasundram Added Panel Cystic fibrosis diagnostic test
Set list of related panels to R184
Set panel types to: GMS Rare Disease
Congenital adrenal hyperplasia v0.0 Achchuthan Shanmugasundram Added Panel Congenital adrenal hyperplasia diagnostic test
Set list of related panels to R180
Set panel types to: GMS Rare Disease
Combined vitamin K-dependent clotting factor deficiency v0.0 Achchuthan Shanmugasundram Added Panel Combined vitamin K-dependent clotting factor deficiency
Set list of related panels to R123
Set panel types to: GMS Rare Disease
Central congenital hypoventilation v0.0 Achchuthan Shanmugasundram Added Panel Central congenital hypoventilation
Set list of related panels to R333
Set panel types to: GMS Rare Disease
Carney complex v0.0 Achchuthan Shanmugasundram Added Panel Carney complex
Set list of related panels to R156
Set panel types to: GMS Rare Disease
Calcium-sensing receptor phenotypes v0.0 Achchuthan Shanmugasundram Added Panel Calcium-sensing receptor phenotypes
Set list of related panels to R319
Set panel types to: GMS Rare Disease
CADASIL v0.0 Achchuthan Shanmugasundram Added Panel CADASIL
Set list of related panels to R337
Set panel types to: GMS Rare Disease
Blepharophimosis ptosis and epicanthus inversus v0.0 Achchuthan Shanmugasundram Added Panel Blepharophimosis ptosis and epicanthus inversus
Set list of related panels to R43
Set panel types to: GMS Rare Disease
Beckwith-Wiedemann syndrome v0.0 Achchuthan Shanmugasundram Added Panel Beckwith-Wiedemann syndrome
Set list of related panels to R49.3
Set panel types to: GMS Rare Disease
Barth syndrome v0.0 Achchuthan Shanmugasundram Added Panel Barth syndrome
Set list of related panels to R391
Set panel types to: GMS Rare Disease
BAP1 associated tumour predisposition syndrome v0.1 Achchuthan Shanmugasundram Panel types changed to GMS Rare Disease
Autoimmune Polyendocrine Syndrome v0.1 Achchuthan Shanmugasundram Panel types changed to GMS Rare Disease
Early onset or syndromic epilepsy v4.62 KDM6B Hannah Robinson gene: KDM6B was added
gene: KDM6B was added to Early onset or syndromic epilepsy. Sources: NHS GMS
Mode of inheritance for gene: KDM6B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KDM6B were set to PMID: 37196654
Phenotypes for gene: KDM6B were set to Global developmental delay; Intellectual disability; Hypotonia; Joint hypermobility; seizures; Overgrowth
Penetrance for gene: KDM6B were set to Incomplete
Review for gene: KDM6B was set to GREEN
gene: KDM6B was marked as current diagnostic
Added comment: Information from Rots et al. 2023 (PMID:37196654): According to OMIM, heterozygous variants in KDM6B cause “neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities.” Here, by examining the molecular and clinical spectrum of 85 reported individuals with mostly de novo (likely) pathogenic KDM6B variants, we demonstrate that this description is inaccurate and potentially misleading. Cognitive deficits are seen consistently in all individuals, but the overall phenotype is highly variable. Notably, coarse facies and distal skeletal anomalies, as defined by OMIM, are rare in this expanded cohort while other features are unexpectedly common (e.g., hypotonia, psychosis, etc.).

In this cohort, 9/69 (13%) of individuals had seizures.

The majority of individuals had de novo variants but 9/85 individuals inherited the variant (five maternal, four paternal) from a mildly affected (developmental delay [DD], learning problems, autism spectrum disorder [ASD]) or clinically unaffected parent.
Sources: NHS GMS
Neuronal ceroid lipofuscinosis v2.2 CLCN6 Sarah Leigh edited their review of gene: CLCN6: Added comment: PMIDs: 16950870 & 21107136 report the characterization of CLCN6 deficient mouse model, which display some features of neuronal ceroid lipofuscinosis. PMID: 16950870 identifies two heterozygous CLCN6 variants (p.V580M, p.T628R) in 2/75 patients with late-onset neuronal ceroid lipofuscinosis, however, the authors concluded that there was insufficient evidence for these variants being responsible for the phenotype in the patients.; Changed rating: AMBER; Changed publications to: 21107136, 33217309, 16950870
Neuronal ceroid lipofuscinosis v2.2 CLCN6 Sarah Leigh Publications for gene: CLCN6 were set to 29667327; 26658788; 25794116; 21107136; 33217309
Clefting v4.78 UBE3B Achchuthan Shanmugasundram Classified gene: UBE3B as Amber List (moderate evidence)
Clefting v4.78 UBE3B Achchuthan Shanmugasundram Gene: ube3b has been classified as Amber List (Moderate Evidence).
Clefting v4.77 UBE3B Achchuthan Shanmugasundram gene: UBE3B was added
gene: UBE3B was added to Clefting. Sources: Literature
Mode of inheritance for gene: UBE3B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UBE3B were set to 23200864; 23687348; 37010288
Phenotypes for gene: UBE3B were set to Kaufman oculocerebrofacial syndrome, OMIM:244450
Review for gene: UBE3B was set to AMBER
Added comment: PMID:23687348 - One of two patients reported with biallelic variants in UBE3B in this study and one of four patients reported in PMID:23200864 and reviewed here had submucous cleft palate.

DECIPHER database - One of three patients with homozygous sequence variants in UBE3B had median cleft palate.
Sources: Literature
Clefting v4.76 TCF12 Achchuthan Shanmugasundram gene: TCF12 was added
gene: TCF12 was added to Clefting. Sources: Literature
Mode of inheritance for gene: TCF12 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TCF12 were set to 23354436; 31353793; 37010288
Phenotypes for gene: TCF12 were set to Craniosynostosis 3, OMIM:615314
Review for gene: TCF12 was set to RED
Added comment: Clefting has only been rarely reported in patients with TCF12 variants and hence this gene should be rated red.

PMID:23354436 - One of 73 individuals (from 38 families) reported with craniosynostosis and identified with heterozygous variants in TCF12 gene had cleft lip and cleft palate.

PMID:31353793 - Of two cases reported with heterozygous TCF12 variants, one had hidden cleft palate.

DECIPHER database - One of 11 patients with heterozygous sequence variants in TCF12 had bifid uvula.
Sources: Literature
Clefting v4.75 SOX11 Achchuthan Shanmugasundram gene: SOX11 was added
gene: SOX11 was added to Clefting. Sources: Literature
Mode of inheritance for gene: SOX11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOX11 were set to 29437512; 37010288
Phenotypes for gene: SOX11 were set to Intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, OMIM:615866
Review for gene: SOX11 was set to RED
Added comment: Cleft palate is a minor clinical indication that is only observed in <10% of patients with SOX11 variants. Hence, this gene should be rated red.

PMID:29437512 - A 14-year-old boy with a phenotype resembling mild Coffin-Siris syndrome and identified with heterozygous SOX11 variant had cleft palate. However, cleft palate was not present in any of the previously reported patients (12 cases) reviewed in this publication.

DECIPHER database - Of 12 patients with heterozygous sequence variants in SOX11 gene, only one patient had cleft soft palate.
Sources: Literature
Clefting v4.74 SMARCB1 Achchuthan Shanmugasundram Deleted their comment
Clefting v4.74 SMARCB1 Achchuthan Shanmugasundram Deleted their comment
Clefting v4.74 SMARCB1 Achchuthan Shanmugasundram Deleted their comment
Clefting v4.74 SMARCB1 Achchuthan Shanmugasundram Classified gene: SMARCB1 as Amber List (moderate evidence)
Clefting v4.74 SMARCB1 Achchuthan Shanmugasundram Added comment: Comment on list classification: Although there are 3 unrelated cases in total, these represent only a minor fraction of patients (from total of 23) reported with SMARCB1 variants. Hence, this gene should be rated amber.
Clefting v4.74 SMARCB1 Achchuthan Shanmugasundram Gene: smarcb1 has been classified as Amber List (Moderate Evidence).
Clefting v4.74 SMARCB1 Achchuthan Shanmugasundram Deleted their comment
Clefting v4.74 SMARCB1 Achchuthan Shanmugasundram Classified gene: SMARCB1 as Amber List (moderate evidence)
Clefting v4.74 SMARCB1 Achchuthan Shanmugasundram Added comment: Comment on list classification: Although there are 3 unrelated cases in total, these represent only a minor fraction of patients (from total of 23) reported with SMARCB1 variants. Hence, this gene should be rated amber.
Clefting v4.74 SMARCB1 Achchuthan Shanmugasundram Gene: smarcb1 has been classified as Amber List (Moderate Evidence).
Clefting v4.74 SMARCB1 Achchuthan Shanmugasundram Classified gene: SMARCB1 as Amber List (moderate evidence)
Clefting v4.74 SMARCB1 Achchuthan Shanmugasundram Added comment: Comment on list classification: Although there are 3 unrelated cases in total, these represent only a minor fraction of patients (from total of 23) reported with SMARCB1 variants. Hence, this gene should be rated amber.
Clefting v4.74 SMARCB1 Achchuthan Shanmugasundram Gene: smarcb1 has been classified as Amber List (Moderate Evidence).
Clefting v4.74 SMARCB1 Achchuthan Shanmugasundram Classified gene: SMARCB1 as Amber List (moderate evidence)
Clefting v4.74 SMARCB1 Achchuthan Shanmugasundram Added comment: Comment on list classification: Although there are 3 unrelated cases in total, these represent only a minor fraction of patients (from total of 23) reported with SMARCB1 variants. Hence, this gene should be rated amber.
Clefting v4.74 SMARCB1 Achchuthan Shanmugasundram Gene: smarcb1 has been classified as Amber List (Moderate Evidence).
Clefting v4.73 SMARCB1 Achchuthan Shanmugasundram Classified gene: SMARCB1 as Red List (low evidence)
Clefting v4.73 SMARCB1 Achchuthan Shanmugasundram Added comment: Comment on list classification: Although there are 3 unrelated cases in total, these represent only a minor fraction of patients (from total of 23) reported with SMARCB1 variants. Hence, this gene should be rated amber.
Clefting v4.73 SMARCB1 Achchuthan Shanmugasundram Gene: smarcb1 has been classified as Red List (Low Evidence).
Clefting v4.72 SMARCB1 Achchuthan Shanmugasundram gene: SMARCB1 was added
gene: SMARCB1 was added to Clefting. Sources: Literature
Mode of inheritance for gene: SMARCB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMARCB1 were set to 25168959; 37010288
Phenotypes for gene: SMARCB1 were set to Coffin-Siris syndrome 3, OMIM:614608
Review for gene: SMARCB1 was set to AMBER
Added comment: PMID:25168959 - Two of ten patients reported with Coffin-Siris syndrome and heterozygous variants in SMARCB1 had cleft palate.

DECIPHER database - One of 13 patients identified with heterozygous sequence variants in SMARCB1 had cleft palate.
Sources: Literature
Clefting v4.71 SIN3A Achchuthan Shanmugasundram gene: SIN3A was added
gene: SIN3A was added to Clefting. Sources: Literature
Mode of inheritance for gene: SIN3A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SIN3A were set to 33437032; 37010288
Phenotypes for gene: SIN3A were set to Witteveen-Kolk syndrome, OMIM:613406
Review for gene: SIN3A was set to RED
Added comment: Clefting was reported only in a minor fraction of patients (<10%) and hence should be rated red.

PMID:33437032 - Of 28 patients with heterozugous variants in SIN3A gene, one patient had submucous cleft hard palate and another with deletion variant had orofacial cleft (both these are reported in DECIPHER database).

DECIPHER database - In addition to the above mentioned patients, one with heterozygous sequence variant had submucous cleft soft panel (from 31 in total), while an additional patient with deletion had cleft hard palate (from 54 patients with CNV variants).
Sources: Literature
Clefting v4.70 PUF60 Achchuthan Shanmugasundram changed review comment from: PMID:24140112 - One patient identified with heterozygous variant in PUF60 gene (p.His169Tyr) had cleft palate.

PMID:27804958 - Five patients were reported with sequence variants in PUF60 gene and none of them had cleft lip/ palate as one of the clinical presentations.

DECIPHER database - Of 27 patients with heterozygous sequence variants in PUF60, only one had submucous cleft hard palate.
Sources: Literature; to: Clefting has only been identified in a minor fraction of patients with monoallelic variants in PUF60 gene and hence this gene should be rated red in this panel.

PMID:24140112 - One patient identified with heterozygous variant in PUF60 gene (p.His169Tyr) had cleft palate.

PMID:27804958 - Five patients were reported with sequence variants in PUF60 gene and none of them had cleft lip/ palate as one of the clinical presentations.

DECIPHER database - Of 27 patients with heterozygous sequence variants in PUF60, only one had submucous cleft hard palate.
Sources: Literature
Clefting v4.70 PUF60 Achchuthan Shanmugasundram gene: PUF60 was added
gene: PUF60 was added to Clefting. Sources: Literature
Mode of inheritance for gene: PUF60 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PUF60 were set to 24140112; 27804958; 37010288
Phenotypes for gene: PUF60 were set to Verheij syndrome, OMIM:615583
Review for gene: PUF60 was set to RED
Added comment: PMID:24140112 - One patient identified with heterozygous variant in PUF60 gene (p.His169Tyr) had cleft palate.

PMID:27804958 - Five patients were reported with sequence variants in PUF60 gene and none of them had cleft lip/ palate as one of the clinical presentations.

DECIPHER database - Of 27 patients with heterozygous sequence variants in PUF60, only one had submucous cleft hard palate.
Sources: Literature
Clefting v4.69 POLR2A Achchuthan Shanmugasundram gene: POLR2A was added
gene: POLR2A was added to Clefting. Sources: Literature
Mode of inheritance for gene: POLR2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POLR2A were set to 31353023; 37010288
Phenotypes for gene: POLR2A were set to Neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities, OMIM:618603
Review for gene: POLR2A was set to RED
Added comment: This gene should be rated red as clefting has only been reported in a minor fraction of patients with monoallelic variants in POLR2A.

PMID:31353023 - 16 individuals were identified with heterozygous variants in POLR2A, of which only one patient had cleft lip.

DECIPHER database - Of 14 patients with heterozygous sequence variants, one had cleft palate and another had bifid uvula.
Sources: Literature
Clefting v4.68 POLA1 Achchuthan Shanmugasundram changed review comment from: PMID:3100651 - Nine patients from five unrelated families were identified with POLA1 variants, of which one patient from family C (has two reported patients) was reported with bifid uvula.

DECIPHER database - One of two patients with hemizygous sequence variants had bifid uvula.
Sources: Literature; to: Bifid uvula is a minor clinical indication that is only found in two patients with POLA1 variants and it is not fully penetrant in the family. Hence, this gene should be rated red.

PMID:3100651 - Nine patients from five unrelated families were identified with POLA1 variants, of which one patient from family C (has two reported patients) was reported with bifid uvula.

DECIPHER database - One of two patients with hemizygous sequence variants had bifid uvula.
Sources: Literature
Clefting v4.68 POLA1 Achchuthan Shanmugasundram gene: POLA1 was added
gene: POLA1 was added to Clefting. Sources: Literature
Mode of inheritance for gene: POLA1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: POLA1 were set to 31006512; 37010288
Review for gene: POLA1 was set to RED
Added comment: PMID:3100651 - Nine patients from five unrelated families were identified with POLA1 variants, of which one patient from family C (has two reported patients) was reported with bifid uvula.

DECIPHER database - One of two patients with hemizygous sequence variants had bifid uvula.
Sources: Literature
Clefting v4.67 NOTCH2 Achchuthan Shanmugasundram Publications for gene: NOTCH2 were set to 9188663; 30329210; 37010288
Clefting v4.67 NOTCH2 Achchuthan Shanmugasundram Publications for gene: NOTCH2 were set to 9188663; 30329210
Clefting v4.66 NOTCH2 Achchuthan Shanmugasundram edited their review of gene: NOTCH2: Changed publications to: 9188663, 30329210, 37010288
Clefting v4.66 NOTCH2 Achchuthan Shanmugasundram Classified gene: NOTCH2 as Amber List (moderate evidence)
Clefting v4.66 NOTCH2 Achchuthan Shanmugasundram Added comment: Comment on list classification: Although there are three cases reported with cleft lip/ palate or cleft of uvula, these are reported only in a minor proportion of patients and hence this gene can only be rated amber.
Clefting v4.66 NOTCH2 Achchuthan Shanmugasundram Gene: notch2 has been classified as Amber List (Moderate Evidence).
Clefting v4.65 NOTCH2 Achchuthan Shanmugasundram gene: NOTCH2 was added
gene: NOTCH2 was added to Clefting. Sources: Literature
Mode of inheritance for gene: NOTCH2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NOTCH2 were set to 9188663; 30329210
Phenotypes for gene: NOTCH2 were set to Hajdu-Cheney syndrome, OMIM:102500
Review for gene: NOTCH2 was set to AMBER
Added comment: PMID:9188663 - An 8.5-year-old boy with NOTCH2 variant and Hajdu-Cheney syndrome was reported with cleft lip and palate.

PMID:30329210 - A 32-year-old male patient with a de novo truncating variant in NOTCH2 and presenting with Hajdu-Cheney syndrome had high arched palate and cleft of uvula.

DECIPHER database - One of seven patients with heterozygous sequence variants in NOTCH2 was identified with submucous cleft hard palate.
Sources: Literature
Intellectual disability v5.191 PSMC3 Dmitrijs Rots gene: PSMC3 was added
gene: PSMC3 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: PSMC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PSMC3 were set to PMID: 37256937
Phenotypes for gene: PSMC3 were set to neurodevelopmental delay
Mode of pathogenicity for gene: PSMC3 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: PSMC3 was set to GREEN
Added comment: 23 individuals with NDD due to 15 different de novo missense variants in PMID: 37256937.
Sources: Literature
Clefting v4.64 MAGEL2 Achchuthan Shanmugasundram gene: MAGEL2 was added
gene: MAGEL2 was added to Clefting. Sources: Literature
Mode of inheritance for gene: MAGEL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAGEL2 were set to 31397880; 37010288
Phenotypes for gene: MAGEL2 were set to Schaaf-Yang syndrome, OMIM:615547
Review for gene: MAGEL2 was set to RED
Added comment: Cleft palate is a minor feature of Schaaf-Yang syndrome and is present only in less than 10% of cases. Hence, this gene should be rated red.

PMID:31397880 - One of five patients presented in this study with heterozygous variants in MAGEL2 gene had cleft palate.

DECIPHER database - One of 20 patients with heterozygous sequence variants in MAGEL2 had cleft palate.
Sources: Literature
Clefting v4.63 EP300 Achchuthan Shanmugasundram changed review comment from: This gene should be rated red as clefting has only been reported in a very small fraction of patients (<5%) identified with monoallleic variants in EP300.

PMID:27648933 - One of 52 patients with Rubinstein-Taybi syndrome caused by monoallelic variants in EP300 gene had cleft lip and palate.

DECIPHER database - Of 58 patients with heterozygous sequence variants in EP300, cleft palate, orofacial cleft and bifid uvula were found in one patient each.
Sources: Literature; to: This gene should be rated red as clefting has only been reported in a very small fraction of patients (<5%) identified with monoallelic variants in EP300.

PMID:27648933 - One of 52 patients with Rubinstein-Taybi syndrome caused by monoallelic variants in EP300 gene had cleft lip and palate.

DECIPHER database - Of 58 patients with heterozygous sequence variants in EP300, cleft palate, orofacial cleft and bifid uvula were found in one patient each.
Sources: Literature
Clefting v4.63 EP300 Achchuthan Shanmugasundram gene: EP300 was added
gene: EP300 was added to Clefting. Sources: Literature
Mode of inheritance for gene: EP300 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EP300 were set to 27648933; 37010288
Phenotypes for gene: EP300 were set to Rubinstein-Taybi syndrome 2, OMIM:613684
Review for gene: EP300 was set to RED
Added comment: This gene should be rated red as clefting has only been reported in a very small fraction of patients (<5%) identified with monoallleic variants in EP300.

PMID:27648933 - One of 52 patients with Rubinstein-Taybi syndrome caused by monoallelic variants in EP300 gene had cleft lip and palate.

DECIPHER database - Of 58 patients with heterozygous sequence variants in EP300, cleft palate, orofacial cleft and bifid uvula were found in one patient each.
Sources: Literature
Clefting v4.62 CHD3 Achchuthan Shanmugasundram changed review comment from: Of 28 patients with heterozygous sequence variants in CHD3 gene from DECIPHER database, one patient had cleft palate and another had submucous cleft hard palate.
Sources: Literature; to: Of 28 patients with heterozygous sequence variants in CHD3 gene from DECIPHER database, one patient had cleft palate and another had submucous cleft hard palate.
Sources: Literature
Clefting v4.62 CHD3 Achchuthan Shanmugasundram gene: CHD3 was added
gene: CHD3 was added to Clefting. Sources: Literature
Mode of inheritance for gene: CHD3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHD3 were set to 37010288
Phenotypes for gene: CHD3 were set to Snijders Blok-Campeau syndrome, OMIM:618205
Review for gene: CHD3 was set to RED
Added comment: Of 28 patients with heterozygous sequence variants in CHD3 gene from DECIPHER database, one patient had cleft palate and another had submucous cleft hard palate.
Sources: Literature
Clefting v4.61 AUTS2 Achchuthan Shanmugasundram Classified gene: AUTS2 as Amber List (moderate evidence)
Clefting v4.61 AUTS2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are five cases reported with cleft lip/ palate. However, clefting has only been reported in less than 10% of patients with monoalellic variants in AUTS2 from the DECIPHER database. Hence, this gene should be rated amber.
Clefting v4.61 AUTS2 Achchuthan Shanmugasundram Gene: auts2 has been classified as Amber List (Moderate Evidence).
Clefting v4.60 AUTS2 Achchuthan Shanmugasundram gene: AUTS2 was added
gene: AUTS2 was added to Clefting. Sources: Literature
Mode of inheritance for gene: AUTS2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AUTS2 were set to 31788251; 37010288
Phenotypes for gene: AUTS2 were set to Intellectual developmental disorder, autosomal dominant 26, OMIM:615834
Review for gene: AUTS2 was set to AMBER
Added comment: PMID:31788251 - A patient identified with a de novo heterozygous AUTS2 variant (c.1464_1467del ACTC/ p.Tyr488Ter) was reported with autism and cleft lip and palate.

DECIPHER database - Of 44 patients reported with heterozygous sequence variants, 4 patients had cleft lip or cleft palate (2 - cleft palate; 1 - cleft soft palate; 1 - unilateral cleft lip).
Sources: Literature
Clefting v4.59 ARID1A Achchuthan Shanmugasundram Phenotypes for gene: ARID1A were changed from to Coffin-Siris syndrome 2, OMIM:614607
Clefting v4.58 ARID1A Achchuthan Shanmugasundram edited their review of gene: ARID1A: Changed phenotypes to: Coffin-Siris syndrome 2, OMIM:614607
Clefting v4.58 ARID1A Achchuthan Shanmugasundram changed review comment from: Comment on list classification: Clefting is a minor feature on patients with monoallelic variants in ARID1A gene and it can be rated amber although there are three cases with clefting form a total of 34 cases.; to: Comment on list classification: Clefting is a minor feature on patients with monoallelic variants in ARID1A gene and it should be rated amber although there are three cases with clefting (from a total of 34 cases).
Clefting v4.58 ARID1A Achchuthan Shanmugasundram Classified gene: ARID1A as Amber List (moderate evidence)
Clefting v4.58 ARID1A Achchuthan Shanmugasundram Added comment: Comment on list classification: Clefting is a minor feature on patients with monoallelic variants in ARID1A gene and it can be rated amber although there are three cases with clefting form a total of 34 cases.
Clefting v4.58 ARID1A Achchuthan Shanmugasundram Gene: arid1a has been classified as Amber List (Moderate Evidence).
Clefting v4.57 ARID1A Achchuthan Shanmugasundram gene: ARID1A was added
gene: ARID1A was added to Clefting. Sources: Literature
Mode of inheritance for gene: ARID1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARID1A were set to 25168959; 37010288
Review for gene: ARID1A was set to AMBER
Added comment: PMID:25168959 - Two of eight patients with heterozygous variants in ARID1A gene had cleft palate.

DECIPHER database - One of 26 patients with heterozygous sequence variants in ARID1A gene had cleft palate.
Sources: Literature
Clefting v4.56 ADNP Achchuthan Shanmugasundram changed review comment from: PMID:29724491 - One child from a worldwide cohort of 78 individuals with variants in ADNP gene had submucous cleft palate.

DECIPHER database - Of 66 patients identified with heterozygous sequence variants in ADNP gene, one each (three in total) was reported with cleft soft palate, submucous cleft hard palate and submucous cleft lip.
Sources: Literature; to: Cleft lip/ palate has only been reported rarely in patients identified with monoallelic variants in ADNP gene.

PMID:29724491 - One child from a worldwide cohort of 78 individuals with variants in ADNP gene had submucous cleft palate.

DECIPHER database - Of 66 patients identified with heterozygous sequence variants in ADNP gene, one each (three in total) was reported with cleft soft palate, submucous cleft hard palate and submucous cleft lip.
Sources: Literature
Clefting v4.56 ADNP Achchuthan Shanmugasundram gene: ADNP was added
gene: ADNP was added to Clefting. Sources: Literature
Mode of inheritance for gene: ADNP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ADNP were set to 29724491; 37010288
Phenotypes for gene: ADNP were set to Helsmoortel-van der Aa syndrome, OMIM:615873
Review for gene: ADNP was set to RED
Added comment: PMID:29724491 - One child from a worldwide cohort of 78 individuals with variants in ADNP gene had submucous cleft palate.

DECIPHER database - Of 66 patients identified with heterozygous sequence variants in ADNP gene, one each (three in total) was reported with cleft soft palate, submucous cleft hard palate and submucous cleft lip.
Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v4.22 OTULIN Boaz Palterer reviewed gene: OTULIN: Rating: ; Mode of pathogenicity: None; Publications: 35587511; Phenotypes: life-threatening staphylococcal disease; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Dystonia, chorea or related movement disorder, childhood onset v3.17 DNAJC6 Sarah Leigh Tag Q3_23_promote_green tag was added to gene: DNAJC6.
Dystonia, chorea or related movement disorder, childhood onset v3.17 DNAJC6 Sarah Leigh Classified gene: DNAJC6 as Amber List (moderate evidence)
Dystonia, chorea or related movement disorder, childhood onset v3.17 DNAJC6 Sarah Leigh Gene: dnajc6 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.22 ARPC5 Boaz Palterer gene: ARPC5 was added
gene: ARPC5 was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: ARPC5 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ARPC5 were set to immunodeficiency; autoimmunity; inflammation; dysmorphisms; impaired wound healing; scoliosis; pneumatoceles; anemia
Penetrance for gene: ARPC5 were set to unknown
Review for gene: ARPC5 was set to GREEN
Added comment: Nunes-Santos et al. described 2 unrelated patients from 2 kindreds woith germline biallelic null mutations in ARPC5 presenting with a complex actinopathy phenotype of increased susceptibility to infections, autoimmunity, inflammation, and dysmorphisms.
There is strong biological rationale: ARPC5 is part of the Arp2/3 complex, related to WAS in Wiskott-Aldrich syndrome and ARPC1B deficiency. Strong functional ex vivo and in vitro data is presented.
( https://doi.org/10.1038/s41467-023-39272-0 )
Sources: Literature
Early onset or syndromic epilepsy v4.62 DNAJC6 Sarah Leigh Tag Q3_23_promote_green tag was added to gene: DNAJC6.
Early onset or syndromic epilepsy v4.62 DNAJC6 Sarah Leigh Classified gene: DNAJC6 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.62 DNAJC6 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Early onset or syndromic epilepsy v4.62 DNAJC6 Sarah Leigh Gene: dnajc6 has been classified as Amber List (Moderate Evidence).
Dystonia, chorea or related movement disorder, childhood onset v3.16 DNAJC6 Sarah Leigh Classified gene: DNAJC6 as Green List (high evidence)
Dystonia, chorea or related movement disorder, childhood onset v3.16 DNAJC6 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Dystonia, chorea or related movement disorder, childhood onset v3.16 DNAJC6 Sarah Leigh Gene: dnajc6 has been classified as Green List (High Evidence).
Dystonia, chorea or related movement disorder, adult onset v3.4 DNAJC6 Sarah Leigh Publications for gene: DNAJC6 were set to 26528954; 23211418; 27687717; 26703368; 22563501
Neurodegenerative disorders, adult onset v4.28 DNAJC6 Sarah Leigh Publications for gene: DNAJC6 were set to 23211418; 27687717; 26528954; 22563501; 26703368
Parkinson Disease and Complex Parkinsonism v1.116 DNAJC6 Sarah Leigh Publications for gene: DNAJC6 were set to 26528954; 27687717; 26703368; 22563501; 23211418
Dystonia, chorea or related movement disorder, childhood onset v3.15 DNAJC6 Sarah Leigh Publications for gene: DNAJC6 were set to 34175496
Dystonia, chorea or related movement disorder, childhood onset v3.14 DNAJC6 Sarah Leigh Phenotypes for gene: DNAJC6 were changed from to Parkinson disease 19b, early-onset, OMIM:615528; Parkinson disease 19a juvenile-onset, OMIM:615528; juvenile onset Parkinson disease 19A, MONDO:0014231
Dystonia, chorea or related movement disorder, childhood onset v3.13 DNAJC6 Sarah Leigh reviewed gene: DNAJC6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Early onset or syndromic epilepsy v4.61 DNAJC6 Sarah Leigh edited their review of gene: DNAJC6: Added comment: DNAJC6 variants are associated with Parkinson disease 19b, early-onset (OMIM:615528), but not with a phenotype in Gen2Phen. At least nine variants have been reported in unrelated families. Seizures were reported in 5/9 families and dystonia was reported in 4/9 families reported (data review in PMID: 34175496.; Changed rating: GREEN
Primary immunodeficiency or monogenic inflammatory bowel disease v4.22 DOCK11 Boaz Palterer gene: DOCK11 was added
gene: DOCK11 was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: DOCK11 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: DOCK11 were set to 36952639
Phenotypes for gene: DOCK11 were set to early-onset autoimmunity; cytopenia; systemic lupus erythematosus; dermatitis; enteropathy
Penetrance for gene: DOCK11 were set to unknown
Review for gene: DOCK11 was set to GREEN
Added comment: Boussard et al. described 8 male patients, from 7 unrelated families, with hemizygous DOCK11 missense variants leading to reduced DOCK11 expression. The patients presented with early-onset autoimmunity, including cytopenia, systemic lupus erythematosus, skin, and digestive manifestations. Extensive ex vivo and in vitro functional validation.
Sources: Literature
Clefting v4.55 ZC4H2 Achchuthan Shanmugasundram changed review comment from: PMID:31206972 - Of 42 families identified with variants in de novo and inherited heterozygous variants in ZC4H2 gene, eight patients had cleft palate in addition to several other clinical presentations. These included one patient with cleft palate from the DDD study (DECIPHER database)

DECIPHER database - Of 13 patients with monoallelic sequence variants, three patients had cleft palate.

Cleft palate has been recorded as one of the clinical presentations of female-restricted Wieacker-Wolff syndrome (MIM #301041) in OMIM.
Sources: Literature; to: PMID:31206972 - Of 42 families identified with de novo and inherited variants in ZC4H2 gene, eight patients had cleft palate in addition to several other clinical presentations. These included one patient with cleft palate from the DDD study (DECIPHER database)

DECIPHER database - Of 13 patients with sequence variants, three patients had cleft palate.

Cleft palate has been recorded as one of the clinical presentations of female-restricted Wieacker-Wolff syndrome (MIM #301041) in OMIM.
Sources: Literature
Clefting v4.55 ZC4H2 Achchuthan Shanmugasundram Mode of inheritance for gene: ZC4H2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Clefting v4.54 ZC4H2 Achchuthan Shanmugasundram edited their review of gene: ZC4H2: Changed mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Clefting v4.54 ZC4H2 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There are ten patients reported with cleft palate. Hence, this gene can be promoted to green rating in the next GMS update.; to: Comment on list classification: There are ten unrelated patients reported with cleft palate. Hence, this gene can be promoted to green rating in the next GMS update.
Clefting v4.54 ZC4H2 Achchuthan Shanmugasundram changed review comment from: PMID:31206972 - Of 42 families identified with variants in de novo and inherited heterozygous variants in ZC4H2 gene, eight patients were had cleft palate in addition to several other clinical presentations. These included one patient with cleft palate from the DDD study (DECIPHER database)

DECIPHER database - Of 13 patients with monoallelic sequence variants, three patients had cleft palate.

Cleft palate has been recorded as one of the clinical presentations of female-restricted Wieacker-Wolff syndrome (MIM #301041) in OMIM.
Sources: Literature; to: PMID:31206972 - Of 42 families identified with variants in de novo and inherited heterozygous variants in ZC4H2 gene, eight patients had cleft palate in addition to several other clinical presentations. These included one patient with cleft palate from the DDD study (DECIPHER database)

DECIPHER database - Of 13 patients with monoallelic sequence variants, three patients had cleft palate.

Cleft palate has been recorded as one of the clinical presentations of female-restricted Wieacker-Wolff syndrome (MIM #301041) in OMIM.
Sources: Literature
Dystonia, chorea or related movement disorder, adult onset v3.3 DNAJC6 Sarah Leigh Phenotypes for gene: DNAJC6 were changed from Parkinson disease 19, juvenile-onset, OMIM:615528; Parkinson disease 19b, early-onset, OMIM:615528 to Parkinson disease 19b, early-onset, OMIM:615528; Parkinson disease 19a juvenile-onset, OMIM:615528; juvenile onset Parkinson disease 19A, MONDO:0014231
Neurodegenerative disorders, adult onset v4.27 DNAJC6 Sarah Leigh Phenotypes for gene: DNAJC6 were changed from Parkinson disease 19b, early-onset, OMIM:615528; Parkinson disease 19a, juvenile-onset, OMIM:615528 to Parkinson disease 19b, early-onset, OMIM:615528; Parkinson disease 19a juvenile-onset, OMIM:615528; juvenile onset Parkinson disease 19A, MONDO:0014231
Parkinson Disease and Complex Parkinsonism v1.115 DNAJC6 Sarah Leigh Phenotypes for gene: DNAJC6 were changed from Parkinson disease 19, juvenile-onset, 615528; Parkinson disease 19a, juvenile-onset; Parkinson disease 19b, early-onset to Parkinson disease 19b, early-onset, OMIM:615528; Parkinson disease 19a juvenile-onset, OMIM:615528; juvenile onset Parkinson disease 19A, MONDO:0014231
Early onset or syndromic epilepsy v4.61 DNAJC6 Sarah Leigh Deleted their comment
Early onset or syndromic epilepsy v4.61 DNAJC6 Sarah Leigh Phenotypes for gene: DNAJC6 were changed from Parkinson disease 19b, early-onset, OMIM:615528; juvenile onset Parkinson disease 19A, MONDO:0014231 to Parkinson disease 19b, early-onset, OMIM:615528; Parkinson disease 19a juvenile-onset, OMIM:615528; juvenile onset Parkinson disease 19A, MONDO:0014231
Early onset or syndromic epilepsy v4.60 DNAJC6 Sarah Leigh Mode of inheritance for gene: DNAJC6 was changed from to BIALLELIC, autosomal or pseudoautosomal
Clefting v4.54 ZC4H2 Achchuthan Shanmugasundram changed review comment from: PMID:31206972 - Of 42 families identified with variants in de novo and inherited heterozygous variants in ZC4H2 gene, eight patients were had cleft palate in addition to several other clinical presentations. These included one patient with cleft palate from the DDD study (DECIPHER database)

DECIPHER database - Of 13 patients with monoallelic sequence variants, three patients had cleft palate.
Sources: Literature; to: PMID:31206972 - Of 42 families identified with variants in de novo and inherited heterozygous variants in ZC4H2 gene, eight patients were had cleft palate in addition to several other clinical presentations. These included one patient with cleft palate from the DDD study (DECIPHER database)

DECIPHER database - Of 13 patients with monoallelic sequence variants, three patients had cleft palate.

Cleft palate has been recorded as one of the clinical presentations of female-restricted Wieacker-Wolff syndrome (MIM #301041) in OMIM.
Sources: Literature
Clefting v4.54 ZC4H2 Achchuthan Shanmugasundram Classified gene: ZC4H2 as Amber List (moderate evidence)
Clefting v4.54 ZC4H2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are ten patients reported with cleft palate. Hence, this gene can be promoted to green rating in the next GMS update.
Clefting v4.54 ZC4H2 Achchuthan Shanmugasundram Gene: zc4h2 has been classified as Amber List (Moderate Evidence).
Clefting v4.53 ZC4H2 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: ZC4H2.
Clefting v4.53 ZC4H2 Achchuthan Shanmugasundram gene: ZC4H2 was added
gene: ZC4H2 was added to Clefting. Sources: Literature
Mode of inheritance for gene: ZC4H2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZC4H2 were set to 31206972; 37010288
Phenotypes for gene: ZC4H2 were set to Wieacker-Wolff syndrome, female-restricted, OMIM:301041
Review for gene: ZC4H2 was set to GREEN
Added comment: PMID:31206972 - Of 42 families identified with variants in de novo and inherited heterozygous variants in ZC4H2 gene, eight patients were had cleft palate in addition to several other clinical presentations. These included one patient with cleft palate from the DDD study (DECIPHER database)

DECIPHER database - Of 13 patients with monoallelic sequence variants, three patients had cleft palate.
Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v4.22 SRP72 Lauma Freimane gene: SRP72 was added
gene: SRP72 was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature,Research
Mode of inheritance for gene: SRP72 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SRP72 were set to 32098966
Phenotypes for gene: SRP72 were set to Familial MDS/AML; inherited bone marrow failure syndromes (IBMFS); congenital neutropenia; Shwachman-Diamond syndrome
Early onset or syndromic epilepsy v4.59 DNAJC6 Sarah Leigh Publications for gene: DNAJC6 were set to 22563501; 23211418; 26528954; 34175496; 26703368
Early onset or syndromic epilepsy v4.58 DNAJC6 Sarah Leigh Publications for gene: DNAJC6 were set to 23211418; 34175496
Early onset or syndromic epilepsy v4.57 DNAJC6 Sarah Leigh Publications for gene: DNAJC6 were set to
Early onset or syndromic epilepsy v4.56 DNAJC6 Sarah Leigh Added comment: Comment on phenotypes: OMIM:615528 also includes Parkinson disease 19a, juvenile-onset
Early onset or syndromic epilepsy v4.56 DNAJC6 Sarah Leigh Phenotypes for gene: DNAJC6 were changed from to Parkinson disease 19b, early-onset, OMIM:615528; juvenile onset Parkinson disease 19A, MONDO:0014231
Early onset or syndromic epilepsy v4.55 SAMD12 Sarah Leigh reviewed gene: SAMD12: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Clefting v4.52 TRRAP Achchuthan Shanmugasundram changed review comment from: PMID:30827496 - Out of 13 unrelated individuals with a complex syndromic neurodevelopmental disorder comprising global developmental delay and intellectual disability and identified with monoallelic variants in TRRAP gene, five had cleft lip and palate.

DECIPHER database - Out of 18 patients with heterozygous sequence variants in TRRAP gene, two were reported with cleft lip and palate.
Sources: Literature; to: PMID:30827496 - Out of 13 unrelated individuals with a complex syndromic neurodevelopmental disorder comprising global developmental delay and intellectual disability and identified with monoallelic variants in TRRAP gene, five had cleft lip and palate.

DECIPHER database - Out of 18 patients with heterozygous sequence variants in TRRAP gene, two were reported with cleft lip and palate.

OMIM has also recorded cleft lip and palate as clinical presentations of the syndrome associated with dominant variants in TRRAP (MIM #618454).
Sources: Literature
Clefting v4.52 TRRAP Achchuthan Shanmugasundram Deleted their comment
Clefting v4.52 TRRAP Achchuthan Shanmugasundram Classified gene: TRRAP as Amber List (moderate evidence)
Clefting v4.52 TRRAP Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (7 unrelated cases) for this gene to be promoted to green rating at the next major update.
Clefting v4.52 TRRAP Achchuthan Shanmugasundram Gene: trrap has been classified as Amber List (Moderate Evidence).
Clefting v4.52 TRRAP Achchuthan Shanmugasundram Classified gene: TRRAP as Amber List (moderate evidence)
Clefting v4.52 TRRAP Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (7 unrelated cases) for this gene to be promoted green rating at the next major update.
Clefting v4.52 TRRAP Achchuthan Shanmugasundram Gene: trrap has been classified as Amber List (Moderate Evidence).
Clefting v4.51 TRRAP Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: TRRAP.
Clefting v4.51 TRRAP Achchuthan Shanmugasundram gene: TRRAP was added
gene: TRRAP was added to Clefting. Sources: Literature
Mode of inheritance for gene: TRRAP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRRAP were set to 30827496; 37010288
Phenotypes for gene: TRRAP were set to Developmental delay with or without dysmorphic facies and autism, OMIM:618454
Review for gene: TRRAP was set to GREEN
Added comment: PMID:30827496 - Out of 13 unrelated individuals with a complex syndromic neurodevelopmental disorder comprising global developmental delay and intellectual disability and identified with monoallelic variants in TRRAP gene, five had cleft lip and palate.

DECIPHER database - Out of 18 patients with heterozygous sequence variants in TRRAP gene, two were reported with cleft lip and palate.
Sources: Literature
Early onset or syndromic epilepsy v4.55 SAMD12 Sarah Leigh Phenotypes for gene: SAMD12 were changed from Epilepsy, familial adult myoclonic, 1, MIM# 601068 to Epilepsy, familial adult myoclonic, 1, OMIM:601068; epilepsy, familial adult myoclonic, 1, MONDO:0010985
Clefting v4.50 TRAF7 Achchuthan Shanmugasundram Classified gene: TRAF7 as Amber List (moderate evidence)
Clefting v4.50 TRAF7 Achchuthan Shanmugasundram Gene: traf7 has been classified as Amber List (Moderate Evidence).
Clefting v4.49 TRAF7 Achchuthan Shanmugasundram Publications for gene: TRAF7 were set to 32376980; 37010288
Clefting v4.49 TRAF7 Achchuthan Shanmugasundram Publications for gene: TRAF7 were set to 32376980
Clefting v4.48 TRAF7 Achchuthan Shanmugasundram edited their review of gene: TRAF7: Changed publications to: 32376980, 37010288
Clefting v4.48 TRAF7 Achchuthan Shanmugasundram gene: TRAF7 was added
gene: TRAF7 was added to Clefting. Sources: Literature
Mode of inheritance for gene: TRAF7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRAF7 were set to 32376980
Phenotypes for gene: TRAF7 were set to Cardiac, facial, and digital anomalies with developmental delay, OMIM:618164
Review for gene: TRAF7 was set to AMBER
Added comment: PMID:32376980 - 45 patients were identified with heterozygous variants in TRAF7 gene, of which one patient had cleft palate and three patients had submucous cleft palate.

DECIPHER database - One of 15 patients with heterozygous sequence variants in TRAF7 gene had cleft palate as one of the clinical presentations.
Sources: Literature
Early onset or syndromic epilepsy v4.54 SAMD12 Sarah Leigh Publications for gene: SAMD12 were set to 30194086; 29507423
Early onset or syndromic epilepsy v4.53 SAMD12 Sarah Leigh Classified gene: SAMD12 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.53 SAMD12 Sarah Leigh Gene: samd12 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.52 SAMD12 Sarah Leigh Tag STR tag was added to gene: SAMD12.
Clefting v4.47 STAG2 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There are ten cases identified with cleft lip/ palate, cleft soft palate or submucous cleft soft palate. Hence, this gene can be promoted to green rating at the next GMS review.; to: Comment on list classification: There are eight unrelated cases identified with cleft lip/ palate and two cases were identified with cleft soft palate or submucous cleft soft palate. Hence, this gene should be promoted to green rating at the next GMS review.
Clefting v4.47 STAG2 Achchuthan Shanmugasundram Classified gene: STAG2 as Amber List (moderate evidence)
Clefting v4.47 STAG2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are ten cases identified with cleft lip/ palate, cleft soft palate or submucous cleft soft palate. Hence, this gene can be promoted to green rating at the next GMS review.
Clefting v4.47 STAG2 Achchuthan Shanmugasundram Gene: stag2 has been classified as Amber List (Moderate Evidence).
Clefting v4.46 STAG2 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: STAG2.
Clefting v4.46 STAG2 Achchuthan Shanmugasundram gene: STAG2 was added
gene: STAG2 was added to Clefting. Sources: Literature
Mode of inheritance for gene: STAG2 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: STAG2 were set to 28296084; 29263825; 30158690; 31334757; 33014403; 37010288
Phenotypes for gene: STAG2 were set to Holoprosencephaly 13, X-linked, OMIM:301043; Mullegama-Klein-Martinez syndrome, OMIM:301022
Review for gene: STAG2 was set to GREEN
Added comment: PMID:33014403 - Two female patients identified with de novo variants in STAG2. One had cleft lip/ palate and other had cleft palate. In addition, five additional cases with cleft lip/ palate were also reported from literature review in this publication.

DECIPHER database - Of ten patients with sequence variants in STAG2 gene, one each was identified with cleft palate, cleft soft palate and submucous cleft soft palate (PMID:37010288).
Sources: Literature
Clefting v4.45 SMARCA4 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: SMARCA4.
Clefting v4.45 SMARCA4 Achchuthan Shanmugasundram Deleted their comment
Clefting v4.45 SMARCA4 Achchuthan Shanmugasundram Classified gene: SMARCA4 as Amber List (moderate evidence)
Clefting v4.45 SMARCA4 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are five unrelated cases with cleft plate and one case each with submucous cleft palate and bifid uvula. This gene can be promoted to green rating in the next GMS review.
Clefting v4.45 SMARCA4 Achchuthan Shanmugasundram Gene: smarca4 has been classified as Amber List (Moderate Evidence).
Clefting v4.44 SMARCA4 Achchuthan Shanmugasundram Classified gene: SMARCA4 as Amber List (moderate evidence)
Clefting v4.44 SMARCA4 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are five unrelated cases with cleft plate and one case each with submucous cleft palate and bifid uvula. This gene can be promoted to green rating in the next GMS review.
Clefting v4.44 SMARCA4 Achchuthan Shanmugasundram Gene: smarca4 has been classified as Amber List (Moderate Evidence).
Clefting v4.43 SMARCA4 Achchuthan Shanmugasundram gene: SMARCA4 was added
gene: SMARCA4 was added to Clefting. Sources: Literature
Mode of inheritance for gene: SMARCA4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMARCA4 were set to 25168959; 37010288
Phenotypes for gene: SMARCA4 were set to Coffin-Siris syndrome 4, OMIM:614609
Review for gene: SMARCA4 was set to GREEN
Added comment: PMID:25168959 - 4 of 12 patients with variants in SMARCA4 had cleft palate and another patient had submucous cleft palate.

DECIPHER database - One of 22 patients with heterozygous sequence variants had cleft palate and another patient had bifid uvula (PMID:37010288)
Sources: Literature
Intellectual disability v5.191 MKL2 Dmitrijs Rots gene: MKL2 was added
gene: MKL2 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: MKL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MKL2 were set to PMID:37013900
Phenotypes for gene: MKL2 were set to neurodevelopmental phenotype with dysmorphic features
Mode of pathogenicity for gene: MKL2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: MKL2 was set to GREEN
Added comment: 2 cases with de novo missense GoF variants in MRTFB (previously known as MKL2) + functional evidence
Sources: Literature
Clefting v4.42 POGZ Achchuthan Shanmugasundram Classified gene: POGZ as Amber List (moderate evidence)
Clefting v4.42 POGZ Achchuthan Shanmugasundram Added comment: Comment on list classification: Although there are more than three unrelated cases reported with either cleft palate or bifid uvula in total, this phenotype is not consistently present in patients with monoallelic variants in POGZ gene. Hence, this gene should only be rated amber.
Clefting v4.42 POGZ Achchuthan Shanmugasundram Gene: pogz has been classified as Amber List (Moderate Evidence).
Clefting v4.41 POGZ Achchuthan Shanmugasundram Publications for gene: POGZ were set to 26739615; 31782611
Clefting v4.40 POGZ Achchuthan Shanmugasundram changed review comment from: PMID:26739615 - Five unrelated individuals were identified with de novo truncating variants in POGZ gene, of which one individual had cleft palate and another one had bifid uvula.

PMID:31782611 - In this cohort of 22 individuals with 21 different loss of function variants in POGZ, two patients were reported with bifid uvula.

DECIPHER database - Of 42 patients with heterozygous sequence variants, one had cleft palate and another one had bifid uvula.

The OMIM entry for White-Sutton syndrome (MIM #616364) does not currently include cleft lip/ palate as one of the clinical manifestations of this syndrome.
Sources: Literature; to: PMID:26739615 - Five unrelated individuals were identified with de novo truncating variants in POGZ gene, of which one individual had cleft palate and another one had bifid uvula.

PMID:31782611 - In this cohort of 22 individuals with 21 different loss of function variants in POGZ, two patients were reported with bifid uvula.

DECIPHER database - Of 42 patients with heterozygous sequence variants, one had cleft palate and another one had bifid uvula (PMID:37010288).

The OMIM entry for White-Sutton syndrome (MIM #616364) does not currently include cleft lip/ palate as one of the clinical manifestations of this syndrome.
Sources: Literature
Clefting v4.40 POGZ Achchuthan Shanmugasundram edited their review of gene: POGZ: Changed publications to: 26739615, 31782611, 37010288
Clefting v4.40 POGZ Achchuthan Shanmugasundram gene: POGZ was added
gene: POGZ was added to Clefting. Sources: Literature
Mode of inheritance for gene: POGZ was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POGZ were set to 26739615; 31782611
Phenotypes for gene: POGZ were set to White-Sutton syndrome, OMIM:616364
Review for gene: POGZ was set to AMBER
Added comment: PMID:26739615 - Five unrelated individuals were identified with de novo truncating variants in POGZ gene, of which one individual had cleft palate and another one had bifid uvula.

PMID:31782611 - In this cohort of 22 individuals with 21 different loss of function variants in POGZ, two patients were reported with bifid uvula.

DECIPHER database - Of 42 patients with heterozygous sequence variants, one had cleft palate and another one had bifid uvula.

The OMIM entry for White-Sutton syndrome (MIM #616364) does not currently include cleft lip/ palate as one of the clinical manifestations of this syndrome.
Sources: Literature
Hereditary neuropathy or pain disorder v3.35 ITPR3 Sarah Leigh Classified gene: ITPR3 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v3.35 ITPR3 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Hereditary neuropathy or pain disorder v3.35 ITPR3 Sarah Leigh Gene: itpr3 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v3.34 ITPR3 Sarah Leigh Tag Q3_23_promote_green tag was added to gene: ITPR3.
Hereditary neuropathy or pain disorder v3.34 ITPR3 Sarah Leigh reviewed gene: ITPR3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v3.34 ITPR3 Sarah Leigh Phenotypes for gene: ITPR3 were changed from Charcot-Marie-Tooth disease to Charcot-Marie-Tooth disease, demyelinating, type 1J, OMIM:620111
Hereditary neuropathy or pain disorder v3.33 ITPR3 Sarah Leigh Publications for gene: ITPR3 were set to 32949214
Hereditary neuropathy or pain disorder v3.32 ITPR3 Sarah Leigh Classified gene: ITPR3 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v3.32 ITPR3 Sarah Leigh Gene: itpr3 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.52 EIF4A2 Sarah Leigh Classified gene: EIF4A2 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.52 EIF4A2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rating Green at the major review.
Early onset or syndromic epilepsy v4.52 EIF4A2 Sarah Leigh Gene: eif4a2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.191 EIF4A2 Sarah Leigh Classified gene: EIF4A2 as Amber List (moderate evidence)
Intellectual disability v5.191 EIF4A2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rating Green at the major review.
Intellectual disability v5.191 EIF4A2 Sarah Leigh Gene: eif4a2 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.51 EIF4A2 Sarah Leigh gene: EIF4A2 was added
gene: EIF4A2 was added to Early onset or syndromic epilepsy. Sources: Literature
Q3_23_promote_green tags were added to gene: EIF4A2.
Mode of inheritance for gene: EIF4A2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: EIF4A2 were set to 36528028
Phenotypes for gene: EIF4A2 were set to Neurodevelopmental disorder
Review for gene: EIF4A2 was set to GREEN
Added comment: EIF4A2 has not been associated with a phenotype in OMIM, Gen2Phen or Mondo at the time of reporting. PMID: 36528028 reports the findings of an international collaboration through Matchmaker Exchange, where EIF4A2 variants are found in cases with neurodevelopmental disorder characterized by intellectual disability, hypotonia, and epilepsy. A total of 15 EIF4A2 variants have been reported in PMID: 36528028, with 12 variants occurring as de novo monoallelic in 12 individuals and 3 as biallelic in two unrelated cases (one as homozygote and the other as compound heterozygous). Severe intellectual was seen in 6/10 unrelated cases where an assessment was made, epilepsy was evident in 10/14 unrelated cases and 13/14 cases had hyptonia. Functional studies were also presented and it would appear that both loss and gain functions maybe associated with EIF4A2 variants.
Sources: Literature
Intellectual disability v5.190 EIF4A2 Sarah Leigh gene: EIF4A2 was added
gene: EIF4A2 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Q3_23_promote_green tags were added to gene: EIF4A2.
Mode of inheritance for gene: EIF4A2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: EIF4A2 were set to 36528028
Phenotypes for gene: EIF4A2 were set to Neurodevelopmental disorder
Review for gene: EIF4A2 was set to GREEN
Added comment: EIF4A2 has not been associated with a phenotype in OMIM, Gen2Phen or Mondo at the time of reporting. PMID: 36528028 reports the findings of an international collaboration through Matchmaker Exchange, where EIF4A2 variants are found in cases with neurodevelopmental disorder characterized by intellectual disability, hypotonia, and epilepsy. A total of 15 EIF4A2 variants have been reported in PMID: 36528028, with 12 variants occurring as de novo monoallelic in 12 individuals and 3 as biallelic in two unrelated cases (one as homozygote and the other as compound heterozygous). Severe intellectual was seen in 6/10 unrelated cases where an assessment was made, epilepsy was evident in 10/14 unrelated cases and 13/14 cases had hyptonia. Functional studies were also presented and it would appear that both loss and gain functions maybe associated with EIF4A2 variants.
Sources: Literature
Clefting v4.39 PGM1 Achchuthan Shanmugasundram Classified gene: PGM1 as Amber List (moderate evidence)
Clefting v4.39 PGM1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (>10 unrelated cases) for this gene to be rated green at the next GMS review.
Clefting v4.39 PGM1 Achchuthan Shanmugasundram Gene: pgm1 has been classified as Amber List (Moderate Evidence).
Clefting v4.38 PGM1 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: PGM1.
Clefting v4.38 PGM1 Achchuthan Shanmugasundram Phenotypes for gene: PGM1 were changed from Cleft palate to Congenital disorder of glycosylation, type It, OMIM:14921
Clefting v4.37 PGM1 Achchuthan Shanmugasundram Publications for gene: PGM1 were set to 24499211; 37010288
Clefting v4.37 PGM1 Achchuthan Shanmugasundram Publications for gene: PGM1 were set to
Clefting v4.36 PGM1 Achchuthan Shanmugasundram Mode of inheritance for gene: PGM1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Clefting v4.35 PGM1 Achchuthan Shanmugasundram changed review comment from: PMID:24499211 - 19 patients from 16 families with biallelic variants in PGM1 and presenting with CGG1T. Of these, 16 patients from 13 different families had cleft palate and/ or bifid uvula.

DECIPHER database - Only one patient reported with compound heterozygous variant in PGM1 gene and this patient had cleft palate (PMID:37010288); to: PMID:24499211 - 19 patients from 16 families with biallelic variants in PGM1 and presenting with CGG1T. Of these, 16 patients from 13 different families had cleft palate and/ or bifid uvula.

DECIPHER database - Only one patient reported with compound heterozygous variant in PGM1 gene and this patient had cleft palate (PMID:37010288)

OMIM associated autosomal recessive PGM1 variants to congenital disorder of glycosylation, type It (MIM #14921) and cleft palate and bifid uvula have been recorded as clinical presentations of this disorder.
Clefting v4.35 PGM1 Achchuthan Shanmugasundram reviewed gene: PGM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24499211, 37010288; Phenotypes: Congenital disorder of glycosylation, type It, OMIM:14921; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Clefting v4.35 PGAP3 Achchuthan Shanmugasundram Classified gene: PGAP3 as Amber List (moderate evidence)
Clefting v4.35 PGAP3 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (>10 unrelated cases) available for promoting this gene to green rating in the next GMS review.
Clefting v4.35 PGAP3 Achchuthan Shanmugasundram Gene: pgap3 has been classified as Amber List (Moderate Evidence).
Clefting v4.34 PGAP3 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: PGAP3.
Clefting v4.34 PGAP3 Achchuthan Shanmugasundram gene: PGAP3 was added
gene: PGAP3 was added to Clefting. Sources: Literature
Mode of inheritance for gene: PGAP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PGAP3 were set to 28390064; 37010288
Phenotypes for gene: PGAP3 were set to Hyperphosphatasia with impaired intellectual development syndrome 4, OMIM:615716
Review for gene: PGAP3 was set to GREEN
Added comment: PMID:28390064 - 10 patients from eight families presented with developmental delay, severe intellectual disability, distinct facial dysmorphism and increased alkaline phosphatase. Nine patients from seven families were homozygous for the same variant (c.402dupC/ p.M135Hfs*28), while one patient had a different homozygous variant ( c.817_820delGACT/ p.D273Sfs*37). Of nine patients with p.M135Hfs*28 variant, eight patients from seven families (except one of the two patients from family 7) had cleft palate. But, the only patient with the different variant did not have cleft palate.

DECIPHER database - Of seven patients reported with biallelic sequence variants, three patents with homozygous variants were reported with cleft palate and two patients with compound heterozygous variants were reported with cleft soft palate (PMID:37010288).

OMIM associated patients with autosomal recessive variants in PGAP3 to hyperphosphatasia with impaired intellectual development syndrome 4 (MIM #615716) and cleft palate has been recorded as one of the clinical manifestations occurring in some patients.
Sources: Literature
Clefting v4.33 MED13L Achchuthan Shanmugasundram changed review comment from: PMID:25137640 - Cleft palate was present in the patient reported with intellectual disability and dysmorphic facial features.
PMID:25712080 - Cleft palate was reported in a single case (patient 1) of MED13L haploinsufficiency.
PMID:29159987 - One of the two patients reported with de novo variants had repaired posterior cleft palate and the other had only high palate.
PMID:29511999 - One of 36 patients with monoallelic variants had posterior cleft palate.
DECIPHER database - Of 72 patients reported with heterozygous sequence variants, cleft palate was reported in two patients, cleft soft palate in one and submucous cleft hard palate in one patient (PMID:37010288).; to: Although there are more than three cases reported with clefting, this feature is not consistently found in patients with monoallelic variants in MED13L gene.

PMID:25137640 - Cleft palate was present in the patient reported with intellectual disability and dysmorphic facial features.
PMID:25712080 - Cleft palate was reported in a single case (patient 1) of MED13L haploinsufficiency.
PMID:29159987 - One of the two patients reported with de novo variants had repaired posterior cleft palate and the other had only high palate.
PMID:29511999 - One of 36 patients with monoallelic variants had posterior cleft palate.
DECIPHER database - Of 72 patients reported with heterozygous sequence variants, cleft palate was reported in two patients, cleft soft palate in one and submucous cleft hard palate in one patient (PMID:37010288).
Clefting v4.33 MED13L Achchuthan Shanmugasundram Publications for gene: MED13L were set to 25137640; 25712080; 29159987; 29511999; 37010288
Clefting v4.33 MED13L Achchuthan Shanmugasundram Publications for gene: MED13L were set to 25137640; 25712080; 29159987; 29511999; 37010288
Clefting v4.33 MED13L Achchuthan Shanmugasundram Publications for gene: MED13L were set to 25137640; 25712080
Clefting v4.32 MED13L Achchuthan Shanmugasundram changed review comment from: PMID:25137640 - Cleft palate was present in the patient reported with intellectual disability and dysmorphic facial features.
PMID:25712080 - Cleft palate was reported in a single case (patient 1) of MED13L haploinsufficiency.
PMID:29159987 - One of the two patients reported with de novo variants had repaired posterior cleft palate and the other had only high palate.
PMID:29511999 - One of 36 patients with monoallelic variants had posterior cleft palate.
DECIPHER database - Of 72 patients reported with heterozygous sequence variants, cleft palate was reported in two patients, cleft soft palate in one and submucous cleft hard palate in one patient.; to: PMID:25137640 - Cleft palate was present in the patient reported with intellectual disability and dysmorphic facial features.
PMID:25712080 - Cleft palate was reported in a single case (patient 1) of MED13L haploinsufficiency.
PMID:29159987 - One of the two patients reported with de novo variants had repaired posterior cleft palate and the other had only high palate.
PMID:29511999 - One of 36 patients with monoallelic variants had posterior cleft palate.
DECIPHER database - Of 72 patients reported with heterozygous sequence variants, cleft palate was reported in two patients, cleft soft palate in one and submucous cleft hard palate in one patient (PMID:37010288).
Clefting v4.32 MED13L Achchuthan Shanmugasundram edited their review of gene: MED13L: Changed publications to: 25137640, 25712080, 29159987, 29511999, 37010288
Clefting v4.32 MED13L Achchuthan Shanmugasundram reviewed gene: MED13L: Rating: AMBER; Mode of pathogenicity: None; Publications: 25712080, 29159987, 29511999; Phenotypes: Impaired intellectual development and distinctive facial features with or without cardiac defects, OMIM:616789; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Clefting v4.32 KMT2A Achchuthan Shanmugasundram Classified gene: KMT2A as Amber List (moderate evidence)
Clefting v4.32 KMT2A Achchuthan Shanmugasundram Added comment: Comment on list classification: Although there are more than three cases reported with clefting, it is only present in a very small subsection of patients with KMT2A monoallelic variants. Hence, this gene can only be rated amber with current evidence.
Clefting v4.32 KMT2A Achchuthan Shanmugasundram Gene: kmt2a has been classified as Amber List (Moderate Evidence).
Clefting v4.31 KMT2A Achchuthan Shanmugasundram gene: KMT2A was added
gene: KMT2A was added to Clefting. Sources: Literature
Mode of inheritance for gene: KMT2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KMT2A were set to 25929198; 30305169; 31710778; 37010288
Phenotypes for gene: KMT2A were set to Wiedemann-Steiner syndrome, OMIM:605130
Review for gene: KMT2A was set to AMBER
Added comment: PMID:25929198 - De novo KMT2A variant (p.Arg1083Ter) in monozygotic twins and they had submucosal cleft palate.

PMID:30305169 - Two of 14 patients with KMT2A variants and presenting with Wiedemann–Steiner syndrome had cleft palate.

PMID:31710778 - Both patients reported with KMT2A variants had only high arched palate and not cleft palate.

DECIPHER database - None of the reported patients had cleft lip/ palate and only one of 115 had bifid uvula (PMID:37010288)
Sources: Literature
Clefting v4.30 KAT6B Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: KAT6B.
Clefting v4.30 KAT6B Achchuthan Shanmugasundram Deleted their comment
Clefting v4.30 KAT6B Achchuthan Shanmugasundram Deleted their comment
Clefting v4.30 KAT6B Achchuthan Shanmugasundram Classified gene: KAT6B as Amber List (moderate evidence)
Clefting v4.30 KAT6B Achchuthan Shanmugasundram Added comment: Comment on list classification: Although clefting is a minor feature in patients reported with monoallelic KAT6B variants, it has been reported in more than 20 cases so far. Hence, this gene should be promoted to green rating in the next GMS review.
Clefting v4.30 KAT6B Achchuthan Shanmugasundram Gene: kat6b has been classified as Amber List (Moderate Evidence).
Clefting v4.29 KAT6B Achchuthan Shanmugasundram Classified gene: KAT6B as Amber List (moderate evidence)
Clefting v4.29 KAT6B Achchuthan Shanmugasundram Added comment: Comment on list classification: Although clefting is a minor feature in patients reported with monoallelic KAT6B variants, it has been reported in more than 20 cases so far. Hence, this gene should be promoted to green rating in the next GMS review.
Clefting v4.29 KAT6B Achchuthan Shanmugasundram Gene: kat6b has been classified as Amber List (Moderate Evidence).
Clefting v4.29 KAT6B Achchuthan Shanmugasundram Classified gene: KAT6B as Amber List (moderate evidence)
Clefting v4.29 KAT6B Achchuthan Shanmugasundram Added comment: Comment on list classification: Although clefting is a minor feature in patients reported with monoallelic KAT6B variants, it has been reported in more than 20 cases so far. Hence, this gene should be promoted to green rating in the next GMS review.
Clefting v4.29 KAT6B Achchuthan Shanmugasundram Gene: kat6b has been classified as Amber List (Moderate Evidence).
Clefting v4.28 GLI2 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: Although cleating is a minor feature in patients reported with monoallelic GLI2 variants, it has been reported in more than 15 cases. Hence, this gene should be promoted to green rating in the next GMS review.; to: Comment on list classification: Although clefting is a minor feature in patients reported with monoallelic GLI2 variants, it has been reported in more than 15 cases. Hence, this gene should be promoted to green rating in the next GMS review.
Clefting v4.28 KAT6B Achchuthan Shanmugasundram Phenotypes for gene: KAT6B were changed from Genitopatellar syndrome, OMIM:606170; SBBYSS syndrome, OMIM:603736 to Genitopatellar syndrome, OMIM:606170; SBBYSS syndrome, OMIM:603736
Clefting v4.28 KAT6B Achchuthan Shanmugasundram Phenotypes for gene: KAT6B were changed from Genitopatellar syndrome, OMIM:606170; SBBYSS syndrome, OMIM:603736 to Genitopatellar syndrome, OMIM:606170; SBBYSS syndrome, OMIM:603736
Clefting v4.28 KAT6B Achchuthan Shanmugasundram Phenotypes for gene: KAT6B were changed from Genitopatellar syndrome, OMIM:606170; SBBYSS syndrome, OMIM:603736 to Genitopatellar syndrome, OMIM:606170; SBBYSS syndrome, OMIM:603736
Clefting v4.27 KAT6B Achchuthan Shanmugasundram Phenotypes for gene: KAT6B were changed from Genitopatellar syndrome, OMIM:606170; SBBYSS syndrome, OMIM:603736 to Genitopatellar syndrome, OMIM:606170; SBBYSS syndrome, OMIM:603736
Clefting v4.27 KAT6B Achchuthan Shanmugasundram Phenotypes for gene: KAT6B were changed from Genitopatellar syndrome, 606170; GTPTS to Genitopatellar syndrome, OMIM:606170; SBBYSS syndrome, OMIM:603736
Clefting v4.26 KAT6B Achchuthan Shanmugasundram Publications for gene: KAT6B were set to 20182757; 27031267; 32424177; 37010288
Clefting v4.26 KAT6B Achchuthan Shanmugasundram Publications for gene: KAT6B were set to 20182757; 27031267
Clefting v4.25 KAT6B Achchuthan Shanmugasundram reviewed gene: KAT6B: Rating: AMBER; Mode of pathogenicity: None; Publications: 32424177, 37010288; Phenotypes: Genitopatellar syndrome, OMIM:606170, SBBYSS syndrome, OMIM:603736; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Clefting v4.25 HNRNPK Achchuthan Shanmugasundram Classified gene: HNRNPK as Amber List (moderate evidence)
Clefting v4.25 HNRNPK Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available to promote this gene to green rating in the next GMS review.
Clefting v4.25 HNRNPK Achchuthan Shanmugasundram Gene: hnrnpk has been classified as Amber List (Moderate Evidence).
Clefting v4.24 HNRNPK Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: HNRNPK.
Clefting v4.24 HNRNPK Achchuthan Shanmugasundram Phenotypes for gene: HNRNPK were changed from Au-Kline syndrome, OMIM:616580 to Au-Kline syndrome, OMIM:616580
Clefting v4.24 HNRNPK Achchuthan Shanmugasundram Phenotypes for gene: HNRNPK were changed from to Au-Kline syndrome, OMIM:616580
Clefting v4.23 HNRNPK Achchuthan Shanmugasundram changed review comment from: PMID:29904177 reported six new cases and reviewed additional cases from literature with Au-Kline syndrome and monoallelic variants in HNRNPK gene. Of 12 patients reported and reviewed in this publication, five had cleft palate and two others had bifid uvula.

Three out of six patients reported with heterozygous sequence variants in HNRNPK gene had cleft palate as one of the phenotypes (PMID:37010288).

OMIM reported that patients with Au-Kline syndrome (MIM #616580) caused by autosomal dominant variants in HNRNPK gene has cleft palate/ bifid uvula as clinical manifestations.
Sources: Literature; to: PMID:29904177 reported six new cases and reviewed additional cases from literature with Au-Kline syndrome and monoallelic variants in HNRNPK gene. Of 12 patients reported and reviewed in this publication, five had cleft palate and two others had bifid uvula.

Three out of six patients reported with heterozygous sequence variants in HNRNPK gene in the DECIPHER database had cleft palate as one of the phenotypes (PMID:37010288).

OMIM reported that patients with Au-Kline syndrome (MIM #616580) caused by autosomal dominant variants in HNRNPK gene has cleft palate/ bifid uvula as clinical manifestations.
Sources: Literature
Clefting v4.23 HNRNPK Achchuthan Shanmugasundram edited their review of gene: HNRNPK: Changed phenotypes to: Au-Kline syndrome, OMIM:616580
Clefting v4.23 HNRNPK Achchuthan Shanmugasundram gene: HNRNPK was added
gene: HNRNPK was added to Clefting. Sources: Literature
Mode of inheritance for gene: HNRNPK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HNRNPK were set to 29904177; 37010288
Review for gene: HNRNPK was set to GREEN
Added comment: PMID:29904177 reported six new cases and reviewed additional cases from literature with Au-Kline syndrome and monoallelic variants in HNRNPK gene. Of 12 patients reported and reviewed in this publication, five had cleft palate and two others had bifid uvula.

Three out of six patients reported with heterozygous sequence variants in HNRNPK gene had cleft palate as one of the phenotypes (PMID:37010288).

OMIM reported that patients with Au-Kline syndrome (MIM #616580) caused by autosomal dominant variants in HNRNPK gene has cleft palate/ bifid uvula as clinical manifestations.
Sources: Literature
Autoinflammatory disorders v1.1 SEC23B Lauma Freimane gene: SEC23B was added
gene: SEC23B was added to Autoinflammatory disorders. Sources: Literature
Mode of inheritance for gene: SEC23B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SEC23B were set to 32098966
Phenotypes for gene: SEC23B were set to Dyserythropoietic anemia, congenital, type II
Review for gene: SEC23B was set to GREEN
Added comment: Sources: Literature
Autoinflammatory disorders v1.1 PRF1 Lauma Freimane gene: PRF1 was added
gene: PRF1 was added to Autoinflammatory disorders. Sources: Literature
Mode of inheritance for gene: PRF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRF1 were set to 32098966
Phenotypes for gene: PRF1 were set to Familial hemophagocytic lymphohistiocytosis-2 (FHL2) (OMIM: 603553)
Autoinflammatory disorders v1.1 GP6 Lauma Freimane gene: GP6 was added
gene: GP6 was added to Autoinflammatory disorders. Sources: Expert Review,Literature
Mode of inheritance for gene: GP6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GP6 were set to 32098966
Phenotypes for gene: GP6 were set to Platlet-type bleeding disorder-11
Review for gene: GP6 was set to GREEN
Added comment: Sources: Expert Review, Literature
Autoinflammatory disorders v1.1 IL17RA Lauma Freimane gene: IL17RA was added
gene: IL17RA was added to Autoinflammatory disorders. Sources: Literature
Mode of inheritance for gene: IL17RA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL17RA were set to 32098966
Phenotypes for gene: IL17RA were set to Immunodeficiency-51
Review for gene: IL17RA was set to GREEN
Added comment: Sources: Literature
Autoinflammatory disorders v1.1 ADA Lauma Freimane gene: ADA was added
gene: ADA was added to Autoinflammatory disorders. Sources: Literature
Mode of inheritance for gene: ADA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADA were set to 32098966
Phenotypes for gene: ADA were set to T(-), B(-), NK(-) severe combin immunodeficiency
Review for gene: ADA was set to GREEN
Added comment: Sources: Literature
Haematological malignancies cancer susceptibility v4.2 NAPRT Lauma Freimane gene: NAPRT was added
gene: NAPRT was added to Haematological malignancies cancer susceptibility. Sources: Literature
Mode of inheritance for gene: NAPRT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAPRT were set to 32098966
Phenotypes for gene: NAPRT were set to MDS/AML; inherited bone marrow failure series
Review for gene: NAPRT was set to GREEN
Added comment: Sources: Literature
Haematological malignancies cancer susceptibility v4.2 DNAH9 Lauma Freimane gene: DNAH9 was added
gene: DNAH9 was added to Haematological malignancies cancer susceptibility. Sources: Literature
Mode of inheritance for gene: DNAH9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAH9 were set to 32098966
Phenotypes for gene: DNAH9 were set to MDS/AML; inherited bone marrow failure (IBMF)
Review for gene: DNAH9 was set to GREEN
Added comment: Sources: Literature
Haematological malignancies cancer susceptibility v4.2 ADA Lauma Freimane gene: ADA was added
gene: ADA was added to Haematological malignancies cancer susceptibility. Sources: Literature
Mode of inheritance for gene: ADA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADA were set to 32098966
Phenotypes for gene: ADA were set to severe combined immunodeficiency
Added comment: A causative factor of T cell-negative, B cell-negative, natural killer cell-negative severe combined immunodeficiency.
Sources: Literature
Clefting v4.22 GLI2 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: GLI2.
Clefting v4.22 GLI2 Achchuthan Shanmugasundram Deleted their comment
Clefting v4.22 GLI2 Achchuthan Shanmugasundram Classified gene: GLI2 as Amber List (moderate evidence)
Clefting v4.22 GLI2 Achchuthan Shanmugasundram Added comment: Comment on list classification: Although cleating is a minor feature in patients reported with monoallelic GLI2 variants, it has been reported in more than 15 cases. Hence, this gene should be promoted to green rating in the next GMS review.
Clefting v4.22 GLI2 Achchuthan Shanmugasundram Gene: gli2 has been classified as Amber List (Moderate Evidence).
Clefting v4.21 GLI2 Achchuthan Shanmugasundram Classified gene: GLI2 as Amber List (moderate evidence)
Clefting v4.21 GLI2 Achchuthan Shanmugasundram Added comment: Comment on list classification: Although cleating is a minor feature in patients reported with monoallelic GLI2 variants, it has been reported in more than 15 cases. Hence, this gene should be promoted to green rating in the next GMS review.
Clefting v4.21 GLI2 Achchuthan Shanmugasundram Gene: gli2 has been classified as Amber List (Moderate Evidence).
Clefting v4.20 GLI2 Achchuthan Shanmugasundram gene: GLI2 was added
gene: GLI2 was added to Clefting. Sources: Literature
Mode of inheritance for gene: GLI2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GLI2 were set to 24744436; 37010288
Phenotypes for gene: GLI2 were set to Culler-Jones syndrome, OMIM:615849; Holoprosencephaly 9, OMIM:610829
Review for gene: GLI2 was set to GREEN
Added comment: In ~400 screened individuals with HPE spectrum disorders, 112 individuals were identified with variants in GLI2 gene, of which 16 cases had cleft lip/ palate (PMID:24744436).

Three out of 17 patients reported with heterozygous GLI2 sequence variants in the DECIPHER database presented with cleft lip/ palate as one of the phenotypes (PMID:37010288).

OMIM reported cleft lip/ palate as one of the clinical presentations in a subset of patients with Culler-Jones syndrome (MIM #615849) and holoprosencephaly 9 (MIM #610829). These are diseases associated with autosomal dominant variants in GLI2 gene.
Sources: Literature
Clefting v4.19 FGFR3 Achchuthan Shanmugasundram Deleted their comment
Clefting v4.19 FGFR3 Achchuthan Shanmugasundram Deleted their comment
Clefting v4.19 FGFR3 Achchuthan Shanmugasundram Classified gene: FGFR3 as Amber List (moderate evidence)
Clefting v4.19 FGFR3 Achchuthan Shanmugasundram Added comment: Comment on list classification: Although there are more than three unrelated cases reported with cleft lip and/or palate, this is not consistently found in patients with monoallelic variants in FGFR3 gene. Hence, this gene should be rated amber.
Clefting v4.19 FGFR3 Achchuthan Shanmugasundram Gene: fgfr3 has been classified as Amber List (Moderate Evidence).
Clefting v4.19 FGFR3 Achchuthan Shanmugasundram Deleted their comment
Clefting v4.19 FGFR3 Achchuthan Shanmugasundram Classified gene: FGFR3 as Amber List (moderate evidence)
Clefting v4.19 FGFR3 Achchuthan Shanmugasundram Added comment: Comment on list classification: Although there are more than three unrelated cases reported with cleft lip and/or palate, this is not consistently found in patients with monoallelic variants in FGFR3 gene. Hence, this gene should be rated amber.
Clefting v4.19 FGFR3 Achchuthan Shanmugasundram Gene: fgfr3 has been classified as Amber List (Moderate Evidence).
Clefting v4.18 FGFR3 Achchuthan Shanmugasundram Classified gene: FGFR3 as Amber List (moderate evidence)
Clefting v4.18 FGFR3 Achchuthan Shanmugasundram Added comment: Comment on list classification: Although there are more than three unrelated cases reported with cleft lip and/or palate, this is not consistently found in patients with monoallelic variants in FGFR3 gene. Hence, this gene should be rated amber.
Clefting v4.18 FGFR3 Achchuthan Shanmugasundram Gene: fgfr3 has been classified as Amber List (Moderate Evidence).
Clefting v4.18 FGFR3 Achchuthan Shanmugasundram Classified gene: FGFR3 as Amber List (moderate evidence)
Clefting v4.18 FGFR3 Achchuthan Shanmugasundram Added comment: Comment on list classification: Although there are more than three unrelated cases reported with cleft lip and/or palate, this is not consistently found in patients with monoallelic variants in FGFR3 gene. Hence, this gene should be rated amber.
Clefting v4.18 FGFR3 Achchuthan Shanmugasundram Gene: fgfr3 has been classified as Amber List (Moderate Evidence).
Congenital muscular dystrophy v4.9 COL4A1 Gavin Ryan reviewed gene: COL4A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18160688, 20818663; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Clefting v4.17 FGFR3 Achchuthan Shanmugasundram gene: FGFR3 was added
gene: FGFR3 was added to Clefting. Sources: Literature
Mode of inheritance for gene: FGFR3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FGFR3 were set to 22565872; 29150894; 37010288
Phenotypes for gene: FGFR3 were set to Muenke syndrome, OMIM:602849; Hypochondroplasia, OMIM:146000
Review for gene: FGFR3 was set to AMBER
Added comment: PMID:22565872 included 21 patients with variants in FGFR3 and presenting with Muenke syndrome in this study, of which 16 patients had structural anomaly of the palate. However, only one patient had cleft lip and palate.

PMID:29150894 reported a father and two children with FGFR3 variant and presenting with hypochondroplasia, of which only the daughter had cleft palate.

2 out of 15 patients reported in DECIPHER database with monoallelic sequence variants had cleft palate.
Sources: Literature
Clefting v4.16 CNTNAP1 Achchuthan Shanmugasundram changed review comment from: PMID:28374019 - Cleft palate was reported in two children from a large Israeli consanguineous family of Palestinian ancestry with a homozygous stop-gain variant in CNTNAP1(c.2015G>A/ p.Trp672Ter).

PMID:29511323/ 37010288 - There is one patient reported with compound heterozygous stop gain variants in CNTNAP1 (c.2687G​>A/ p.Trp896Ter & c.1861C​>T/ p.Arg621Ter) had cleft palate from DECIPHER database.

PMID:29882456 - An eight year old American male patient with a homozygous CNTNAP1 variant (c.1163G>C/ p.Arg388Pro) had cleft palate.
Sources: Literature; to: PMID:28374019 - Cleft palate was reported in two children from a large Israeli consanguineous family of Palestinian ancestry with a homozygous stop-gain variant in CNTNAP1(c.2015G>A/ p.Trp672Ter).

PMID:29511323/ 37010288 - There is one patient reported with compound heterozygous stop gain variants in CNTNAP1 (c.2687G​>A/ p.Trp896Ter & c.1861C​>T/ p.Arg621Ter) had cleft palate from DECIPHER database.

PMID:29882456 - An eight year old American male patient with a homozygous CNTNAP1 variant (c.1163G>C/ p.Arg388Pro) had cleft palate.
Sources: Literature
Clefting v4.16 CNTNAP1 Achchuthan Shanmugasundram changed review comment from: PMID:28374019 - Cleft palate was reported in two children from a large Israeli consanguineous family of Palestinian ancestry with a homozygous stop-gain variant in CNTNAP1(c.2015G>A/ p.Trp672Ter).

PMID:29511323/ 37010288 - A patient with compound heterozygous stop gain variants in CNTNAP1 gene (c.2687G​>A/ p.Trp896Ter & c.1861C​>T/ p.Arg621Ter) had cleft palate from DECIPHER database.

PMID:29882456 - An eight year old American male patient with a homozygous CNTNAP1 variant (c.1163G>C/ p.Arg388Pro) had cleft palate.
Sources: Literature; to: PMID:28374019 - Cleft palate was reported in two children from a large Israeli consanguineous family of Palestinian ancestry with a homozygous stop-gain variant in CNTNAP1(c.2015G>A/ p.Trp672Ter).

PMID:29511323/ 37010288 - There is one patient reported with compound heterozygous stop gain variants in CNTNAP1 (c.2687G​>A/ p.Trp896Ter & c.1861C​>T/ p.Arg621Ter) had cleft palate from DECIPHER database.

PMID:29882456 - An eight year old American male patient with a homozygous CNTNAP1 variant (c.1163G>C/ p.Arg388Pro) had cleft palate.
Sources: Literature
Clefting v4.16 CNTNAP1 Achchuthan Shanmugasundram changed review comment from: PMID:28374019 - Cleft palate was reported in two children from a large Israeli consanguineous family of Palestinian ancestry with a homozygous stop-gain variant in CNTNAP1(c.2015G>A/ p.Trp672Ter).

PMID:29511323/ 37010288 - Of seven patients reported with biallelic variants in CNTNAP1 gene, single patient with compound heterozygous stop gain variants (c.2687G​>A/ p.Trp896Ter & c.1861C​>T/ p.Arg621Ter) had cleft palate from DECIPHER database.

PMID:29882456 - An eight year old American male patient with a homozygous CNTNAP1 variant (c.1163G>C/ p.Arg388Pro) had cleft palate.
Sources: Literature; to: PMID:28374019 - Cleft palate was reported in two children from a large Israeli consanguineous family of Palestinian ancestry with a homozygous stop-gain variant in CNTNAP1(c.2015G>A/ p.Trp672Ter).

PMID:29511323/ 37010288 - A patient with compound heterozygous stop gain variants in CNTNAP1 gene (c.2687G​>A/ p.Trp896Ter & c.1861C​>T/ p.Arg621Ter) had cleft palate from DECIPHER database.

PMID:29882456 - An eight year old American male patient with a homozygous CNTNAP1 variant (c.1163G>C/ p.Arg388Pro) had cleft palate.
Sources: Literature
Clefting v4.16 CNTNAP1 Achchuthan Shanmugasundram edited their review of gene: CNTNAP1: Changed rating: GREEN
Clefting v4.16 CNTNAP1 Achchuthan Shanmugasundram changed review comment from: PMID:28374019 - Cleft palate was reported in two children from a large Israeli consanguineous family of Palestinian ancestry with a homozygous stop-gain variant in CNTNAP1(c.2015G>A/ p.Trp672Ter).

PMID:29511323/ 37010288 - There is one patient reported with compound heterozygous stop gain variants in CNTNAP1 (c.2687G​>A/ p.Trp896Ter & c.1861C​>T/ p.Arg621Ter) had cleft palate from DECIPHER database.

PMID:29882456 - An eight year old American male patient with a homozygous CNTNAP1 variant (c.1163G>C/ p.Arg388Pro) had cleft palate.
Sources: Literature; to: PMID:28374019 - Cleft palate was reported in two children from a large Israeli consanguineous family of Palestinian ancestry with a homozygous stop-gain variant in CNTNAP1(c.2015G>A/ p.Trp672Ter).

PMID:29511323/ 37010288 - Of seven patients reported with biallelic variants in CNTNAP1 gene, single patient with compound heterozygous stop gain variants (c.2687G​>A/ p.Trp896Ter & c.1861C​>T/ p.Arg621Ter) had cleft palate from DECIPHER database.

PMID:29882456 - An eight year old American male patient with a homozygous CNTNAP1 variant (c.1163G>C/ p.Arg388Pro) had cleft palate.
Sources: Literature
Clefting v4.16 CNTNAP1 Achchuthan Shanmugasundram edited their review of gene: CNTNAP1: Changed rating: AMBER
Clefting v4.16 ARID1B Achchuthan Shanmugasundram changed review comment from: Comment on list classification: Although there are three unrelated cases reported, clefting is not consistently present in patients with monoallelic variants in this gene. Hence, this gene should be rated amber.; to: Comment on list classification: Although there are more than three unrelated cases reported, clefting is not consistently present in patients with monoallelic variants in this gene. Hence, this gene should be rated amber.
Clefting v4.16 ARID1B Achchuthan Shanmugasundram changed review comment from: PMID:30349098 - On this web-based survey based on previously reported features of patients with variants in ARID1B gene (143 patients in total), which also included submissions to DECIPHER database, two patients were identified with cleft palate, one with cleft uvula, two with bifid uvula and three with sub mucous cleft. Although variants identified in these patients are reported in this publication, there is no association of individual patients to phenotypes available.

One patient with ARID1B variant (c.3183_3184​insT/ p.Tyr1062LeufsTer10) was reported with submucous cleft soft palate and two patients with ARID1B variants (c.4155_4156​insA/ p.Asn1386LysfsTer18 & c.2620+5G​>A) were reported with bifid uvula in DECIPHER database.
Sources: Literature; to: PMID:30349098 - On this web-based survey based on previously reported features of patients with variants in ARID1B gene (143 patients in total), which also included submissions to DECIPHER database, two patients were identified with cleft palate, one with cleft uvula, two with bifid uvula and three with sub mucous cleft. Although variants identified in these patients are reported in this publication, there is no association of individual patients to phenotypes available.

Of >100 patients with ARID1B variants in the DECIPHER database, only one patient (c.3183_3184​insT/ p.Tyr1062LeufsTer10) was reported with submucous cleft soft palate and two patients (c.4155_4156​insA/ p.Asn1386LysfsTer18 & c.2620+5G​>A) were reported with bifid uvula.
Sources: Literature
Clefting v4.16 ARID1B Achchuthan Shanmugasundram Classified gene: ARID1B as Amber List (moderate evidence)
Clefting v4.16 ARID1B Achchuthan Shanmugasundram Added comment: Comment on list classification: Although there are three unrelated cases reported, clefting is not consistently present in patients with monoallelic variants in this gene. Hence, this gene should be rated amber.
Clefting v4.16 ARID1B Achchuthan Shanmugasundram Gene: arid1b has been classified as Amber List (Moderate Evidence).
Clefting v4.15 ARID1B Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: ARID1B.
Clefting v4.15 ARID1B Achchuthan Shanmugasundram Deleted their comment
Clefting v4.15 ARID1B Achchuthan Shanmugasundram edited their review of gene: ARID1B: Changed rating: AMBER
Clefting v4.15 CHD4 Achchuthan Shanmugasundram Deleted their comment
Clefting v4.15 CHD4 Achchuthan Shanmugasundram Classified gene: CHD4 as Amber List (moderate evidence)
Clefting v4.15 CHD4 Achchuthan Shanmugasundram Added comment: Comment on list classification: Although there are four unrelated cases presenting with either cleft palate and/or bifid uvula, this phenotype is not consistently found in patients with monoallelic CHD4 variants. Hence, this gene should be rated amber.
Clefting v4.15 CHD4 Achchuthan Shanmugasundram Gene: chd4 has been classified as Amber List (Moderate Evidence).
Clefting v4.14 CHD4 Achchuthan Shanmugasundram Classified gene: CHD4 as Amber List (moderate evidence)
Clefting v4.14 CHD4 Achchuthan Shanmugasundram Added comment: Comment on list classification: Although there are four unrelated cases presenting with either cleft palate and/or bifid uvula, this phenotype is not consistently found in patients with monoallelic CHD4 variants. Hence, this gene should be rated amber.
Clefting v4.14 CHD4 Achchuthan Shanmugasundram Gene: chd4 has been classified as Amber List (Moderate Evidence).
Clefting v4.13 CHD4 Achchuthan Shanmugasundram Deleted their comment
Clefting v4.13 CHD4 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: CHD4.
Clefting v4.13 CHD4 Achchuthan Shanmugasundram edited their review of gene: CHD4: Changed rating: AMBER
Clefting v4.13 CHD4 Achchuthan Shanmugasundram changed review comment from: PMID:31388190 reported a patient with heterozygous variant (p.Gln715Ter) in CHD4 that had cleft palate and pierre robin. In addition, another patient identified with heterozygous variant p.Arg1127Gln was reported with bifid uvula.

In addition, DDD study reported two patients with likely pathogenic heterozygous variants who had cleft palate in addition to several other clinical presentations including global developmental delay (PMID:37010288).
Sources: Literature; to: PMID:31388190 reported 32 patients with heterozygous variants in CHD4 gene, of which one patient (p.Gln715Ter) had cleft palate and pierre robin. In addition, another patient identified with heterozygous variant p.Arg1127Gln was reported with bifid uvula.

In addition, 2 out of 10 patients with pathogenic/ likely pathogenic heterozygous variants from the DDD study were reported with cleft palate in addition to several other clinical presentations including global developmental delay (PMID:37010288).
Sources: Literature
Clefting v4.13 CHD4 Achchuthan Shanmugasundram changed review comment from: PMID:3138819 reported a patient with heterozygous variant (p.Gln715Ter) in CHD4 that had cleft palate and pierre robin. In addition, another patient identified with heterozygous variant p.Arg1127Gln was reported with bifid uvula.

In addition, DDD study reported two patients with likely pathogenic heterozygous variants who had cleft palate in addition to several other clinical presentations including global developmental delay (PMID:37010288).
Sources: Literature; to: PMID:31388190 reported a patient with heterozygous variant (p.Gln715Ter) in CHD4 that had cleft palate and pierre robin. In addition, another patient identified with heterozygous variant p.Arg1127Gln was reported with bifid uvula.

In addition, DDD study reported two patients with likely pathogenic heterozygous variants who had cleft palate in addition to several other clinical presentations including global developmental delay (PMID:37010288).
Sources: Literature
Clefting v4.13 B4GALT7 Achchuthan Shanmugasundram Publications for gene: B4GALT7 were set to 24755949
Clefting v4.12 B4GALT7 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: B4GALT7.
Clefting v4.12 B4GALT7 Achchuthan Shanmugasundram changed review comment from: PMID:24755949 - One of 22 patients identified with homozygous p.Arg270Cys variant in B4GALT7 gene had a cleft palate.
PMID:26940150 - One of two patients reported in this publication from DDD study with compound heterozygous variants (p.His93Profds*73 & p.Cys2145Tyr) had cleft palate.
PMID:31278392 - One patient and affected third pregnancy with compound heterozygous variants (p.Gln133Arg & p.Arg270Cys) and cleft palate was reported in this family.; to: Cleft palate is not a consistent feature that is reported in patients with biallelic variants in B4GALT7 gene. However, there are three unrelated cases reported with cleft palate.

PMID:24755949 - One of 22 patients identified with homozygous p.Arg270Cys variant in B4GALT7 gene had a cleft palate.
PMID:26940150 - One of two patients reported in this publication from DDD study with compound heterozygous variants (p.His93Profds*73 & p.Cys2145Tyr) had cleft palate.
PMID:31278392 - One patient and affected third pregnancy with compound heterozygous variants (p.Gln133Arg & p.Arg270Cys) and cleft palate was reported in this family.
Clefting v4.12 B4GALT7 Achchuthan Shanmugasundram edited their review of gene: B4GALT7: Changed rating: AMBER
Clefting v4.12 B4GALT7 Achchuthan Shanmugasundram Deleted their comment
Clefting v4.12 B4GALT7 Achchuthan Shanmugasundram changed review comment from: PMID:24755949 - One of 22 patients identified with with homozygous p.Arg270Cys variant in B4GALT7 gene had a cleft palate.
PMID:26940150 - One of two patients reported in this publication from DDD study with compound heterozygous variants (p.His93Profds*73 & p.Cys2145Tyr) had cleft palate.
PMID:31278392 - One patient and affected third pregnancy with compound heterozygous variants (p.Gln133Arg & p.Arg270Cys) and cleft palate was reported in this family.; to: PMID:24755949 - One of 22 patients identified with homozygous p.Arg270Cys variant in B4GALT7 gene had a cleft palate.
PMID:26940150 - One of two patients reported in this publication from DDD study with compound heterozygous variants (p.His93Profds*73 & p.Cys2145Tyr) had cleft palate.
PMID:31278392 - One patient and affected third pregnancy with compound heterozygous variants (p.Gln133Arg & p.Arg270Cys) and cleft palate was reported in this family.
Clefting v4.12 DDX3X Achchuthan Shanmugasundram changed review comment from: PMID:26235985 - Patients with DDX3X variants reported from multiple studies including the Deciphering Developmental Disorders (DDD) study, of which three females had cleft lip and/ or palate (one from the DDD study) and one male had bifid uvula.

PMID:27159028 - A female patient with DDX3X variant (c.856G>A/ p.Gly286Ser) and reported with severe ID and ataxic gait also had cleft uvula.; to: PMID:26235985 - 38 female and three male patients with DDX3X variants were reported from multiple studies including the Deciphering Developmental Disorders (DDD) study, of which three females had cleft lip and/ or palate (one from the DDD study) and one male had bifid uvula.

PMID:27159028 - Two female patients were reported with DDX3X variants, of which one of them reported with severe ID and ataxic gait (c.856G>A/ p.Gly286Ser) also had cleft uvula.
Clefting v4.12 DDX3X Achchuthan Shanmugasundram edited their review of gene: DDX3X: Changed rating: AMBER
Clefting v4.12 DDX3X Achchuthan Shanmugasundram Deleted their comment
Clefting v4.12 DDX3X Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: DDX3X.
Ehlers Danlos syndrome with a likely monogenic cause v3.3 COL12A1 Sarah Leigh Publications for gene: COL12A1 were set to 28306229; 28306225; 24334769; 24334604; 27348394
Ehlers Danlos syndrome with a likely monogenic cause v3.2 COL12A1 Sarah Leigh reviewed gene: COL12A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35019233; Phenotypes: ; Mode of inheritance: None
Ehlers Danlos syndrome with a likely monogenic cause v3.2 COL12A1 Sarah Leigh Phenotypes for gene: COL12A1 were changed from Bethlem myopathy 2, OMIM:616471 to Bethlem myopathy 2, OMIM:616471; Bethlem myopathy 2, MONDO:0034022
Haematological malignancies cancer susceptibility v4.2 DHX34 Lauma Freimane gene: DHX34 was added
gene: DHX34 was added to Haematological malignancies cancer susceptibility. Sources: Literature
Mode of inheritance for gene: DHX34 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DHX34 were set to 32098966
Phenotypes for gene: DHX34 were set to Thrombocytopenia; Neutropenia; Pancytopenia; AML
Penetrance for gene: DHX34 were set to Complete
Review for gene: DHX34 was set to GREEN
Added comment: PMID: 32098966 - "[..] functionally validated heterozygous variants in the RNA helicase DHX34, detected in four families, all of which impacted activity of the NMD (nonsense-mediated mRNA decay) pathway. [..]"
Sources: Literature
Haematological malignancies cancer susceptibility v4.2 SH2B3 Lauma Freimane reviewed gene: SH2B3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Clefting v4.12 DDX3X Achchuthan Shanmugasundram Deleted their comment
Clefting v4.12 DDX3X Achchuthan Shanmugasundram Classified gene: DDX3X as Amber List (moderate evidence)
Clefting v4.12 DDX3X Achchuthan Shanmugasundram Added comment: Comment on list classification: There are five unrelated cases associating this gene with cleft lip and/ or palate. Hence, this gene can be promoted to green rating at the next major update.
Clefting v4.12 DDX3X Achchuthan Shanmugasundram Gene: ddx3x has been classified as Amber List (Moderate Evidence).
Clefting v4.12 DDX3X Achchuthan Shanmugasundram Classified gene: DDX3X as Amber List (moderate evidence)
Clefting v4.12 DDX3X Achchuthan Shanmugasundram Added comment: Comment on list classification: There are five unrelated cases associating this gene with cleft lip and/ or palate. Hence, this gene can be promoted to green rating at the next major update.
Clefting v4.12 DDX3X Achchuthan Shanmugasundram Gene: ddx3x has been classified as Amber List (Moderate Evidence).
Clefting v4.11 DDX3X Achchuthan Shanmugasundram Publications for gene: DDX3X were set to 26235985; 27159028; 37010288
Clefting v4.11 DDX3X Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: DDX3X.
Clefting v4.11 DDX3X Achchuthan Shanmugasundram Publications for gene: DDX3X were set to 26235985; 27159028; 37010288
Clefting v4.11 DDX3X Achchuthan Shanmugasundram Publications for gene: DDX3X were set to 26235985; 27159028; 37010288
Clefting v4.11 DDX3X Achchuthan Shanmugasundram Publications for gene: DDX3X were set to
Clefting v4.10 DDX3X Achchuthan Shanmugasundram reviewed gene: DDX3X: Rating: GREEN; Mode of pathogenicity: None; Publications: 26235985, 27159028, 37010288; Phenotypes: Intellectual developmental disorder, X-linked syndromic, Snijders Blok type, OMIM:300958; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Clefting v4.10 CNTNAP1 Achchuthan Shanmugasundram Classified gene: CNTNAP1 as Amber List (moderate evidence)
Clefting v4.10 CNTNAP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (3 unrelated cases) for the association of biallelic variants from this gene with cleft palate. Hence, it can be promoted to green rating at the next major update.
Clefting v4.10 CNTNAP1 Achchuthan Shanmugasundram Gene: cntnap1 has been classified as Amber List (Moderate Evidence).
Clefting v4.9 CNTNAP1 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: CNTNAP1.
Clefting v4.9 CNTNAP1 Achchuthan Shanmugasundram gene: CNTNAP1 was added
gene: CNTNAP1 was added to Clefting. Sources: Literature
Mode of inheritance for gene: CNTNAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CNTNAP1 were set to 28374019; 29511323; 29882456; 37010288
Phenotypes for gene: CNTNAP1 were set to Hypomyelinating neuropathy, congenital, 3, OMIM:618186
Review for gene: CNTNAP1 was set to GREEN
Added comment: PMID:28374019 - Cleft palate was reported in two children from a large Israeli consanguineous family of Palestinian ancestry with a homozygous stop-gain variant in CNTNAP1(c.2015G>A/ p.Trp672Ter).

PMID:29511323/ 37010288 - There is one patient reported with compound heterozygous stop gain variants in CNTNAP1 (c.2687G​>A/ p.Trp896Ter & c.1861C​>T/ p.Arg621Ter) had cleft palate from DECIPHER database.

PMID:29882456 - An eight year old American male patient with a homozygous CNTNAP1 variant (c.1163G>C/ p.Arg388Pro) had cleft palate.
Sources: Literature
Clefting v4.8 ARID1B Achchuthan Shanmugasundram Classified gene: ARID1B as Amber List (moderate evidence)
Clefting v4.8 ARID1B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (at least three unrelated cases) for this gene to be promoted to green rating at the next major review.
Clefting v4.8 ARID1B Achchuthan Shanmugasundram Gene: arid1b has been classified as Amber List (Moderate Evidence).
Clefting v4.7 ARID1B Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: ARID1B.
Clefting v4.7 ARID1B Achchuthan Shanmugasundram edited their review of gene: ARID1B: Changed rating: GREEN
Clefting v4.7 ARID1B Achchuthan Shanmugasundram changed review comment from: PMID:30349098 - On this web-based survey based on previously reported features of patients with variants in ARID1B gene (143 patients in total), which also included submissions to DECIPHER database, two patients were identified with cleft palate, one with cleft uvula, two with bifid uvula and three with sub mucous cleft. Although variants identified in these patients are reported in this publication, there is no association of individual patients to phenotypes available.

One patient was reported with submucous cleft soft palate and two patients were reported with bifid uvula in DECIPHER database.
Sources: Literature; to: PMID:30349098 - On this web-based survey based on previously reported features of patients with variants in ARID1B gene (143 patients in total), which also included submissions to DECIPHER database, two patients were identified with cleft palate, one with cleft uvula, two with bifid uvula and three with sub mucous cleft. Although variants identified in these patients are reported in this publication, there is no association of individual patients to phenotypes available.

One patient with ARID1B variant (c.3183_3184​insT/ p.Tyr1062LeufsTer10) was reported with submucous cleft soft palate and two patients with ARID1B variants (c.4155_4156​insA/ p.Asn1386LysfsTer18 & c.2620+5G​>A) were reported with bifid uvula in DECIPHER database.
Sources: Literature
Clefting v4.7 ARID1B Achchuthan Shanmugasundram changed review comment from: PMID:30349098 - On this web-based survey based on previously reported features of patients with variants in ARID1B gene (143 patients in total), which also included submissions to DECIPHER database, two patients were identified with cleft palate, one with cleft uvula, two with bifid uvula and three with sub mucous cleft. Although variants identified in these patients are reported in this publication, there is no association of individual patients to phenotypes available.

There is only one patient reported with pathogenic variant in ARID1B gene and submucous cleft soft palate in DECIPHER database.
Sources: Literature; to: PMID:30349098 - On this web-based survey based on previously reported features of patients with variants in ARID1B gene (143 patients in total), which also included submissions to DECIPHER database, two patients were identified with cleft palate, one with cleft uvula, two with bifid uvula and three with sub mucous cleft. Although variants identified in these patients are reported in this publication, there is no association of individual patients to phenotypes available.

One patient was reported with submucous cleft soft palate and two patients were reported with bifid uvula in DECIPHER database.
Sources: Literature
Clefting v4.7 ARID1B Achchuthan Shanmugasundram gene: ARID1B was added
gene: ARID1B was added to Clefting. Sources: Literature
Mode of inheritance for gene: ARID1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARID1B were set to 30349098; 37010288
Phenotypes for gene: ARID1B were set to Coffin-Siris syndrome 1, OMIM:135900
Review for gene: ARID1B was set to AMBER
Added comment: PMID:30349098 - On this web-based survey based on previously reported features of patients with variants in ARID1B gene (143 patients in total), which also included submissions to DECIPHER database, two patients were identified with cleft palate, one with cleft uvula, two with bifid uvula and three with sub mucous cleft. Although variants identified in these patients are reported in this publication, there is no association of individual patients to phenotypes available.

There is only one patient reported with pathogenic variant in ARID1B gene and submucous cleft soft palate in DECIPHER database.
Sources: Literature
Clefting v4.6 CHD4 Achchuthan Shanmugasundram changed review comment from: PMID:3138819 reported a patient with heterozygous variant (p.Gln715Ter) in CHD4 that had cleft palate and pierre robin. In addition, another patient identified with heterozygous variant p.Arg1127Gln was reported with bifid uvula.

In addition, DDD study reported two patients with likely pathogenic heterozygous variants who had cleft palate in addition to several other clinical presentations including global developmental delay (PMID:37010288)
Sources: Literature; to: PMID:3138819 reported a patient with heterozygous variant (p.Gln715Ter) in CHD4 that had cleft palate and pierre robin. In addition, another patient identified with heterozygous variant p.Arg1127Gln was reported with bifid uvula.

In addition, DDD study reported two patients with likely pathogenic heterozygous variants who had cleft palate in addition to several other clinical presentations including global developmental delay (PMID:37010288).
Sources: Literature
Clefting v4.6 CHD4 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: CHD4.
Clefting v4.6 CHD4 Achchuthan Shanmugasundram Classified gene: CHD4 as Amber List (moderate evidence)
Clefting v4.6 CHD4 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are four unrelated cases presenting with either cleft palate and/or bifid uvula. Hence, this gene can be promoted to green at the next major review.
Clefting v4.6 CHD4 Achchuthan Shanmugasundram Gene: chd4 has been classified as Amber List (Moderate Evidence).
Clefting v4.5 CHD4 Achchuthan Shanmugasundram gene: CHD4 was added
gene: CHD4 was added to Clefting. Sources: Literature
Mode of inheritance for gene: CHD4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHD4 were set to 31388190; 37010288
Phenotypes for gene: CHD4 were set to Sifrim-Hitz-Weiss syndrome, OMIM:617159
Review for gene: CHD4 was set to GREEN
Added comment: PMID:3138819 reported a patient with heterozygous variant (p.Gln715Ter) in CHD4 that had cleft palate and pierre robin. In addition, another patient identified with heterozygous variant p.Arg1127Gln was reported with bifid uvula.

In addition, DDD study reported two patients with likely pathogenic heterozygous variants who had cleft palate in addition to several other clinical presentations including global developmental delay (PMID:37010288)
Sources: Literature
Clefting v4.4 B4GALT7 Achchuthan Shanmugasundram Deleted their comment
Clefting v4.4 B4GALT7 Achchuthan Shanmugasundram Classified gene: B4GALT7 as Amber List (moderate evidence)
Clefting v4.4 B4GALT7 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (3 unrelated cases) for this gene to be promoted to Green rating at the next major review.
Clefting v4.4 B4GALT7 Achchuthan Shanmugasundram Gene: b4galt7 has been classified as Amber List (Moderate Evidence).
Clefting v4.3 B4GALT7 Achchuthan Shanmugasundram Classified gene: B4GALT7 as Amber List (moderate evidence)
Clefting v4.3 B4GALT7 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (3 unrelated cases) for this gene to be promoted to Green rating at the next major review.
Clefting v4.3 B4GALT7 Achchuthan Shanmugasundram Gene: b4galt7 has been classified as Amber List (Moderate Evidence).
Clefting v4.2 B4GALT7 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: B4GALT7.
Clefting v4.2 B4GALT7 Achchuthan Shanmugasundram reviewed gene: B4GALT7: Rating: GREEN; Mode of pathogenicity: None; Publications: 24755949, 26940150, 31278392; Phenotypes: Ehlers-Danlos syndrome, spondylodysplastic type, 1, OMIM:130070; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.189 TTI1 Sarah Leigh Classified gene: TTI1 as Amber List (moderate evidence)
Intellectual disability v5.189 TTI1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Intellectual disability v5.189 TTI1 Sarah Leigh Gene: tti1 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v4.27 TTI1 Sarah Leigh Classified gene: TTI1 as Amber List (moderate evidence)
Severe microcephaly v4.27 TTI1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Severe microcephaly v4.27 TTI1 Sarah Leigh Gene: tti1 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v4.26 TTI1 Sarah Leigh Tag Q3_23_promote_green tag was added to gene: TTI1.
Intellectual disability v5.188 TTI1 Sarah Leigh Tag Q3_23_promote_green tag was added to gene: TTI1.
Severe microcephaly v4.26 TTI1 Sarah Leigh gene: TTI1 was added
gene: TTI1 was added to Severe microcephaly. Sources: Literature
Mode of inheritance for gene: TTI1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTI1 were set to 36724785
Phenotypes for gene: TTI1 were set to neurodevelopmental disorder with microcephaly
Review for gene: TTI1 was set to GREEN
Added comment: TTI1 has not previously been associated with a phenotype in OMIM, Gen2Phen or MONDO. At least 2 variants have been reported. PMID: 36724785 reported 15 TTI1 variants as either homozygotes (2 families) or compound heterozygotes (7 families) in cases with a neurodevelopmental disorder with microcephaly. In all cases the parents were heterozygous carriers of the TTI1 variant identified in the affected child. Development delay was observed in all of the families (9/9), moderate to severe intellectual disability was evident in all families where it could be assessed (8/8) and severe microcephaly was present in members of 5/9 families. Supportive functional results were also presented.
Sources: Literature
Intellectual disability v5.188 TTI1 Sarah Leigh gene: TTI1 was added
gene: TTI1 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: TTI1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTI1 were set to 36724785
Phenotypes for gene: TTI1 were set to neurodevelopmental disorder with microcephaly
Review for gene: TTI1 was set to GREEN
Added comment: TTI1 has not previously been associated with a phenotype in OMIM, Gen2Phen or MONDO. At least 2 variants have been reported. PMID: 36724785 reported 15 TTI1 variants as either homozygotes (2 families) or compound heterozygotes (7 families) in cases with a neurodevelopmental disorder with microcephaly. In all cases the parents were heterozygous carriers of the TTI1 variant identified in the affected child. Development delay was observed in all of the families (9/9), moderate to severe intellectual disability was evident in all families where it could be assessed (8/8) and severe microcephaly was present in members of 5/9 families. Supportive functional results were also presented.
Sources: Literature
Intellectual disability v5.187 TSPOAP1 Sarah Leigh Tag Q3_23_promote_green tag was added to gene: TSPOAP1.
Dystonia, chorea or related movement disorder, childhood onset v3.13 TSPOAP1 Sarah Leigh Tag Q3_23_promote_green tag was added to gene: TSPOAP1.
Intellectual disability v5.187 TSPOAP1 Sarah Leigh Entity copied from Childhood onset dystonia, chorea or related movement disorder v3.13
Intellectual disability v5.187 TSPOAP1 Sarah Leigh gene: TSPOAP1 was added
gene: TSPOAP1 was added to Intellectual disability - microarray and sequencing. Sources: Literature,Expert Review Amber
Mode of inheritance for gene: TSPOAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TSPOAP1 were set to 33539324
Phenotypes for gene: TSPOAP1 were set to Dystonia, intellectual disability and cerebellar atrophy
Dystonia, chorea or related movement disorder, childhood onset v3.13 TSPOAP1 Sarah Leigh Tag Q3_23_promote_green was removed from TSPOAP1.
Dystonia, chorea or related movement disorder, childhood onset v3.12 TSPOAP1 Sarah Leigh changed review comment from: Not associated with a phenotype in OMIM, Gen2Phen or MONDO. At least TSPOAP1 three variants have been reported in three unrelated families. Family members carrying homozygous TSPOAP1 variants have dystonia, intellectual disability and cerebellar atrophy to varying degrees. Motor symptoms were apparent between 11 and 13 years of age for NM_004758: c.2449_2450delinsTG, p.Gln817* and c.538delG, p.Ala180Profs*8, while NM_004758: c.5422G>A, p.Gly1808Ser was from 58 years through to the 60s. Similarly, cognitive impairment was apparent from school age and progressed to moderate to extensive, in the carries of the two terminating TSPOAP1 variants, while those with the missense variant were diagnosed with mild cognitive impairment (PMID: 33539324). In vitro functional studies and mouse models support the association of the TSPOAP1 variants and phenotypes seen in the cases (PMID: 33539324).; to: Not associated with a phenotype in OMIM, Gen2Phen or MONDO. At least three TSPOAP1variants have been reported in three unrelated families. Family members carrying homozygous TSPOAP1 variants have dystonia, intellectual disability and cerebellar atrophy to varying degrees. Motor symptoms were apparent between 11 and 13 years of age for NM_004758: c.2449_2450delinsTG, p.Gln817* and c.538delG, p.Ala180Profs*8, while NM_004758: c.5422G>A, p.Gly1808Ser was from 58 years through to the 60s. Similarly, cognitive impairment was apparent from school age and progressed to moderate to extensive, in the carries of the two terminating TSPOAP1 variants, while those with the missense variant were diagnosed with mild cognitive impairment (PMID: 33539324). In vitro functional studies and mouse models support the association of the TSPOAP1 variants and phenotypes seen in the cases (PMID: 33539324).
Dystonia, chorea or related movement disorder, childhood onset v3.12 TSPOAP1 Sarah Leigh changed review comment from: Not associated with a phenotype in OMIM, Gen2Phen or MONDO. At least TSPOAP1 three variants have been reported in three unrelated families. Family members carrying homozygous TSPOAP1 variants have dystonia, intellectual disability and cerebellar atrophy to varying degrees (PMID: 33539324). In vitro functional studies and mouse models support the association of the TSPOAP1 variants and phenotypes seen in the cases (PMID: 33539324).; to: Not associated with a phenotype in OMIM, Gen2Phen or MONDO. At least TSPOAP1 three variants have been reported in three unrelated families. Family members carrying homozygous TSPOAP1 variants have dystonia, intellectual disability and cerebellar atrophy to varying degrees. Motor symptoms were apparent between 11 and 13 years of age for NM_004758: c.2449_2450delinsTG, p.Gln817* and c.538delG, p.Ala180Profs*8, while NM_004758: c.5422G>A, p.Gly1808Ser was from 58 years through to the 60s. Similarly, cognitive impairment was apparent from school age and progressed to moderate to extensive, in the carries of the two terminating TSPOAP1 variants, while those with the missense variant were diagnosed with mild cognitive impairment (PMID: 33539324). In vitro functional studies and mouse models support the association of the TSPOAP1 variants and phenotypes seen in the cases (PMID: 33539324).
Dystonia, chorea or related movement disorder, childhood onset v3.12 TSPOAP1 Sarah Leigh Tag Q3_23_promote_green tag was added to gene: TSPOAP1.
Dystonia, chorea or related movement disorder, childhood onset v3.12 TSPOAP1 Sarah Leigh edited their review of gene: TSPOAP1: Added comment: Not associated with a phenotype in OMIM, Gen2Phen or MONDO. At least TSPOAP1 three variants have been reported in three unrelated families. Family members carrying homozygous TSPOAP1 variants have dystonia, intellectual disability and cerebellar atrophy to varying degrees (PMID: 33539324). In vitro functional studies and mouse models support the association of the TSPOAP1 variants and phenotypes seen in the cases (PMID: 33539324).; Changed rating: GREEN
Dystonia, chorea or related movement disorder, childhood onset v3.12 TSPOAP1 Sarah Leigh Classified gene: TSPOAP1 as Amber List (moderate evidence)
Dystonia, chorea or related movement disorder, childhood onset v3.12 TSPOAP1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Dystonia, chorea or related movement disorder, childhood onset v3.12 TSPOAP1 Sarah Leigh Gene: tspoap1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.186 SRRM2 Sarah Leigh Added comment: Comment on publications: www.hindawi.com/journals/humu/2023/6633248
Intellectual disability v5.186 SRRM2 Sarah Leigh Publications for gene: SRRM2 were set to 35567594; 33057194
Hereditary ataxia, adult onset v4.12 FGF14_GAA Eleanor Williams changed review comment from: Comment on list classification: Promoting to amber but there is sufficient evidence to promote to green following GMS review, and configuration in the Rare Disease analysis pipeline.; to: Comment on list classification: Promoting to amber but there is sufficient evidence to promote to green following GMS review, and configuration in the Rare Disease analysis pipeline. GMS expert review is required to confirm that the normal and pathogenic thresholds set are appropriate.
Haematological malignancies cancer susceptibility v4.2 TCF3 Lauma Freimane gene: TCF3 was added
gene: TCF3 was added to Haematological malignancies cancer susceptibility. Sources: Literature
Mode of inheritance for gene: TCF3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TCF3 were set to 36576946
Phenotypes for gene: TCF3 were set to B-cell acute lymphoblastic leukemia
Penetrance for gene: TCF3 were set to unknown
Review for gene: TCF3 was set to GREEN
gene: TCF3 was marked as current diagnostic
Added comment: Autors hypothesize that variants in TCF3 gene alter B-cell maturation which may increase the risk for preleukemic clone emergence (PMID: 36576946).
Sources: Literature
Early onset or syndromic epilepsy v4.50 PNPO Achchuthan Shanmugasundram Publications for gene: PNPO were set to 24658933; 28818555; 22196487; 21704546; 25296925; 26535729; 15772097; 24266778; 36106796
Early onset or syndromic epilepsy v4.49 PNPO Achchuthan Shanmugasundram Publications for gene: PNPO were set to 24658933; 28818555; 22196487; 21704546; 25296925; 26535729; 15772097; 24266778; 36106796
Early onset or syndromic epilepsy v4.49 PNPO Achchuthan Shanmugasundram Publications for gene: PNPO were set to 24658933; 28818555; 22196487; 21704546; 25296925; 26535729; 15772097; 24266778
Dilated and arrhythmogenic cardiomyopathy v2.10 PPA2 Matthew Edwards gene: PPA2 was added
gene: PPA2 was added to Dilated and arrhythmogenic cardiomyopathy. Sources: Expert Review
Mode of inheritance for gene: PPA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPA2 were set to PMID: 34400813
Phenotypes for gene: PPA2 were set to Sudden cardiac failure, infantile; Sudden cardiac failure, alcohol-induced
Penetrance for gene: PPA2 were set to unknown
Review for gene: PPA2 was set to GREEN
gene: PPA2 was marked as current diagnostic
Added comment: Now a well established gene causing infantile sudden death, but can also manifest at a later age as alcohol-induced sudden death. Our lab and others have found several bi-allelic pathogenic variants in such SCD cases (see above ref). Is currently on syndromic/paediatric cardiomyopathy panel (R135) and mitochindrial panels, but wholly appropriate for this panel as well
Sources: Expert Review
Hereditary spastic paraplegia, adult onset v3.10 PRNP Sarah Leigh edited their review of gene: PRNP: Added comment: Amongst the variable phenotypes seen in carriers of PRNP variants, features of Gerstmann-Straussler disease (OMIM: 137440) have been associated with eight PRNP variants in unrelated cases (p.P105L, p.D178N, p.P102L, p.A117V, p.F198S, p.Q217R, p.G131V, p.H187R (PMIDs: 7902971, 1699173, 1363810, 11709001, 7902972, 19228673).; Changed rating: GREEN; Changed phenotypes to: Gerstmann-Straussler disease, OMIM: 137440
Hereditary spastic paraplegia, adult onset v3.10 PRNP Sarah Leigh Publications for gene: PRNP were set to 30240140; 8250529; 34746379; 28195350; 16227536; 19228673; 1699173; 7902971; 11709001; 10581485; 10953183; 1363810
Hereditary spastic paraplegia, adult onset v3.9 PRNP Sarah Leigh Publications for gene: PRNP were set to 30240140; 8250529; 34746379; 28195350; 16227536; 19228673; 1699173; 7902971; 11709001; 10581485; 10953183
Hereditary spastic paraplegia, adult onset v3.8 PRNP Sarah Leigh Phenotypes for gene: PRNP were changed from Gerstmann-Straussler disease, OMIM: 137440 to Gerstmann-Straussler disease, OMIM: 137440; Gerstmann-Straussler-Scheinker syndrome, MONDO:0007656
Hereditary spastic paraplegia, adult onset v3.7 PRNP Sarah Leigh Classified gene: PRNP as Amber List (moderate evidence)
Hereditary spastic paraplegia, adult onset v3.7 PRNP Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Hereditary spastic paraplegia, adult onset v3.7 PRNP Sarah Leigh Gene: prnp has been classified as Amber List (Moderate Evidence).
Hereditary spastic paraplegia, adult onset v3.6 PRNP Sarah Leigh Publications for gene: PRNP were set to 30240140; 8250529; 34746379; 28195350; 16227536; 19228673
Hereditary spastic paraplegia, adult onset v3.5 PRNP Sarah Leigh Tag Q3_23_promote_green tag was added to gene: PRNP.
Hereditary spastic paraplegia, adult onset v3.5 PRNP Sarah Leigh Publications for gene: PRNP were set to 30240140; 8250529; 34746379; 28195350
Congenital myopathy v4.29 UNC45B Eleanor Williams commented on gene: UNC45B
Congenital myopathy v4.29 UNC45B Eleanor Williams Tag to_be_confirmed_NHSE was removed from gene: UNC45B.
Congenital myopathy v4.29 KY Eleanor Williams changed review comment from: Removed the to_be_confirmed_NHSE tag because this gene has been re-reviewed by an NHSE clinician Anna Sarkozy. Tag added in March 2022, re-reviewed in Nov 2022, removed June 2023.; to: Removed the to_be_confirmed_NHSE tag because this gene has been re-reviewed by an NHSE clinician Anna Sarkozy and so should be included in the next data review. Tag added in March 2022, re-reviewed in Nov 2022, removed June 2023.
Congenital myopathy v4.29 KY Eleanor Williams changed review comment from: Removed the to_be_confirmed_NHSE tag because this gene has been re-reviewed by an NHSE clinician.; to: Removed the to_be_confirmed_NHSE tag because this gene has been re-reviewed by an NHSE clinician Anna Sarkozy. Tag added in March 2022, re-reviewed in Nov 2022, removed June 2023.
Congenital myopathy v4.29 KY Eleanor Williams commented on gene: KY
Congenital myopathy v4.29 KY Eleanor Williams Tag to_be_confirmed_NHSE was removed from gene: KY.
Hereditary spastic paraplegia, adult onset v3.4 PRNP Sarah Leigh Phenotypes for gene: PRNP were changed from HSP; Gerstmann–Sträussler–Scheinker disease to Gerstmann-Straussler disease, OMIM: 137440
Severe microcephaly v4.25 GRM7 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: GRM7.
Severe microcephaly v4.25 GRM7 Achchuthan Shanmugasundram Classified gene: GRM7 as Amber List (moderate evidence)
Severe microcephaly v4.25 GRM7 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (three unrelated cases with severe microcephaly) for this gene to be promoted to GREEN rating at the next GMS review.
Severe microcephaly v4.25 GRM7 Achchuthan Shanmugasundram Gene: grm7 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v4.24 GRM7 Achchuthan Shanmugasundram Publications for gene: GRM7 were set to 2248644; 32286009
Severe microcephaly v4.23 GRM7 Achchuthan Shanmugasundram edited their review of gene: GRM7: Changed publications to: 32286009
Severe microcephaly v4.23 GRM7 Achchuthan Shanmugasundram changed review comment from: PMID:32286009 reported eleven individuals from six unrelated families identified with three different biallelic variants and presenting with a neurodevelopmental disorder comprising severe to profound global developmental delays, intellectual disability, seizures, hypotonia, microcephaly and brain abnormalities. This is also supported by functional evidence from knockout mouse models, where absence of metabotropic glutamate receptor 7 alters the phenotypes within the domains of social behavior, associative learning, motor function, epilepsy and sleep (PMID:32248644).

This gene has also been associated with relevant phenotypes in both OMIM (MIM #618922) and in Gene2Phenotype (with 'strong' rating in the DD panel).
Sources: Literature; to: PMID:32286009 reported eleven individuals from six unrelated families identified with three different biallelic variants and presenting with a neurodevelopmental disorder comprising severe to profound global developmental delays, intellectual disability, seizures, hypotonia, microcephaly and brain abnormalities. Head circumference measurements at time of last visit were available in eight individuals (from six families) and were consistent with microcephaly (−3.8 to −2.7 SD from mean for age). Of these four individuals from three families had severe microcephaly (head circumference beyond 3 SD from mean for age).

This gene has also been associated with relevant phenotypes in both OMIM (MIM #618922) and in Gene2Phenotype (with 'strong' rating in the DD panel).
Sources: Literature
Severe microcephaly v4.23 GRM7 Achchuthan Shanmugasundram edited their review of gene: GRM7: Changed publications to: 32248644, 32286009
Intellectual disability v5.185 GRM7 Achchuthan Shanmugasundram Classified gene: GRM7 as Amber List (moderate evidence)
Intellectual disability v5.185 GRM7 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (six unrelated cases and supporting mouse model) for this gene to be promoted to GREEN rating at the next GMS review.
Intellectual disability v5.185 GRM7 Achchuthan Shanmugasundram Gene: grm7 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.184 GRM7 Achchuthan Shanmugasundram Publications for gene: GRM7 were set to 32248644; 32286009
Intellectual disability v5.184 GRM7 Achchuthan Shanmugasundram edited their review of gene: GRM7: Changed publications to: 32248644, 32286009
Intellectual disability v5.184 GRM7 Achchuthan Shanmugasundram Publications for gene: GRM7 were set to 32248644; 32286009
Intellectual disability v5.184 GRM7 Achchuthan Shanmugasundram Publications for gene: GRM7 were set to 2248644; 32286009
Intellectual disability v5.183 GRM7 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: GRM7.
Severe microcephaly v4.23 GRM7 Achchuthan Shanmugasundram gene: GRM7 was added
gene: GRM7 was added to Severe microcephaly. Sources: Literature
Mode of inheritance for gene: GRM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GRM7 were set to 2248644; 32286009
Phenotypes for gene: GRM7 were set to Neurodevelopmental disorder with seizures, hypotonia, and brain abnormalities, OMIM:618922
Review for gene: GRM7 was set to GREEN
Added comment: PMID:32286009 reported eleven individuals from six unrelated families identified with three different biallelic variants and presenting with a neurodevelopmental disorder comprising severe to profound global developmental delays, intellectual disability, seizures, hypotonia, microcephaly and brain abnormalities. This is also supported by functional evidence from knockout mouse models, where absence of metabotropic glutamate receptor 7 alters the phenotypes within the domains of social behavior, associative learning, motor function, epilepsy and sleep (PMID:32248644).

This gene has also been associated with relevant phenotypes in both OMIM (MIM #618922) and in Gene2Phenotype (with 'strong' rating in the DD panel).
Sources: Literature
Intellectual disability v5.183 GRM7 Achchuthan Shanmugasundram gene: GRM7 was added
gene: GRM7 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: GRM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GRM7 were set to 2248644; 32286009
Phenotypes for gene: GRM7 were set to Neurodevelopmental disorder with seizures, hypotonia, and brain abnormalities, OMIM:618922
Review for gene: GRM7 was set to GREEN
Added comment: PMID:32286009 reported eleven individuals from six unrelated families identified with three different biallelic variants and presenting with a neurodevelopmental disorder comprising severe to profound global developmental delays, intellectual disability, seizures, hypotonia, microcephaly and brain abnormalities. This is also supported by functional evidence from knockout mouse models, where absence of metabotropic glutamate receptor 7 alters the phenotypes within the domains of social behavior, associative learning, motor function, epilepsy and sleep (PMID:32248644).

This gene has also been associated with relevant phenotypes in both OMIM (MIM #618922) and in Gene2Phenotype (with 'strong' rating in the DD panel).
Sources: Literature
Early onset or syndromic epilepsy v4.48 GRM7 Achchuthan Shanmugasundram changed review comment from: PMID:32286009 reported eleven individuals from six unrelated families identified with three different biallelic variants and presenting with a neurodevelopmental disorder comprising global developmental delay/ intellectual impairment, seizures, hypotonia, microcephaly and brain abnormalities. This is also supported by functional evidence from knockout mouse models, where absence of metabotropic glutamate receptor 7 alters the phenotypes within the domains of social behavior, associative learning, motor function, epilepsy and sleep (PMID:32248644).

This gene has also been associated with relevant phenotypes in both OMIM (MIM #618922) and in Gene2Phenotype (with 'strong' rating in the DD panel).; to: PMID:32286009 reported eleven individuals from six unrelated families identified with three different biallelic variants and presenting with a neurodevelopmental disorder comprising severe to profound global developmental delays, intellectual disability, seizures, hypotonia, microcephaly and brain abnormalities. This is also supported by functional evidence from knockout mouse models, where absence of metabotropic glutamate receptor 7 alters the phenotypes within the domains of social behavior, associative learning, motor function, epilepsy and sleep (PMID:32248644).

This gene has also been associated with relevant phenotypes in both OMIM (MIM #618922) and in Gene2Phenotype (with 'strong' rating in the DD panel).
Early onset or syndromic epilepsy v4.48 GRM7 Achchuthan Shanmugasundram changed review comment from: PMID:32286009 reported eleven individuals from six unrelated families identified with three different biallelic variants and presenting with a neurodevelopmentakl disorder comprising global developmental delay/ intellectual impairment, seizures, hypotonia, microcephaly and brain abnormalities. This is also supported by functional evidence from knockout mouse models, where absence of metabotropic glutamate receptor 7 alters the phenotypes within the domains of social behavior, associative learning, motor function, epilepsy and sleep (PMID:32248644).

This gene has also been associated with relevant phenotypes in both OMIM (MIM #618922) and in Gene2Phenotype (with 'strong' rating in the DD panel).; to: PMID:32286009 reported eleven individuals from six unrelated families identified with three different biallelic variants and presenting with a neurodevelopmental disorder comprising global developmental delay/ intellectual impairment, seizures, hypotonia, microcephaly and brain abnormalities. This is also supported by functional evidence from knockout mouse models, where absence of metabotropic glutamate receptor 7 alters the phenotypes within the domains of social behavior, associative learning, motor function, epilepsy and sleep (PMID:32248644).

This gene has also been associated with relevant phenotypes in both OMIM (MIM #618922) and in Gene2Phenotype (with 'strong' rating in the DD panel).
Early onset or syndromic epilepsy v4.48 GRM7 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: GRM7.
Early onset or syndromic epilepsy v4.48 GRM7 Achchuthan Shanmugasundram Classified gene: GRM7 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.48 GRM7 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (6 unrelated cases and supporting mouse model) for this gene to be promoted to GREEN at the next major update.
Early onset or syndromic epilepsy v4.48 GRM7 Achchuthan Shanmugasundram Gene: grm7 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.47 GRM7 Achchuthan Shanmugasundram Phenotypes for gene: GRM7 were changed from Epilepsy, microcephaly, developmental delay to Neurodevelopmental disorder with seizures, hypotonia, and brain abnormalities, OMIM:618922
Early onset or syndromic epilepsy v4.46 GRM7 Achchuthan Shanmugasundram reviewed gene: GRM7: Rating: GREEN; Mode of pathogenicity: None; Publications: 32248644, 32286009; Phenotypes: Neurodevelopmental disorder with seizures, hypotonia, and brain abnormalities, OMIM:618922; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary spastic paraplegia, childhood onset v4.10 CCDC82 Achchuthan Shanmugasundram Classified gene: CCDC82 as Amber List (moderate evidence)
Hereditary spastic paraplegia, childhood onset v4.10 CCDC82 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are two unrelated cases and hence this gene should be rated AMBER.
Hereditary spastic paraplegia, childhood onset v4.10 CCDC82 Achchuthan Shanmugasundram Gene: ccdc82 has been classified as Amber List (Moderate Evidence).
Hereditary spastic paraplegia, childhood onset v4.9 CCDC82 Achchuthan Shanmugasundram gene: CCDC82 was added
gene: CCDC82 was added to Childhood onset hereditary spastic paraplegia. Sources: Literature
Mode of inheritance for gene: CCDC82 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC82 were set to 35118659; 35373332
Phenotypes for gene: CCDC82 were set to neurodevelopmental disorder, MONDO:0700092; hereditary spastic paraplegia, MONDO:0019064
Review for gene: CCDC82 was set to AMBER
Added comment: PMID: 35118659 reported two siblings presenting with global global developmental delay (last evaluation at 4 years and 9 months) and spasticity. They also had a common history of infantile spasms with the elder developing GTC convulsions with spontaneous resolution and both presented with microcephaly (<-2 and <-3SD). They harboured homozygous variant c.535C>T ( p.Arg179Ter).

PMID: 35373332 reported a 21 years old male who presented with features included short stature, intellectual disability, spastic paraparesis (at the age of 3 years). Gelastic seizures were suspected but not confirmed (repeated normal EEGs). This patient harboured a homozygous frameshift CCDC82 variant c.183del (p.Phe61Leufs*27) and the parents were heterozygous carriers. There was another homozygous variant, albeit classified as VUS and not thought to fit the clinical presentation.
Sources: Literature
Intellectual disability v5.182 CCDC82 Achchuthan Shanmugasundram changed review comment from: As reviewed by Konstantinos Varvagiannis, there is more than three unrelated cases with biallelic variants in CCDC82 presenting with a neurodevelopmental disorder comprising intellectual disability/ global developmental delay. Hence, this gene should be rated GREEN at the next GMS review.; to: As reviewed by Konstantinos Varvagiannis, there are more than three unrelated cases with biallelic variants in CCDC82 presenting with a neurodevelopmental disorder comprising intellectual disability/ global developmental delay. Hence, this gene should be rated GREEN at the next GMS review.
Intellectual disability v5.182 CCDC82 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: CCDC82.
Intellectual disability v5.182 CCDC82 Achchuthan Shanmugasundram Classified gene: CCDC82 as Amber List (moderate evidence)
Intellectual disability v5.182 CCDC82 Achchuthan Shanmugasundram Gene: ccdc82 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.182 CCDC82 Achchuthan Shanmugasundram Classified gene: CCDC82 as Amber List (moderate evidence)
Intellectual disability v5.182 CCDC82 Achchuthan Shanmugasundram Gene: ccdc82 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.181 CCDC82 Achchuthan Shanmugasundram Phenotypes for gene: CCDC82 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.182 CCDC82 Achchuthan Shanmugasundram Phenotypes for gene: CCDC82 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.181 CCDC82 Achchuthan Shanmugasundram Phenotypes for gene: CCDC82 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.181 CCDC82 Achchuthan Shanmugasundram Phenotypes for gene: CCDC82 were changed from Global developmental delay; Intellectual disability; Spastic paraparesis to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.180 CCDC82 Achchuthan Shanmugasundram commented on gene: CCDC82: As reviewed by Konstantinos Varvagiannis, there is more than three unrelated cases with biallelic variants in CCDC82 presenting with a neurodevelopmental disorder comprising intellectual disability/ global developmental delay. Hence, this gene should be rated GREEN at the next GMS review.
Intellectual disability v5.180 CCDC82 Achchuthan Shanmugasundram reviewed gene: CCDC82: Rating: GREEN; Mode of pathogenicity: None; Publications: 27457812, 28397838, 35118659, 35373332; Phenotypes: neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.180 FLNA Sarah Leigh edited their review of gene: FLNA: Changed rating: RED
Intellectual disability v5.180 FLNA Sarah Leigh reviewed gene: FLNA: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v5.180 FLNA Sarah Leigh Tag Q2_23_demote_red tag was added to gene: FLNA.
Intellectual disability v5.180 FLNA Sarah Leigh Publications for gene: FLNA were set to
Intellectual disability v5.179 UBE3C Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.179 UBE3C Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: UBE3C.
Intellectual disability v5.179 UBE3C Achchuthan Shanmugasundram Classified gene: UBE3C as Amber List (moderate evidence)
Intellectual disability v5.179 UBE3C Achchuthan Shanmugasundram Added comment: Comment on list classification: There are two unrelated cases associating biallelic variants in UBE3C gene with intellectual disability. Hence, this gene should be rated AMBER.
Intellectual disability v5.179 UBE3C Achchuthan Shanmugasundram Gene: ube3c has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.179 UBE3C Achchuthan Shanmugasundram Classified gene: UBE3C as Amber List (moderate evidence)
Intellectual disability v5.179 UBE3C Achchuthan Shanmugasundram Added comment: Comment on list classification: There are two unrelated cases associating biallelic variants in UBE3C gene with intellectual disability. Hence, this gene should be rated AMBER.
Intellectual disability v5.179 UBE3C Achchuthan Shanmugasundram Gene: ube3c has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.178 UBE3C Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: UBE3C.
Intellectual disability v5.178 UBE3C Achchuthan Shanmugasundram gene: UBE3C was added
gene: UBE3C was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: UBE3C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UBE3C were set to 36401616
Phenotypes for gene: UBE3C were set to Neurodevelopmental disorder with absent speech and movement and behavioral abnormalities, OMIM:620270
Review for gene: UBE3C was set to AMBER
Added comment: PMID:36401616 reported three patients from two unrelated families with homozygous variants in UBE3C gene and presenting with syndromic neurodevelopmental, seizure, and movement disorders and neurobehavioral phenotypes. All three patients had severe intellectual disability. The RNA studies in some patients with LoF variants provided evidence for the LoF effect.
Sources: Literature
Intellectual disability v5.177 HECTD4 Achchuthan Shanmugasundram Classified gene: HECTD4 as Amber List (moderate evidence)
Intellectual disability v5.177 HECTD4 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (five unrelated families) for this gene to be promoted to GREEN rating at the next major update.
Intellectual disability v5.177 HECTD4 Achchuthan Shanmugasundram Gene: hectd4 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.177 HECTD4 Achchuthan Shanmugasundram Classified gene: HECTD4 as Amber List (moderate evidence)
Intellectual disability v5.177 HECTD4 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (five unrelated families) for this gene to be promoted to GREEN rating at the next major update.
Intellectual disability v5.177 HECTD4 Achchuthan Shanmugasundram Gene: hectd4 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.177 HECTD4 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.177 HECTD4 Achchuthan Shanmugasundram Classified gene: HECTD4 as Amber List (moderate evidence)
Intellectual disability v5.177 HECTD4 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (five unrelated families) for this gene to be promoted to GREEN rating at the next major update.
Intellectual disability v5.177 HECTD4 Achchuthan Shanmugasundram Gene: hectd4 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.176 HECTD4 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: HECTD4.
Intellectual disability v5.176 HECTD4 Achchuthan Shanmugasundram Classified gene: HECTD4 as Amber List (moderate evidence)
Intellectual disability v5.176 HECTD4 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (five unrelated families) for this gene to be promoted to GREEN rating at the next major update.
Intellectual disability v5.176 HECTD4 Achchuthan Shanmugasundram Gene: hectd4 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.175 HECTD4 Achchuthan Shanmugasundram gene: HECTD4 was added
gene: HECTD4 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: HECTD4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HECTD4 were set to 36401616
Phenotypes for gene: HECTD4 were set to Neurodevelopmental disorder with seizures, spasticity, and complete or partial agenesis of the corpus callosum, OMIM:620250
Review for gene: HECTD4 was set to GREEN
Added comment: PMID:36401616 reported seven patients from five unrelated families with either homozygous (3 families) or compound heterozygous variants (2 families) in HECTD4 gene and presenting with syndromic neurodevelopmental, seizure, and movement disorders and neurobehavioral phenotypes. All seven patients had severe (4 cases) or moderate (3 cases) intellectual disability.
Sources: Literature
Severe microcephaly v4.22 FILIP1 Achchuthan Shanmugasundram Tag watchlist tag was added to gene: FILIP1.
Severe microcephaly v4.22 FILIP1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There are two unrelated cases reported with severe microcephaly and three additional cases with microcephaly. Hence, this gene should be rated amber in this panel with the current evidence. 'watchlist' tag has been added to review the rating in the future new evidence.; to: Comment on list classification: There are two unrelated cases reported with severe microcephaly and three additional cases with microcephaly. Hence, this gene should be rated amber in this panel with the current evidence. The 'watchlist' tag has been added to review the rating in the future with any new evidence.
Severe microcephaly v4.22 FILIP1 Achchuthan Shanmugasundram Classified gene: FILIP1 as Amber List (moderate evidence)
Severe microcephaly v4.22 FILIP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are two unrelated cases reported with severe microcephaly and three additional cases with microcephaly. Hence, this gene should be rated amber in this panel with the current evidence. 'watchlist' tag has been added to review the rating in the future new evidence.
Severe microcephaly v4.22 FILIP1 Achchuthan Shanmugasundram Gene: filip1 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v4.21 FILIP1 Achchuthan Shanmugasundram gene: FILIP1 was added
gene: FILIP1 was added to Severe microcephaly. Sources: Literature
Mode of inheritance for gene: FILIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FILIP1 were set to 36943452; 37163662
Phenotypes for gene: FILIP1 were set to microcephaly, MONDO:0001149
Review for gene: FILIP1 was set to AMBER
Added comment: PMID:36943452 reported five individuals from three unrelated families with three different biallelic variants in FILIP1 gene (including the variant reported in the patient from PMID:36344539) and presenting with an overlapping phenotype with congenital contractures affecting shoulder, elbow, hand, hip, knee and foot as well as scoliosis, reduced palmar and plantar skin folds, microcephaly and facial dysmorphism. Of these five patients, two unrelated patients had severe microcephaly (head circumference beyond 3 SD below the mean for age) and one patient from the family with three patients also had microcephaly (head circumference beyond 2 SD below the mean for age).

PMID:37163662 reported five individuals from four unrelated families with four different biallelic variants in FILIP1 gene. The main symptoms in childhood included delayed motor milestones (all four families), delayed speech development (three families), intellectual disability (three families), contractures (2 families), clubfeet (2 families) and microcephaly (2 families). One of these cases only had borderline microcephaly (3rd percentile) and the other had OFC below 3rd percentile.
Sources: Literature
Dystonia, chorea or related movement disorder, childhood onset v3.11 NUP54 Achchuthan Shanmugasundram changed review comment from: PMID:36333996 reported three unrelated patients with early-onset dystonia with striatal lesions identified with biallelic variants in NUP54 gene. One patient (patient A) had homozygous variant c.1073T>G (p.Ile358Ser), while other two patients had compound heterozygous variants (patient B: c.1073T>G (p.Ile358Ser) & c.1126A>G (p.Lys376Glu); patient C: c.1410_1412del (p.Gln471del) and two missense variants c.1414G>A (p.Glu472Lys) & c.1420C>T (p.Leu474Phe)).

The age of onset was between 12 months and five years and all had progressive neurological deterioration with dystonia, ataxia, dysarthria, dysphagia, hypotonia.

This gene has been associated with relevant phenotypes in Gene2Phenotype (NUP54-related early-onset dystonia with striatal lesions with 'moderate' rating in the DD panel), but not in OMIM.
Sources: Literature; to: PMID:36333996 reported three unrelated patients with early-onset dystonia with striatal lesions identified with biallelic variants in NUP54 gene. One patient (patient A) had homozygous variant c.1073T>G (p.Ile358Ser), while other two patients had compound heterozygous variants (patient B: c.1073T>G (p.Ile358Ser) & c.1126A>G (p.Lys376Glu); patient C: c.1410_1412del (p.Gln471del) and two missense variants c.1414G>A (p.Glu472Lys) & c.1420C>T (p.Leu474Phe)).

The age of onset was between 12 months and five years and all had progressive neurological deterioration with dystonia, ataxia, dysarthria, dysphagia, hypotonia.

Western blots showed reduced expression of NUP54 and its interaction partners NUP62/NUP58 in patient fibroblasts.

This gene has been associated with relevant phenotypes in Gene2Phenotype (NUP54-related early-onset dystonia with striatal lesions with 'moderate' rating in the DD panel), but not in OMIM.
Sources: Literature
Dystonia, chorea or related movement disorder, childhood onset v3.11 NUP54 Achchuthan Shanmugasundram Classified gene: NUP54 as Amber List (moderate evidence)
Dystonia, chorea or related movement disorder, childhood onset v3.11 NUP54 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (3 unrelated cases) for rating this gene as GREEN in the next GMS review.
Dystonia, chorea or related movement disorder, childhood onset v3.11 NUP54 Achchuthan Shanmugasundram Gene: nup54 has been classified as Amber List (Moderate Evidence).
Dystonia, chorea or related movement disorder, childhood onset v3.10 NUP54 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: NUP54.
Dystonia, chorea or related movement disorder, childhood onset v3.10 NUP54 Achchuthan Shanmugasundram gene: NUP54 was added
gene: NUP54 was added to Childhood onset dystonia, chorea or related movement disorder. Sources: Literature
Mode of inheritance for gene: NUP54 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP54 were set to 36333996
Phenotypes for gene: NUP54 were set to Early-onset dystonia
Review for gene: NUP54 was set to GREEN
Added comment: PMID:36333996 reported three unrelated patients with early-onset dystonia with striatal lesions identified with biallelic variants in NUP54 gene. One patient (patient A) had homozygous variant c.1073T>G (p.Ile358Ser), while other two patients had compound heterozygous variants (patient B: c.1073T>G (p.Ile358Ser) & c.1126A>G (p.Lys376Glu); patient C: c.1410_1412del (p.Gln471del) and two missense variants c.1414G>A (p.Glu472Lys) & c.1420C>T (p.Leu474Phe)).

The age of onset was between 12 months and five years and all had progressive neurological deterioration with dystonia, ataxia, dysarthria, dysphagia, hypotonia.

This gene has been associated with relevant phenotypes in Gene2Phenotype (NUP54-related early-onset dystonia with striatal lesions with 'moderate' rating in the DD panel), but not in OMIM.
Sources: Literature
Ectodermal dysplasia v3.3 TUFT1 Achchuthan Shanmugasundram Classified gene: TUFT1 as Amber List (moderate evidence)
Ectodermal dysplasia v3.3 TUFT1 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER despite having three unrelated cases, as the variant found in two families is a founder variant in the Irish population.
Ectodermal dysplasia v3.3 TUFT1 Achchuthan Shanmugasundram Gene: tuft1 has been classified as Amber List (Moderate Evidence).
Ectodermal dysplasia v3.2 TUFT1 Achchuthan Shanmugasundram gene: TUFT1 was added
gene: TUFT1 was added to Ectodermal dysplasia. Sources: Literature
Mode of inheritance for gene: TUFT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TUFT1 were set to 36689522
Phenotypes for gene: TUFT1 were set to ectodermal dysplasia syndrome, MONDO:0019287
Review for gene: TUFT1 was set to AMBER
Added comment: PMID:36689522 reported nine individuals from three different families with biallelic variants in TUFT1 gene and presenting with woolly hair and skin fragility. One donor splice-site variant, c.60+1G>A, was present in two families, while a frameshift variant, p.Gln189Asnfs*49, was found in the third family. Haplotype analysis showed the c.60+1G>A variant is a founder variant in the Irish population. This is also supported by functional studies, mainly expression studies.

This gene has not yet been associated with any phenotypes in OMIM or in Gene2Phenotype.
Sources: Literature
Lysosomal storage disorder v3.1 VPS16 Sarah Leigh changed review comment from: The rating of this gene has been updated following NHS Genomic Medicine Serviceapproval.; to: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Dystonia, chorea or related movement disorder, adult onset v3.2 VPS16 Sarah Leigh changed review comment from: The rating of this gene has been updated followingNHS Genomic Medicine Serviceapproval.; to: The rating of this gene has been updated following NHS Genomic Medicine Serviceapproval.
Severe microcephaly v4.20 TRA2B Achchuthan Shanmugasundram Classified gene: TRA2B as Amber List (moderate evidence)
Severe microcephaly v4.20 TRA2B Achchuthan Shanmugasundram Added comment: Comment on list classification: There are only two unrelated cases with severe microcephaly. Hence, this gene should be rated AMBER.
Severe microcephaly v4.20 TRA2B Achchuthan Shanmugasundram Gene: tra2b has been classified as Amber List (Moderate Evidence).
Severe microcephaly v4.19 TRA2B Achchuthan Shanmugasundram Phenotypes for gene: TRA2B were changed from neurodevelopmental disorder, MONDO:0700092; epilepsy, MONDO:0005027 to neurodevelopmental disorder, MONDO:0700092; microcephaly, MONDO:0001149
Severe microcephaly v4.18 TRA2B Achchuthan Shanmugasundram changed review comment from: This gene has already been associated with phenotypes in Gene2Phenotype (with 'moderate' rating in the DD panel), but not in OMIM.
Sources: Literature; to: PMID:36549593 reported 12 individuals from 11 unrelated families identified with 11 different heterozygous variants in TRA2B gene. The variants arose de novo in 10 families, while the variant was inherited from father to son in one family. 6 variants were expected to disrupt the translation start site in exon 1 (start-loss variants), 3 were expected to disrupt the splicing process at the exon 2/3 boundary (splice-affecting variants), and the remaining 2 were expected to produce a premature stop codon (truncating variants).

These patients presented with a neurodevelopmental disorder comprising developmental delay/ intellectual disability (in all patients), axial or global hypotonia (10 patients), delayed motor milestones (all patients), behavioural issues (8 patients), speech impairment (9 patients), epilepsy (7 patients, initial presentation as infantile spasms in 6 and unclassified epileptic encephalopathy in 1), brain abnormalities (10 patients) and microcephaly (5 patients). Of 5 unrelated cases with microcephaly, only two cases had severe microcephaly (head circumference beyond 3 standard deviations below the mean for the age).

In addition, functional studies in mice showed that heterozygous knockout mice developed normal, while complete knockout mice cannot develop embryonically.

This gene has already been associated with phenotypes in Gene2Phenotype (with 'moderate' rating in the DD panel), but not in OMIM.
Sources: Literature
Severe microcephaly v4.18 TRA2B Achchuthan Shanmugasundram edited their review of gene: TRA2B: Changed rating: AMBER; Changed phenotypes to: neurodevelopmental disorder, MONDO:0700092, microcephaly, MONDO:0001149
Intellectual disability v5.174 TRA2B Achchuthan Shanmugasundram Classified gene: TRA2B as Amber List (moderate evidence)
Intellectual disability v5.174 TRA2B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (11 unrelated cases) for this gene to be rated GREEN at the next GMS review.
Intellectual disability v5.174 TRA2B Achchuthan Shanmugasundram Gene: tra2b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.174 TRA2B Achchuthan Shanmugasundram Classified gene: TRA2B as Amber List (moderate evidence)
Intellectual disability v5.174 TRA2B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (11 unrelated cases) for this gene to be rated GREEN at the next GMS review.
Intellectual disability v5.174 TRA2B Achchuthan Shanmugasundram Gene: tra2b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.174 TRA2B Achchuthan Shanmugasundram Classified gene: TRA2B as Amber List (moderate evidence)
Intellectual disability v5.174 TRA2B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (11 unrelated cases) for this gene to be rated GREEN at the next GMS review.
Intellectual disability v5.174 TRA2B Achchuthan Shanmugasundram Gene: tra2b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.174 TRA2B Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.174 TRA2B Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.174 TRA2B Achchuthan Shanmugasundram Classified gene: TRA2B as Amber List (moderate evidence)
Intellectual disability v5.174 TRA2B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (11 unrelated cases) for this gene to be rated GREEN at the next GMS review.
Intellectual disability v5.174 TRA2B Achchuthan Shanmugasundram Gene: tra2b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.173 TRA2B Achchuthan Shanmugasundram Classified gene: TRA2B as Amber List (moderate evidence)
Intellectual disability v5.173 TRA2B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (11 unrelated cases) for this gene to be rated GREEN at the next GMS review.
Intellectual disability v5.173 TRA2B Achchuthan Shanmugasundram Gene: tra2b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.173 TRA2B Achchuthan Shanmugasundram Classified gene: TRA2B as Amber List (moderate evidence)
Intellectual disability v5.173 TRA2B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (11 unrelated cases) for this gene to be rated GREEN at the next GMS review.
Intellectual disability v5.173 TRA2B Achchuthan Shanmugasundram Gene: tra2b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.172 TRA2B Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: TRA2B.
Intellectual disability v5.172 TRA2B Achchuthan Shanmugasundram Phenotypes for gene: TRA2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.172 TRA2B Achchuthan Shanmugasundram Phenotypes for gene: TRA2B were changed from neurodevelopmental disorder, MONDO:0700092; epilepsy, MONDO:0005027 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.171 TRA2B Achchuthan Shanmugasundram edited their review of gene: TRA2B: Changed phenotypes to: neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071
Intellectual disability v5.171 TRA2B Achchuthan Shanmugasundram changed review comment from: This gene has already been associated with phenotypes in Gene2Phenotype (with 'moderate' rating in the DD panel), but not in OMIM.
Sources: Literature; to: PMID:36549593 reported 12 individuals from 11 unrelated families identified with 11 different heterozygous variants in TRA2B gene. The variants arose de novo in 10 families, while the variant was inherited from father to son in one family. 6 variants were expected to disrupt the translation start site in exon 1 (start-loss variants), 3 were expected to disrupt the splicing process at the exon 2/3 boundary (splice-affecting variants), and the remaining 2 were expected to produce a premature stop codon (truncating variants).

These patients presented with a neurodevelopmental disorder comprising developmental delay/ intellectual disability (in all patients), axial or global hypotonia (10 patients), delayed motor milestones (all patients), behavioural issues (8 patients), speech impairment (9 patients), epilepsy (7 patients, initial presentation as infantile spasms in 6 and unclassified epileptic encephalopathy in 1), brain abnormalities (10 patients) and microcephaly (5 patients). The degree of ID was severe to profound for 6 individuals, moderate to severe for 2 and mild to moderate for 3.

In addition, functional studies in mice showed that heterozygous knockout mice developed normal, while complete knockout mice cannot develop embryonically.

This gene has already been associated with phenotypes in Gene2Phenotype (with 'moderate' rating in the DD panel), but not in OMIM.
Sources: Literature
Early onset or syndromic epilepsy v4.46 TRA2B Achchuthan Shanmugasundram Classified gene: TRA2B as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.46 TRA2B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (7 unrelated cases) for rating this gene as GREEN in the next GMS review.
Early onset or syndromic epilepsy v4.46 TRA2B Achchuthan Shanmugasundram Gene: tra2b has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.45 TRA2B Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: TRA2B.
Early onset or syndromic epilepsy v4.45 TRA2B Achchuthan Shanmugasundram changed review comment from: This gene has already been associated with phenotypes in Gene2Phenotype (with 'moderate' rating in the DD panel), but not in OMIM.
Sources: Literature; to: PMID:36549593 reported 12 individuals from 11 unrelated families identified with 11 different heterozygous variants in TRA2B gene. The variants arose de novo in 10 families, while the variant was inherited from father to son in one family. 6 variants were expected to disrupt the translation start site in exon 1 (start-loss variants), 3 were expected to disrupt the splicing process at the exon 2/3 boundary (splice-affecting variants), and the remaining 2 were expected to produce a premature stop codon (truncating variants).

These patients presented with a neurodevelopmental disorder comprising developmental delay/ intellectual disability (in all patients), axial or global hypotonia (10 patients), delayed motor milestones (all patients), behavioural issues (8 patients), speech impairment (9 patients), epilepsy (7 patients, initial presentation as infantile spasms in 6 and unclassified epileptic encephalopathy in 1), brain abnormalities (10 patients) and microcephaly (5 patients).

In addition, functional studies in mice showed that heterozygous knockout mice developed normal, while complete knockout mice cannot develop embryonically.

This gene has already been associated with phenotypes in Gene2Phenotype (with 'moderate' rating in the DD panel), but not in OMIM.
Sources: Literature
Severe microcephaly v4.18 TRA2B Achchuthan Shanmugasundram gene: TRA2B was added
gene: TRA2B was added to Severe microcephaly. Sources: Literature
Mode of inheritance for gene: TRA2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRA2B were set to 36549593
Phenotypes for gene: TRA2B were set to neurodevelopmental disorder, MONDO:0700092; epilepsy, MONDO:0005027
Review for gene: TRA2B was set to GREEN
Added comment: This gene has already been associated with phenotypes in Gene2Phenotype (with 'moderate' rating in the DD panel), but not in OMIM.
Sources: Literature
Intellectual disability v5.171 TRA2B Achchuthan Shanmugasundram gene: TRA2B was added
gene: TRA2B was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: TRA2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRA2B were set to 36549593
Phenotypes for gene: TRA2B were set to neurodevelopmental disorder, MONDO:0700092; epilepsy, MONDO:0005027
Review for gene: TRA2B was set to GREEN
Added comment: This gene has already been associated with phenotypes in Gene2Phenotype (with 'moderate' rating in the DD panel), but not in OMIM.
Sources: Literature
Early onset or syndromic epilepsy v4.45 TRA2B Achchuthan Shanmugasundram gene: TRA2B was added
gene: TRA2B was added to Early onset or syndromic epilepsy. Sources: Literature
Mode of inheritance for gene: TRA2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRA2B were set to 36549593
Phenotypes for gene: TRA2B were set to neurodevelopmental disorder, MONDO:0700092; epilepsy, MONDO:0005027
Review for gene: TRA2B was set to GREEN
Added comment: This gene has already been associated with phenotypes in Gene2Phenotype (with 'moderate' rating in the DD panel), but not in OMIM.
Sources: Literature
Mitochondrial disorder with complex II deficiency v2.6 SDHA Achchuthan Shanmugasundram Deleted their comment
Mitochondrial disorder with complex II deficiency v2.6 SDHA Achchuthan Shanmugasundram commented on gene: SDHA: Test
Mitochondrial disorder with complex II deficiency v2.5 SDHB Achchuthan Shanmugasundram Deleted their comment
Mitochondrial disorder with complex II deficiency v2.5 SDHA Achchuthan Shanmugasundram Deleted their comment
Mitochondrial disorder with complex II deficiency v2.5 SDHB Achchuthan Shanmugasundram commented on gene: SDHB: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Mitochondrial disorder with complex II deficiency v2.5 SDHA Achchuthan Shanmugasundram commented on gene: SDHA: The mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Intellectual disability v5.170 ZMYND8 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.170 ZMYND8 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.170 ZMYND8 Achchuthan Shanmugasundram Deleted their comment
White matter disorders and cerebral calcification - childhood onset v3.14 CLDN5 Achchuthan Shanmugasundram Classified gene: CLDN5 as Amber List (moderate evidence)
White matter disorders and cerebral calcification - childhood onset v3.14 CLDN5 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be rated GREEN at the next GMS review.
White matter disorders and cerebral calcification - childhood onset v3.14 CLDN5 Achchuthan Shanmugasundram Gene: cldn5 has been classified as Amber List (Moderate Evidence).
White matter disorders and cerebral calcification - childhood onset v3.13 CLDN5 Achchuthan Shanmugasundram changed review comment from: PMID: 36477332 identified de novo heterozygous missense variants in CLDN5 in fifteen unrelated patients who presented with a shared constellation of features including developmental delay, seizures (primarily infantile onset focal epilepsy), microcephaly and a recognizable pattern of pontine atrophy and brain calcifications.
Sources: Literature; to: PMID:36477332 reported the identification of de novo heterozygous missense variants in CLDN5 in 15 unrelated patients who presented with a number of clinical features including developmental delay including intellectual disability, seizures (primarily infantile onset focal epilepsy), microcephaly and a recognisable pattern of pontine atrophy and brain calcifications. All patients except one (patient 2 who had a single MRI taken at 4 days of age) showed pontine atrophy and brain calcifications from neuroimaging.

In addition, functional studies from zebrafish model also provided parallel evidence that CLDN5 variants cause a neurodevelopmental disorder involving disruption of the blood brain barrier and impaired neuronal function.

This gene has been associated with relevant phenotypes in Gene2Phenotype (CLDN5-related neurodevelopmental disorder with 'limited' rating in the DD panel), but not in OMIM.
Sources: Literature
White matter disorders and cerebral calcification - childhood onset v3.13 CLDN5 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: CLDN5.
White matter disorders and cerebral calcification - childhood onset v3.13 CLDN5 Achchuthan Shanmugasundram Phenotypes for gene: CLDN5 were changed from Brain calcifications to Brain calcifications
White matter disorders and cerebral calcification - childhood onset v3.12 CLDN5 Achchuthan Shanmugasundram Phenotypes for gene: CLDN5 were changed from Brain calcifications to Brain calcifications
White matter disorders and cerebral calcification - childhood onset v3.12 CLDN5 Achchuthan Shanmugasundram Phenotypes for gene: CLDN5 were changed from epilepsy, MONDO:0005027 to Brain calcifications
White matter disorders and cerebral calcification - childhood onset v3.11 CLDN5 Achchuthan Shanmugasundram edited their review of gene: CLDN5: Changed phenotypes to: Brain calcifications
Intellectual disability v5.170 ATG4D Dmitrijs Rots gene: ATG4D was added
gene: ATG4D was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: ATG4D was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATG4D were set to 36765070
Phenotypes for gene: ATG4D were set to neurodevelopmental disorder characterized by speech and motor impairment
Review for gene: ATG4D was set to GREEN
Added comment: Morimoto et al., described 3 cases from 2 families with ATG4D biallelic variants and provided some functional evidence.
No data about homozygous or compound heterozygous with two rare variants in ATG4D in gnomAD database.
Sources: Literature
Intellectual disability v5.170 CLDN5 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.170 CLDN5 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.170 CLDN5 Achchuthan Shanmugasundram Classified gene: CLDN5 as Amber List (moderate evidence)
Intellectual disability v5.170 CLDN5 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be rated GREEN in the next GMS review.
Intellectual disability v5.170 CLDN5 Achchuthan Shanmugasundram Gene: cldn5 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.170 CLDN5 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: CLDN5.
Intellectual disability v5.170 CLDN5 Achchuthan Shanmugasundram Classified gene: CLDN5 as Amber List (moderate evidence)
Intellectual disability v5.170 CLDN5 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be rated GREEN in the next GMS review.
Intellectual disability v5.170 CLDN5 Achchuthan Shanmugasundram Gene: cldn5 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.169 CLDN5 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.169 CLDN5 Achchuthan Shanmugasundram Classified gene: CLDN5 as Amber List (moderate evidence)
Intellectual disability v5.169 CLDN5 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be rated GREEN in the next GMS review.
Intellectual disability v5.169 CLDN5 Achchuthan Shanmugasundram Gene: cldn5 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.169 CLDN5 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.169 CLDN5 Achchuthan Shanmugasundram Classified gene: CLDN5 as Amber List (moderate evidence)
Intellectual disability v5.169 CLDN5 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be rated GREEN in the next GMS review.
Intellectual disability v5.169 CLDN5 Achchuthan Shanmugasundram Gene: cldn5 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.169 CLDN5 Achchuthan Shanmugasundram Classified gene: CLDN5 as Amber List (moderate evidence)
Intellectual disability v5.169 CLDN5 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be rated GREEN in the next GMS review.
Intellectual disability v5.169 CLDN5 Achchuthan Shanmugasundram Gene: cldn5 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.168 CLDN5 Achchuthan Shanmugasundram Phenotypes for gene: CLDN5 were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.168 CLDN5 Achchuthan Shanmugasundram Phenotypes for gene: CLDN5 were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.168 CLDN5 Achchuthan Shanmugasundram Phenotypes for gene: CLDN5 were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.167 CLDN5 Achchuthan Shanmugasundram Phenotypes for gene: CLDN5 were changed from epilepsy, MONDO:0005027 to intellectual disability, MONDO:0001071
Intellectual disability v5.166 CLDN5 Achchuthan Shanmugasundram edited their review of gene: CLDN5: Changed phenotypes to: intellectual disability, MONDO:0001071
Intellectual disability v5.166 CLDN5 Achchuthan Shanmugasundram changed review comment from: PMID: 36477332 identified de novo heterozygous missense variants in CLDN5 in fifteen unrelated patients who presented with a shared constellation of features including developmental delay, seizures (primarily infantile onset focal epilepsy), microcephaly and a recognizable pattern of pontine atrophy and brain calcifications.
Sources: Literature; to: PMID:36477332 reported the identification of de novo heterozygous missense variants in CLDN5 in 15 unrelated patients who presented with a number of clinical features including developmental delay including intellectual disability, seizures (primarily infantile onset focal epilepsy), microcephaly and a recognisable pattern of pontine atrophy and brain calcifications. All seven living patients over four years of age were reported to have intellectual disability.

In addition, functional studies from zebrafish model also provided parallel evidence that CLDN5 variants cause a neurodevelopmental disorder involving disruption of the blood brain barrier and impaired neuronal function.

This gene has been associated with relevant phenotypes in Gene2Phenotype (CLDN5-related neurodevelopmental disorder with 'limited' rating in the DD panel), but not in OMIM.
Sources: Literature
Early onset or syndromic epilepsy v4.44 CLDN5 Achchuthan Shanmugasundram changed review comment from: PMID:36477332 reported the identification of de novo heterozygous missense variants in CLDN5 in 15 unrelated patients who presented with a number of clinical features including developmental delay including intellectual disability, seizures (primarily infantile onset focal epilepsy), microcephaly and a recognisable pattern of pontine atrophy and brain calcifications. All 15 patients had seizures.

In addition, functional studies from zebrafish model also provided parallel evidence that CLDN5 variants cause a neurodevelopmental disorder involving disruption of the blood brain barrier and impaired neuronal function.

This gene has been associated with relevant phenotypes in Gene2Phenotype (CLDN5-related neurodevelopmental disorder with 'limited' rating in the DD panel), but not in OMIM.
Sources: Literature; to: PMID:36477332 reported the identification of de novo heterozygous missense variants in CLDN5 in 15 unrelated patients who presented with a number of clinical features including developmental delay including intellectual disability, seizures (primarily infantile onset focal epilepsy), microcephaly and a recognisable pattern of pontine atrophy and brain calcifications. All 15 patients had seizures.

In addition, functional studies from zebrafish model also provided parallel evidence that CLDN5 variants cause a neurodevelopmental disorder involving disruption of the blood brain barrier and impaired neuronal function.

This gene has been associated with relevant phenotypes in Gene2Phenotype (CLDN5-related neurodevelopmental disorder with 'limited' rating in the DD panel), but not in OMIM.
Sources: Literature
Intellectual disability v5.166 CLDN5 Achchuthan Shanmugasundram edited their review of gene: CLDN5: Changed phenotypes to: intellectual disability, MONDO:0001071tual
Early onset or syndromic epilepsy v4.44 CLDN5 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: CLDN5.
Acute rhabdomyolysis v1.8 Arina Puzriakova Panel types changed to GMS Rare Disease Virtual; GMS Rare Disease; GMS signed-off
Panel version 1.7 has been signed off on 2023-05-31
Early onset or syndromic epilepsy v4.44 CLDN5 Achchuthan Shanmugasundram Deleted their comment
Early onset or syndromic epilepsy v4.44 CLDN5 Achchuthan Shanmugasundram Classified gene: CLDN5 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.44 CLDN5 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be rated GREEN at the next GMS review.
Early onset or syndromic epilepsy v4.44 CLDN5 Achchuthan Shanmugasundram Gene: cldn5 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.43 CLDN5 Achchuthan Shanmugasundram Classified gene: CLDN5 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.43 CLDN5 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be rated GREEN at the next GMS review.
Early onset or syndromic epilepsy v4.43 CLDN5 Achchuthan Shanmugasundram Gene: cldn5 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.42 CLDN5 Achchuthan Shanmugasundram changed review comment from: PMID: 36477332 identified de novo heterozygous missense variants in CLDN5 in fifteen unrelated patients who presented with a shared constellation of features including developmental delay, seizures (primarily infantile onset focal epilepsy), microcephaly and a recognizable pattern of pontine atrophy and brain calcifications.
Sources: Literature; to: PMID:36477332 reported the identification of de novo heterozygous missense variants in CLDN5 in 15 unrelated patients who presented with a number of clinical features including developmental delay including intellectual disability, seizures (primarily infantile onset focal epilepsy), microcephaly and a recognisable pattern of pontine atrophy and brain calcifications. All 15 patients had seizures.

In addition, functional studies from zebrafish model also provided parallel evidence that CLDN5 variants cause a neurodevelopmental disorder involving disruption of the blood brain barrier and impaired neuronal function.

This gene has been associated with relevant phenotypes in Gene2Phenotype (CLDN5-related neurodevelopmental disorder with 'limited' rating in the DD panel), but not in OMIM.
Sources: Literature
White matter disorders and cerebral calcification - childhood onset v3.11 CLDN5 Achchuthan Shanmugasundram gene: CLDN5 was added
gene: CLDN5 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Literature
Mode of inheritance for gene: CLDN5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CLDN5 were set to 36477332
Phenotypes for gene: CLDN5 were set to epilepsy, MONDO:0005027
Review for gene: CLDN5 was set to GREEN
Added comment: PMID: 36477332 identified de novo heterozygous missense variants in CLDN5 in fifteen unrelated patients who presented with a shared constellation of features including developmental delay, seizures (primarily infantile onset focal epilepsy), microcephaly and a recognizable pattern of pontine atrophy and brain calcifications.
Sources: Literature
Intellectual disability v5.166 CLDN5 Achchuthan Shanmugasundram gene: CLDN5 was added
gene: CLDN5 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: CLDN5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CLDN5 were set to 36477332
Phenotypes for gene: CLDN5 were set to epilepsy, MONDO:0005027
Review for gene: CLDN5 was set to GREEN
Added comment: PMID: 36477332 identified de novo heterozygous missense variants in CLDN5 in fifteen unrelated patients who presented with a shared constellation of features including developmental delay, seizures (primarily infantile onset focal epilepsy), microcephaly and a recognizable pattern of pontine atrophy and brain calcifications.
Sources: Literature
Early onset or syndromic epilepsy v4.42 CLDN5 Achchuthan Shanmugasundram gene: CLDN5 was added
gene: CLDN5 was added to Early onset or syndromic epilepsy. Sources: Literature
Mode of inheritance for gene: CLDN5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CLDN5 were set to 36477332
Phenotypes for gene: CLDN5 were set to epilepsy, MONDO:0005027
Review for gene: CLDN5 was set to GREEN
Added comment: PMID: 36477332 identified de novo heterozygous missense variants in CLDN5 in fifteen unrelated patients who presented with a shared constellation of features including developmental delay, seizures (primarily infantile onset focal epilepsy), microcephaly and a recognizable pattern of pontine atrophy and brain calcifications.
Sources: Literature
Intellectual disability v5.165 KDM2B Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.165 KDM2B Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.165 KDM2B Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.165 TCEAL1 Achchuthan Shanmugasundram Classified gene: TCEAL1 as Amber List (moderate evidence)
Intellectual disability v5.165 TCEAL1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (7 unrelated cases) for this gene to be rated GREEN at the next GMS review.
Intellectual disability v5.165 TCEAL1 Achchuthan Shanmugasundram Gene: tceal1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.165 TCEAL1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.165 TCEAL1 Achchuthan Shanmugasundram Classified gene: TCEAL1 as Amber List (moderate evidence)
Intellectual disability v5.165 TCEAL1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (7 unrelated cases) for this gene to be rated GREEN at the next GMS review.
Intellectual disability v5.165 TCEAL1 Achchuthan Shanmugasundram Gene: tceal1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.164 TCEAL1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.164 TCEAL1 Achchuthan Shanmugasundram Classified gene: TCEAL1 as Amber List (moderate evidence)
Intellectual disability v5.164 TCEAL1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (7 unrelated cases) for this gene to be rated GREEN at the next GMS review.
Intellectual disability v5.164 TCEAL1 Achchuthan Shanmugasundram Gene: tceal1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.164 TCEAL1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.164 TCEAL1 Achchuthan Shanmugasundram Classified gene: TCEAL1 as Amber List (moderate evidence)
Intellectual disability v5.164 TCEAL1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (7 unrelated cases) for this gene to be rated GREEN at the next GMS review.
Intellectual disability v5.164 TCEAL1 Achchuthan Shanmugasundram Gene: tceal1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.164 TCEAL1 Achchuthan Shanmugasundram Classified gene: TCEAL1 as Amber List (moderate evidence)
Intellectual disability v5.164 TCEAL1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (7 unrelated cases) for this gene to be rated GREEN at the next GMS review.
Intellectual disability v5.164 TCEAL1 Achchuthan Shanmugasundram Gene: tceal1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.163 TCEAL1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: TCEAL1.
Intellectual disability v5.163 TCEAL1 Achchuthan Shanmugasundram changed review comment from: PMID:36368327 reported seven unrelated individuals with de novo variants (2 nonsense, 2 frameshift, 2 CNVs & 1 missense variants) in TCEAL1 gene and presenting with an X-linked dominant neurodevelopmental disorder. All these seven individuals had intellectual disability (mild to severe). The other major clinical presentations include hypotonia, abnormal gait, speech impairment, autistic-like behavior, and mildly dysmorphic facial features.

This gene is associated with relevant phenotypes in OMIM (MIM #301094), but not in Gene2Phenotype.
Sources: Literature; to: PMID:36368327 reported seven unrelated individuals with de novo variants (2 nonsense, 2 frameshift, 2 CNVs & 1 missense variants) in TCEAL1 gene and presenting with an X-linked dominant neurodevelopmental disorder. All these seven individuals had intellectual disability (mild to severe). The other major clinical presentations include hypotonia, abnormal gait, speech impairment, autistic-like behaviour, and mildly dysmorphic facial features.

This gene is associated with relevant phenotypes in OMIM (MIM #301094), but not in Gene2Phenotype.
Sources: Literature
Intellectual disability v5.163 TCEAL1 Achchuthan Shanmugasundram gene: TCEAL1 was added
gene: TCEAL1 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: TCEAL1 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: TCEAL1 were set to 36368327
Phenotypes for gene: TCEAL1 were set to Neurodevelopmental disorder with gait disturbance, dysmorphic facies and behavioral abnormalities, X-linked, OMIM:301094
Review for gene: TCEAL1 was set to GREEN
Added comment: PMID:36368327 reported seven unrelated individuals with de novo variants (2 nonsense, 2 frameshift, 2 CNVs & 1 missense variants) in TCEAL1 gene and presenting with an X-linked dominant neurodevelopmental disorder. All these seven individuals had intellectual disability (mild to severe). The other major clinical presentations include hypotonia, abnormal gait, speech impairment, autistic-like behavior, and mildly dysmorphic facial features.

This gene is associated with relevant phenotypes in OMIM (MIM #301094), but not in Gene2Phenotype.
Sources: Literature
Ataxia and cerebellar anomalies - childhood onset v4.13 FEM1C Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: FEM1C.
Ataxia and cerebellar anomalies - childhood onset v4.13 FEM1C Achchuthan Shanmugasundram Classified gene: FEM1C as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - childhood onset v4.13 FEM1C Achchuthan Shanmugasundram Added comment: Comment on list classification: There are two unrelated cases (one in literature and another from Diagnostic Discovery initiative) and functional evidence from animal models in support of the association of this gene to ataxia. Hence, this gene can be rated Green at the next major update.
Ataxia and cerebellar anomalies - childhood onset v4.13 FEM1C Achchuthan Shanmugasundram Gene: fem1c has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - childhood onset v4.12 FEM1C Achchuthan Shanmugasundram commented on gene: FEM1C: PMID:36336956 reported a 9 year-old boy with severe global developmental delay, lack of speech, pyramidal signs and limb ataxia and identified with a heterozygous de novo missense variant c.376G>C (p.Asp126His) in the FEM1C gene. The introduction of the equivalent variant in C. elegans resulted in disabled locomotion caused by synaptic abnormalities and not by muscle dysfunction.

An additional case with a diagnostically reported de novo variant in this gene and a compatible phenotype including intellectual disability and ataxia was identified in the internal Genomics England Clinical Variant Archive (CVA) by the Diagnostic Discovery initiative.

This gene has not yet been associated with relevant phenotypes in OMIM or in Gene2Phenotype.
Ataxia and cerebellar anomalies - childhood onset v4.12 FEM1C Achchuthan Shanmugasundram gene: FEM1C was added
gene: FEM1C was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: FEM1C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FEM1C were set to 36336956
Phenotypes for gene: FEM1C were set to Ataxia, HP:0001251
Review for gene: FEM1C was set to GREEN
Added comment: Sources: Literature
Intellectual disability v5.162 FEM1C Achchuthan Shanmugasundram changed review comment from: Comment on list classification: This gene should be rated AMBER as there are two unrelated cases of intellectual disability reported (one in literature and another from Diagnostic Discovery initiative).; to: Comment on list classification: This gene should be rated AMBER as there are two unrelated cases of intellectual disability (one in literature and another from Diagnostic Discovery initiative).
Intellectual disability v5.162 FEM1C Achchuthan Shanmugasundram Classified gene: FEM1C as Amber List (moderate evidence)
Intellectual disability v5.162 FEM1C Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as there are two unrelated cases of intellectual disability reported (one in literature and another from Diagnostic Discovery initiative).
Intellectual disability v5.162 FEM1C Achchuthan Shanmugasundram Gene: fem1c has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.161 FEM1C Achchuthan Shanmugasundram changed review comment from: This gene should be rated RED as there is only one clear case of intellectual disability reported in literature.

PMID:36336956 reported a 9 year-old boy with severe global developmental delay, lack of speech, pyramidal signs and limb ataxia and identified with a heterozygous de novo missense variant c.376G>C (p.Asp126His) in the FEM1C gene. Cognitive assessment performed at 9 years of age showed that he has moderate intellectual disability.

De novo variant in the same residue (p.Asp126Val) has also been associated with an uncharacterised developmental disorder in PMID:28135719.

An additional case with a diagnostically reported de novo variant in this gene and a compatible phenotype including intellectual disability and ataxia was identified in the internal Genomics England Clinical Variant Archive (CVA) by the Diagnostic Discovery initiative.

This gene has not yet been associated with relevant phenotypes in OMIM or in Gene2Phenotype.
Sources: Literature; to: PMID:36336956 reported a 9 year-old boy with severe global developmental delay, lack of speech, pyramidal signs and limb ataxia and identified with a heterozygous de novo missense variant c.376G>C (p.Asp126His) in the FEM1C gene. Cognitive assessment performed at 9 years of age showed that he has moderate intellectual disability.

De novo variant in the same residue (p.Asp126Val) has also been associated with an uncharacterised developmental disorder in PMID:28135719.

An additional case with a diagnostically reported de novo variant in this gene and a compatible phenotype including intellectual disability and ataxia was identified in the internal Genomics England Clinical Variant Archive (CVA) by the Diagnostic Discovery initiative.

This gene has not yet been associated with relevant phenotypes in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability v5.161 FEM1C Achchuthan Shanmugasundram changed review comment from: This gene should be rated RED as there is only one clear case of intellectual disability reported in literature.

PMID:36336956 reported a 9 year-old boy with severe global developmental delay, lack of speech, pyramidal signs and limb ataxia and identified with a heterozygous de novo missense variant c.376G>C (p.Asp126His) in the FEM1C gene. Cognitive assessment performed at 9 years of age showed that he has moderate intellectual disability.

De novo variant in the same residue (p.Asp126Val) has also been associated with an uncharacterised developmental disorder in PMID:28135719.

This gene has not yet been associated with relevant phenotypes in OMIM or in Gene2Phenotype.
Sources: Literature; to: This gene should be rated RED as there is only one clear case of intellectual disability reported in literature.

PMID:36336956 reported a 9 year-old boy with severe global developmental delay, lack of speech, pyramidal signs and limb ataxia and identified with a heterozygous de novo missense variant c.376G>C (p.Asp126His) in the FEM1C gene. Cognitive assessment performed at 9 years of age showed that he has moderate intellectual disability.

De novo variant in the same residue (p.Asp126Val) has also been associated with an uncharacterised developmental disorder in PMID:28135719.

An additional case with a diagnostically reported de novo variant in this gene and a compatible phenotype including intellectual disability and ataxia was identified in the internal Genomics England Clinical Variant Archive (CVA) by the Diagnostic Discovery initiative.

This gene has not yet been associated with relevant phenotypes in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability v5.161 FEM1C Achchuthan Shanmugasundram edited their review of gene: FEM1C: Changed rating: AMBER
Hereditary spastic paraplegia, adult onset v3.3 PRNP James Polke gene: PRNP was added
gene: PRNP was added to Adult onset hereditary spastic paraplegia. Sources: NHS GMS
Mode of inheritance for gene: PRNP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PRNP were set to 30240140; 8250529; 34746379; 28195350
Phenotypes for gene: PRNP were set to HSP; Gerstmann–Sträussler–Scheinker disease
Penetrance for gene: PRNP were set to Complete
Mode of pathogenicity for gene: PRNP was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: PRNP was set to GREEN
gene: PRNP was marked as current diagnostic
Added comment: HSP can be a rare presenting phenotype for some individuals with inherited prion disease.
Sources: NHS GMS
Severe microcephaly v4.17 ARPC4 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: ARPC4.
Severe microcephaly v4.17 ARPC4 Achchuthan Shanmugasundram Classified gene: ARPC4 as Amber List (moderate evidence)
Severe microcephaly v4.17 ARPC4 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be rated GREEN at the next GMS review.
Severe microcephaly v4.17 ARPC4 Achchuthan Shanmugasundram Gene: arpc4 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v4.16 ARPC4 Achchuthan Shanmugasundram Phenotypes for gene: ARPC4 were changed from Microcephaly; mild motor delays; significant speech impairment to Developmental delay, language impairment, and ocular abnormalities, OMIM:620141; microcephaly, MONDO:0001149
Severe microcephaly v4.15 ARPC4 Achchuthan Shanmugasundram Publications for gene: ARPC4 were set to DOI:https://doi.org/10.1016/j.xhgg.2021.100072
Severe microcephaly v4.14 ARPC4 Achchuthan Shanmugasundram commented on gene: ARPC4: As reviewed by Zornitza Stark, PMID:35047857 reported seven cases from six unrelated families with the same missense variant (p.Arg158Cys) and presenting with developmental and speech delays, of which six individuals from five families presented with microcephaly. Three individuals from two of these families had severe microcephaly with occipitofrontal circumference (OFC) beyond 3 standard deviations below the mean for age. In addition, functional studies showed that the variant is associated with a decreased amount of F-actin in cells from two affected individuals.

This gene has been associated with relevant phenotypes in both OMIM (MIM #620141) and Gene2Phenotype (ARPC4-related microcephaly and developmental delay with 'strong' rating in the DD panel).
Early onset or syndromic epilepsy v4.41 RHEB Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: RHEB.
Early onset or syndromic epilepsy v4.41 RHEB Arina Puzriakova changed review comment from: At least 2 additional cases reported (PMID: 33434304; 37015817) with a spectrum of cortical malformations and brain mosaic RHEB variants. This now meets the diagnostic-grade criteria and therefore this gene should be rated Green.; to: At least 2 additional cases reported (PMID: 33434304; 37015817) with seizures, a spectrum of cortical malformations and brain mosaic RHEB variants. This now meets the diagnostic-grade criteria and therefore this gene should be rated Green.
Early onset or syndromic epilepsy v4.41 RHEB Arina Puzriakova Classified gene: RHEB as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.41 RHEB Arina Puzriakova Gene: rheb has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.40 RHEB Arina Puzriakova changed review comment from: Comment on list classification: There is sufficient evidence to support an association with epilepsy; however, it is worth noting that variants are brain-specific somatic. Still adding to this panel as other somatic mosaic genes (e.g. GNAQ, MTOR, TSC1, TSC2) are included.; to: Comment on list classification: There is sufficient evidence to support an association with epilepsy; however, it is worth noting that variants are brain-specific somatic. Still adding to this panel as other somatic mosaic genes are included (e.g. GNAQ, MTOR, TSC1, TSC2).
Early onset or syndromic epilepsy v4.40 RHEB Arina Puzriakova changed review comment from: Comment on list classification: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; to: Comment on list classification: There is sufficient evidence to support an association with epilepsy; however, it is worth noting that variants are brain-specific somatic. Still adding to this panel as other somatic mosaic genes (e.g. GNAQ, MTOR, TSC1, TSC2) are included.
Early onset or syndromic epilepsy v4.40 RHEB Arina Puzriakova Tag mosaicism tag was added to gene: RHEB.
Early onset or syndromic epilepsy v4.40 RHEB Arina Puzriakova Entity copied from Mosaic brain disorders - deep sequencing v0.116
Early onset or syndromic epilepsy v4.40 RHEB Arina Puzriakova gene: RHEB was added
gene: RHEB was added to Early onset or syndromic epilepsy. Sources: Expert Review Green,Expert list
somatic tags were added to gene: RHEB.
Mode of inheritance for gene: RHEB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RHEB were set to 29051493; 30414531; 33434304; 37015817
Phenotypes for gene: RHEB were set to Epilepsy and cortical dysplasia
Mode of pathogenicity for gene: RHEB was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Severe microcephaly v4.14 ARPC4 Achchuthan Shanmugasundram reviewed gene: ARPC4: Rating: GREEN; Mode of pathogenicity: None; Publications: 35047857; Phenotypes: Developmental delay, language impairment, and ocular abnormalities, OMIM:620141, microcephaly, MONDO:0001149; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Leukodystrophy, adult onset v3.8 NPC1 Achchuthan Shanmugasundram Tag watchlist tag was added to gene: NPC1.
Neurodegenerative disorders, adult onset v4.26 VRK1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: VRK1.
Neurodegenerative disorders, adult onset v4.26 VRK1 Achchuthan Shanmugasundram Classified gene: VRK1 as Amber List (moderate evidence)
Neurodegenerative disorders, adult onset v4.26 VRK1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (five unrelated cases) for this gene to be promoted to GREEN at the next major update.
Neurodegenerative disorders, adult onset v4.26 VRK1 Achchuthan Shanmugasundram Gene: vrk1 has been classified as Amber List (Moderate Evidence).
Neurodegenerative disorders, adult onset v4.25 VRK1 Achchuthan Shanmugasundram Phenotypes for gene: VRK1 were changed from Pontocerebellar hypoplasia 1A (#607596) to Pontocerebellar hypoplasia type 1A, OMIM:607596; spinal muscular atrophy, MONDO:0001516; distal hereditary motor neuropathy, MONDO:0018894; familial amyotrophic lateral sclerosis, MONDO:0005144
Neurodegenerative disorders, adult onset v4.24 VRK1 Achchuthan Shanmugasundram Publications for gene: VRK1 were set to 26583493
Neurodegenerative disorders, adult onset v4.23 VRK1 Achchuthan Shanmugasundram reviewed gene: VRK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26583493, 31837156, 34169149; Phenotypes: Pontocerebellar hypoplasia type 1A, OMIM:607596, spinal muscular atrophy, MONDO:0001516, distal hereditary motor neuropathy, MONDO:0018894, familial amyotrophic lateral sclerosis, MONDO:0005144; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Leukodystrophy, adult onset v3.8 NPC1 Achchuthan Shanmugasundram edited their review of gene: NPC1: Changed rating: AMBER
Leukodystrophy, adult onset v3.8 NPC1 Achchuthan Shanmugasundram Classified gene: NPC1 as Amber List (moderate evidence)
Leukodystrophy, adult onset v3.8 NPC1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are two unrelated cases associating NPC1 with white matter abnormalities in adulthood. However, there are several other cases with childhood-onset and functional evidence from animal models. This gene should be rated AMBER and 'watchlist' tag should be added.
Leukodystrophy, adult onset v3.8 NPC1 Achchuthan Shanmugasundram Gene: npc1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.161 POU3F2 Sarah Leigh Classified gene: POU3F2 as Amber List (moderate evidence)
Intellectual disability v5.161 POU3F2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Intellectual disability v5.161 POU3F2 Sarah Leigh Gene: pou3f2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.161 POU3F2 Sarah Leigh Classified gene: POU3F2 as Amber List (moderate evidence)
Intellectual disability v5.161 POU3F2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Intellectual disability v5.161 POU3F2 Sarah Leigh Gene: pou3f2 has been classified as Amber List (Moderate Evidence).
Leukodystrophy, adult onset v3.7 NPC1 Achchuthan Shanmugasundram Publications for gene: NPC1 were set to 26910362; 29406968
Leukodystrophy, adult onset v3.6 NPC1 Achchuthan Shanmugasundram reviewed gene: NPC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26910362, 27900365, 29406968, 31254056; Phenotypes: Niemann-Pick disease, type C1, OMIM:257220, Niemann-Pick disease, type D, OMIM:257220; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.160 POU3F2 Sarah Leigh gene: POU3F2 was added
gene: POU3F2 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Q2_23_promote_green tags were added to gene: POU3F2.
Mode of inheritance for gene: POU3F2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: POU3F2 were set to 37207645
Phenotypes for gene: POU3F2 were set to neurodevelopmental delay with hyperphagic obesity
Review for gene: POU3F2 was set to GREEN
Added comment: Not associated with a phenotype in OMIM, Gen2Phen or MONDO. PMID: 37207645 reports eight POU3F2 variants in the unrelated cases of neurodevelopmental delay with hyperphagic obesity, with no other variants detected in other candidate genes. Intellectual disability was apparent in 6/7 of these cases from infancy to early childhood. The remaining variant : NM_005604.4 c.135C>A, p.Tyr45* was found in a mother and son, where the son was classified as having intellectual disability, the mother did not. Excluding the mother and son, all of the remaining cases carrying POU3F2 variants had neurodevelopmental delay.
Sources: Literature
Possible mitochondrial disorder, nuclear genes v3.30 IDH3A Sarah Leigh Tag Q2_23_promote_green tag was added to gene: IDH3A.
Possible mitochondrial disorder, nuclear genes v3.30 IDH3A Sarah Leigh Tag Q2_23_promote_green was removed from gene: IDH3A.
Possible mitochondrial disorder, nuclear genes v3.30 IDH3A Sarah Leigh Deleted their comment
Mitochondrial disorders v4.51 IDH3A Sarah Leigh Classified gene: IDH3A as Amber List (moderate evidence)
Mitochondrial disorders v4.51 IDH3A Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Mitochondrial disorders v4.51 IDH3A Sarah Leigh Gene: idh3a has been classified as Amber List (Moderate Evidence).
Possible mitochondrial disorder, nuclear genes v3.30 IDH3A Sarah Leigh Classified gene: IDH3A as Amber List (moderate evidence)
Possible mitochondrial disorder, nuclear genes v3.30 IDH3A Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Possible mitochondrial disorder, nuclear genes v3.30 IDH3A Sarah Leigh Gene: idh3a has been classified as Amber List (Moderate Evidence).
Possible mitochondrial disorder, nuclear genes v3.29 IDH3A Sarah Leigh Tag Q2_23_promote_green tag was added to gene: IDH3A.
Retinal disorders v4.12 IDH3A Sarah Leigh reviewed gene: IDH3A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Possible mitochondrial disorder, nuclear genes v3.29 IDH3A Sarah Leigh reviewed gene: IDH3A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mitochondrial disorders v4.50 IDH3A Sarah Leigh Tag Q2_23_promote_green tag was added to gene: IDH3A.
Mitochondrial disorders v4.50 IDH3A Sarah Leigh edited their review of gene: IDH3A: Added comment: Associated with relevant phenotype in OMIM and as strong Gen2Phen gene. At least nine IDH3A variants have been reported in six unrelated cases of Retinitis pigmentosa 90, OMIM:619007. Mice homozygous for p.E229K variant exhibited signs of retinal stress, those who were compound heterozygous for p.E229K and Idh3a knockout, had more severe retinal degeneration and embryonic lethality was seen in Idh3a knockout mice; reduced mitochondrial function was seen in the equivalent cell lines (PMID: 30478029).; Changed rating: GREEN
Mitochondrial disorders v4.50 IDH3A Sarah Leigh Deleted their comment
Retinal disorders v4.12 IDH3A Sarah Leigh Publications for gene: IDH3A were set to 28412069; 30478029
Possible mitochondrial disorder, nuclear genes v3.29 IDH3A Sarah Leigh Publications for gene: IDH3A were set to 28412069; 28058510
Mitochondrial disorders v4.50 IDH3A Sarah Leigh Publications for gene: IDH3A were set to 28412069; 28058510
Retinal disorders v4.11 IDH3A Sarah Leigh Phenotypes for gene: IDH3A were changed from Retinitis Pigmentosa; Pseudocoloboma to Retinitis pigmentosa 90, OMIM:619007; retinitis pigmentosa 90, MONDO:0033563
Possible mitochondrial disorder, nuclear genes v3.28 IDH3A Sarah Leigh Phenotypes for gene: IDH3A were changed from Infantile encephalopathy; Retinitis pigmentosa with macular pseudocoloboma to Retinitis pigmentosa 90, OMIM:619007; retinitis pigmentosa 90, MONDO:0033563
Mitochondrial disorders v4.49 IDH3A Sarah Leigh Added comment: Comment on phenotypes: Retinitis pigmentosa with macular pseudocoloboma; Infantile encephalopathy
Mitochondrial disorders v4.49 IDH3A Sarah Leigh Phenotypes for gene: IDH3A were changed from Retinitis pigmentosa with macular pseudocoloboma; Infantile encephalopathy to Retinitis pigmentosa 90, OMIM:619007; retinitis pigmentosa 90, MONDO:0033563
Mitochondrial disorders v4.48 IDH3A Sarah Leigh Added comment: Comment on phenotypes: Retinitis pigmentosa 90, OMIM:619007;retinitis pigmentosa 90, MONDO:0033563
Mitochondrial disorders v4.48 IDH3A Sarah Leigh Phenotypes for gene: IDH3A were changed from Retinitis pigmentosa with macular pseudocoloboma; Infantile encephalopathy to Retinitis pigmentosa with macular pseudocoloboma; Infantile encephalopathy
Mitochondrial disorders v4.47 ETFB Sarah Leigh Publications for gene: ETFB were set to 7912128; 12815589
Hyperammonaemia v1.17 ETFB Sarah Leigh Publications for gene: ETFB were set to 27081516
Intellectual disability v5.159 ETFB Sarah Leigh Publications for gene: ETFB were set to 30847515; 11980892; 25778941; 24360804; 27021474; 28489334; 30089828; 36495139
DDG2P v3.6 ETFB Sarah Leigh Publications for gene: ETFB were set to
Fetal anomalies v3.90 ETFB Sarah Leigh Publications for gene: ETFB were set to
Intellectual disability v5.158 ETFB Sarah Leigh Publications for gene: ETFB were set to 0
Acute rhabdomyolysis v1.7 ETFB Sarah Leigh Publications for gene: ETFB were set to 25929793; 32550677
Likely inborn error of metabolism v4.41 ETFB Sarah Leigh Publications for gene: ETFB were set to 27604308
Rhabdomyolysis and metabolic muscle disorders v3.5 ETFB Sarah Leigh Publications for gene: ETFB were set to 25929793
Undiagnosed metabolic disorders v1.591 ETFB Sarah Leigh Publications for gene: ETFB were set to 27604308
Undiagnosed metabolic disorders v1.590 ETFB Sarah Leigh Added comment: Comment on phenotypes: Electron transfer flavoprotein deficiency, beta chain (Disorders of mitochondrial fatty acid oxidation);Glutaric acidemia IIB
Undiagnosed metabolic disorders v1.590 ETFB Sarah Leigh Phenotypes for gene: ETFB were changed from Electron transfer flavoprotein deficiency, beta chain (Disorders of mitochondrial fatty acid oxidation); Glutaric acidemia IIB to Glutaric acidemia IIB, OMIM:231680; multiple acyl-CoA dehydrogenase deficiency, MONDO:0009282
Likely inborn error of metabolism v4.40 ETFB Sarah Leigh Added comment: Comment on phenotypes: Electron transfer flavoprotein deficiency, beta chain (Disorders of mitochondrial fatty acid oxidation)
Likely inborn error of metabolism v4.40 ETFB Sarah Leigh Phenotypes for gene: ETFB were changed from Glutaric acidemia IIB; Electron transfer flavoprotein deficiency, beta chain (Disorders of mitochondrial fatty acid oxidation) to Glutaric acidemia IIB, OMIM:231680; multiple acyl-CoA dehydrogenase deficiency, MONDO:0009282
Leukodystrophy, adult onset v3.6 MAN2B1 Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: MAN2B1.
Leukodystrophy, adult onset v3.6 MAN2B1 Achchuthan Shanmugasundram Classified gene: MAN2B1 as Red List (low evidence)
Leukodystrophy, adult onset v3.6 MAN2B1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is only one family with white matter abnormalities confirmed in adulthood. All other reported cases with white matter abnormalities detected by MRI are during childhood/ adolescence.
Leukodystrophy, adult onset v3.6 MAN2B1 Achchuthan Shanmugasundram Gene: man2b1 has been classified as Red List (Low Evidence).
Rhabdomyolysis and metabolic muscle disorders v3.4 ETFB Sarah Leigh Phenotypes for gene: ETFB were changed from Glutaric acidemia IIB 231680 to Glutaric acidemia IIB, OMIM:231680; multiple acyl-CoA dehydrogenase deficiency, MONDO:0009282
Acute rhabdomyolysis v1.6 ETFB Sarah Leigh Phenotypes for gene: ETFB were changed from Glutaric acidemia IIB, OMIM:231680 to Glutaric acidemia IIB, OMIM:231680; multiple acyl-CoA dehydrogenase deficiency, MONDO:0009282
Intellectual disability v5.157 ETFB Sarah Leigh Phenotypes for gene: ETFB were changed from GLUTARIC ACIDURIA TYPE 2B to Glutaric acidemia IIB, OMIM:231680; multiple acyl-CoA dehydrogenase deficiency, MONDO:0009282
DDG2P v3.5 ETFB Sarah Leigh Phenotypes for gene: ETFB were changed from GLUTARIC ACIDURIA TYPE 2B 231680 to Glutaric acidemia IIB, OMIM:231680; multiple acyl-CoA dehydrogenase deficiency, MONDO:0009282
Leukodystrophy, adult onset v3.5 MAN2B1 Achchuthan Shanmugasundram Deleted their comment
Leukodystrophy, adult onset v3.5 MAN2B1 Achchuthan Shanmugasundram edited their review of gene: MAN2B1: Changed rating: RED
Fetal anomalies v3.89 ETFB Sarah Leigh Phenotypes for gene: ETFB were changed from GLUTARIC ACIDURIA TYPE 2B to Glutaric acidemia IIB, OMIM:231680; multiple acyl-CoA dehydrogenase deficiency, MONDO:0009282
Hyperammonaemia v1.16 ETFB Sarah Leigh Phenotypes for gene: ETFB were changed from Glutaric acidemia IIB 231680 to Glutaric acidemia IIB, OMIM:231680; multiple acyl-CoA dehydrogenase deficiency, MONDO:0009282
Leukodystrophy, adult onset v3.5 MAN2B1 Achchuthan Shanmugasundram changed review comment from: PMID:15534274 reported that MRI from three adult siblings with alpha-mannosidosis (AM) showed cerebellar atrophy and periventricular white matter changes.

PMID:26212233 reported that five of ten patients who have had MRI from the cohort of 34 patients with AM had occipital white matter signal abnormalities.

PMID:33317989 reported cerebral white matter signal abnormalities in 11 (85%) out of 13 untreated AM patients. In addition, cortical atrophy (62%), corpus callosum thinning (23%) and enlargement of perivascular spaces in white matter (38%) was observed.

This gene has been associated with alpha-mannosidosis in both OMIM (MIM #248500) and Gene2Phenotype ('Definitive' rating).; to: PMID:15534274 reported that MRI from three adult siblings with alpha-mannosidosis (AM) showed cerebellar atrophy and periventricular white matter changes.

PMID:26212233 reported that five of ten patients who have had MRI from the cohort of 34 patients with AM had occipital white matter signal abnormalities. However the age of these patients ranged from 7 to 17 years.

PMID:33317989 reported cerebral white matter signal abnormalities in 11 (85%) out of 13 untreated AM patients. In addition, cortical atrophy (62%), corpus callosum thinning (23%) and enlargement of perivascular spaces in white matter (38%) was observed. The age of onset (first symptom) of AM ranged from neonatal period to 4 years. However, four patients were currently adults with MRI taken during their adulthood.

This gene has been associated with alpha-mannosidosis in both OMIM (MIM #248500) and Gene2Phenotype ('Definitive' rating).
Mitochondrial disorders v4.46 ETFB Sarah Leigh Publications for gene: ETFB were set to
Mitochondrial disorders v4.45 ETFB Sarah Leigh Tag Q2_23_promote_green tag was added to gene: ETFB.
Mitochondrial disorders v4.45 ETFB Sarah Leigh edited their review of gene: ETFB: Added comment: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. At least three ETFB variants have been reported in at least three cases.; Changed rating: GREEN; Changed publications to: 7912128, 12815589
Mitochondrial disorders v4.45 ETFB Sarah Leigh Phenotypes for gene: ETFB were changed from Glutaric acidemia IIB ,231680 to Glutaric acidemia IIB, OMIM:231680; multiple acyl-CoA dehydrogenase deficiency, MONDO:0009282
Mitochondrial disorders v4.44 ETFB Sarah Leigh Classified gene: ETFB as Amber List (moderate evidence)
Mitochondrial disorders v4.44 ETFB Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Mitochondrial disorders v4.44 ETFB Sarah Leigh Gene: etfb has been classified as Amber List (Moderate Evidence).
Leukodystrophy, adult onset v3.5 MAN2B1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: MAN2B1.
Leukodystrophy, adult onset v3.5 MAN2B1 Achchuthan Shanmugasundram Classified gene: MAN2B1 as Amber List (moderate evidence)
Leukodystrophy, adult onset v3.5 MAN2B1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to Green at the next major update.
Leukodystrophy, adult onset v3.5 MAN2B1 Achchuthan Shanmugasundram Gene: man2b1 has been classified as Amber List (Moderate Evidence).
Leukodystrophy, adult onset v3.4 MAN2B1 Achchuthan Shanmugasundram Phenotypes for gene: MAN2B1 were changed from Mannosidosis, alpha-, types I and II, MIM# 248500 to Mannosidosis, alpha-, types I and II, OMIM:248500
Leukodystrophy, adult onset v3.3 MAN2B1 Achchuthan Shanmugasundram Publications for gene: MAN2B1 were set to
Leukodystrophy, adult onset v3.2 MAN2B1 Achchuthan Shanmugasundram reviewed gene: MAN2B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15534274, 26212233, 33317989; Phenotypes: Mannosidosis, alpha-, types I and II, OMIM:248500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v4.39 ETFA Sarah Leigh Added comment: Comment on phenotypes: Electron transfer flavoprotein deficiency, alpha chain (Disorders of mitochondrial fatty acid oxidation);Glutaric acidemia IIA
Likely inborn error of metabolism v4.39 ETFA Sarah Leigh Phenotypes for gene: ETFA were changed from Glutaric acidemia IIA, OMIM:231680; multiple acyl-CoA dehydrogenase deficiency, MONDO:0009282 to Glutaric acidemia IIA, OMIM:231680; multiple acyl-CoA dehydrogenase deficiency, MONDO:0009282
Acute rhabdomyolysis v1.5 ETFA Sarah Leigh Phenotypes for gene: ETFA were changed from Glutaric acidemia IIA, OMIM:231680 to Glutaric acidemia IIA, OMIM:231680; multiple acyl-CoA dehydrogenase deficiency, MONDO:0009282
Intellectual disability v5.156 ETFA Sarah Leigh Phenotypes for gene: ETFA were changed from GLUTARIC ACIDURIA TYPE 2A to Glutaric acidemia IIA, OMIM:231680; multiple acyl-CoA dehydrogenase deficiency, MONDO:0009282
DDG2P v3.4 ETFA Sarah Leigh Phenotypes for gene: ETFA were changed from GLUTARIC ACIDURIA TYPE 2A 231680 to Glutaric acidemia IIA, OMIM:231680; multiple acyl-CoA dehydrogenase deficiency, MONDO:0009282
Fetal anomalies v3.88 ETFA Sarah Leigh Phenotypes for gene: ETFA were changed from GLUTARIC ACIDURIA TYPE 2A to Glutaric acidemia IIA, OMIM:231680; multiple acyl-CoA dehydrogenase deficiency, MONDO:0009282
Likely inborn error of metabolism v4.38 ETFA Sarah Leigh Added comment: Comment on phenotypes: Electron transfer flavoprotein deficiency, alpha chain (Disorders of mitochondrial fatty acid oxidation)
Likely inborn error of metabolism v4.38 ETFA Sarah Leigh Phenotypes for gene: ETFA were changed from Electron transfer flavoprotein deficiency, alpha chain (Disorders of mitochondrial fatty acid oxidation); Glutaric acidemia IIA to Glutaric acidemia IIA, OMIM:231680; multiple acyl-CoA dehydrogenase deficiency, MONDO:0009282
Likely inborn error of metabolism v4.37 ETFA Sarah Leigh edited their review of gene: ETFA: Added comment: Associated with phenotype in OMIM and as a definitive Developmental Disorder Gene / G2P. At least five ETFA variants have been reported, two in homozygous and compound heterozygous cases and three as compound heterozygotes (at least eight unrelated cases).; Changed rating: GREEN
Undiagnosed metabolic disorders v1.589 ETFA Sarah Leigh Phenotypes for gene: ETFA were changed from Electron transfer flavoprotein deficiency, alpha chain (Disorders of mitochondrial fatty acid oxidation); Glutaric acidemia IIA to Glutaric acidemia IIA, OMIM:231680; multiple acyl-CoA dehydrogenase deficiency, MONDO:0009282
Rhabdomyolysis and metabolic muscle disorders v3.3 ETFA Sarah Leigh Phenotypes for gene: ETFA were changed from Glutaric acidemia IIA 231680 to Glutaric acidemia IIA, OMIM:231680; multiple acyl-CoA dehydrogenase deficiency, MONDO:0009282
Hyperammonaemia v1.15 ETFA Sarah Leigh Phenotypes for gene: ETFA were changed from Glutaric acidemia IIA 231680 to Glutaric acidemia IIA, OMIM:231680; multiple acyl-CoA dehydrogenase deficiency, MONDO:0009282
Mitochondrial disorders v4.43 ETFA Sarah Leigh Tag Q2_23_promote_green tag was added to gene: ETFA.
Mitochondrial disorders v4.43 ETFA Sarah Leigh changed review comment from: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. At least ETFA five variants have been reported in at least five unrelated cases.; to: Associated with phenotype in OMIM and as a definitive Developmental Disorder Gene / G2P. At least five ETFA variants have been reported, two in homozygous and compound heterozygous cases and three as compound heterozygotes (at least eight unrelated cases).
Mitochondrial disorders v4.43 ETFA Sarah Leigh Classified gene: ETFA as Amber List (moderate evidence)
Mitochondrial disorders v4.43 ETFA Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Mitochondrial disorders v4.43 ETFA Sarah Leigh Gene: etfa has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v4.42 ETFA Sarah Leigh edited their review of gene: ETFA: Added comment: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. At least ETFA five variants have been reported in at least five unrelated cases.; Changed rating: GREEN
Undiagnosed metabolic disorders v1.588 ETFA Sarah Leigh Publications for gene: ETFA were set to 27604308
Likely inborn error of metabolism v4.37 ETFA Sarah Leigh Publications for gene: ETFA were set to 27604308
Mitochondrial disorders v4.42 ETFA Sarah Leigh Publications for gene: ETFA were set to 1882842; 12815589
Mitochondrial disorders v4.41 ETFA Sarah Leigh Phenotypes for gene: ETFA were changed from Glutaric acidemia IIA ,231680 to Glutaric acidemia IIA, OMIM:231680; multiple acyl-CoA dehydrogenase deficiency, MONDO:0009282
Mitochondrial disorders v4.40 ETFA Sarah Leigh Publications for gene: ETFA were set to
Dystonia, chorea or related movement disorder, childhood onset v3.9 COASY Sarah Leigh Publications for gene: COASY were set to 27021474; 24360804
Dystonia, chorea or related movement disorder, adult onset v3.2 COASY Sarah Leigh Publications for gene: COASY were set to 24360804; 27021474
Hereditary ataxia, adult onset v4.12 COASY Sarah Leigh Publications for gene: COASY were set to
DDG2P v3.3 COASY Sarah Leigh Publications for gene: COASY were set to 24360804
Fetal anomalies v3.87 COASY Sarah Leigh Publications for gene: COASY were set to
Likely inborn error of metabolism v4.36 COASY Sarah Leigh Publications for gene: COASY were set to 30089828
Neurodegenerative disorders, adult onset v4.23 COASY Sarah Leigh Publications for gene: COASY were set to 27021474; 28489334; 24360804
Cerebellar hypoplasia v1.73 COASY Sarah Leigh Publications for gene: COASY were set to 30089828; 24360804
Severe microcephaly v4.14 COASY Sarah Leigh Publications for gene: COASY were set to 30089828; 24360804; 27892483
Skeletal dysplasia v4.10 FGF9 Eleanor Williams Phenotypes for gene: FGF9 were changed from ?Multiple synostoses syndrome type 3 612961 to Multiple synostoses syndrome 3, OMIM:612961; multiple synostoses syndrome 3, MONDO:0013064
Skeletal dysplasia v4.9 FGF9 Eleanor Williams Publications for gene: FGF9 were set to 19589401
Skeletal dysplasia v4.8 FGF9 Eleanor Williams Classified gene: FGF9 as Amber List (moderate evidence)
Skeletal dysplasia v4.8 FGF9 Eleanor Williams Added comment: Comment on list classification: Promoting this gene from red to amber but with a recommendation for GREEN rating following GMS review as 4 unrelated cases with variants in FGF9 and a phenotype of multiple synostoses syndrome.
Skeletal dysplasia v4.8 FGF9 Eleanor Williams Gene: fgf9 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v4.7 FGF9 Eleanor Williams Tag watchlist was removed from gene: FGF9.
Tag Q2_23_promote_green tag was added to gene: FGF9.
Skeletal dysplasia v4.7 EN1 Eleanor Williams Classified gene: EN1 as Amber List (moderate evidence)
Skeletal dysplasia v4.7 EN1 Eleanor Williams Added comment: Comment on list classification: Promoting from grey to amber. One patient with a loss of function variant in this gene and a skeletal phenotype reported, plus mouse model with this gene knocked out also shows a skeletal phenotype.

A further 3 patients with 27 and 63Kb deletions 300Kb upstream of this gene also show a skeletal phenotype and this appears to be due to ablation of a long non-coding RNA loci (in mice). However, at this distance it is unlikely to be detected by the Genomics England rare disease pipeline as being associated with EN1, and there are currently no regions on Skeletal dysplasia panel covering that area of chr 2. Therefore, at the present time this gene should be rated amber, following confirmation by the clinical team.
Skeletal dysplasia v4.7 EN1 Eleanor Williams Gene: en1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v4.6 EN1 Eleanor Williams commented on gene: EN1
Unexplained young onset end-stage renal disease v3.3 FAN1 Eleanor Williams Phenotypes for gene: FAN1 were changed from interstitial nephritis; chronic kidney disease; Interstitial nephritis, karyomegalic 614817 to interstitial nephritis; chronic kidney disease; Interstitial nephritis, karyomegalic, OMIM:614817; karyomegalic interstitial nephritis, MONDO:0013898
Unexplained young onset end-stage renal disease v3.2 FAN1 Eleanor Williams Publications for gene: FAN1 were set to 22772369
Unexplained young onset end-stage renal disease v3.1 FAN1 Eleanor Williams commented on gene: FAN1: Mouse model data added by reviewer Yu Leng Phua provides functional data to support this gene-disease association from PMID: 35931300 Airik et al 2022.
Cystic kidney disease v4.6 DZIP1L Eleanor Williams commented on gene: DZIP1L
Cystic kidney disease v4.6 DZIP1L Eleanor Williams Phenotypes for gene: DZIP1L were changed from ARPKD; Polycystic kidney disease 5 617610 to Polycystic kidney disease 5, OMIM:617610; polycystic kidney disease 5, MONDO_0033281
Cystic kidney disease v4.5 DZIP1L Eleanor Williams Publications for gene: DZIP1L were set to 28530676
Intellectual disability v5.155 NUP214 Eleanor Williams Tag Q2_23_promote_green tag was added to gene: NUP214.
Intellectual disability v5.155 NUP214 Eleanor Williams commented on gene: NUP214: After consultation with the Genomics England clinical team it has been decided that there is just enough evidence to promote this gene to green as there are 4 unrelated families and developmental delay is reported in all.
Early onset or syndromic epilepsy v4.39 CPA6 Eleanor Williams commented on gene: CPA6
Early onset or syndromic epilepsy v4.39 CPA6 Eleanor Williams Tag Q2_23_NHS_review tag was added to gene: CPA6.
Tag Q2_23_expert_review tag was added to gene: CPA6.
Early onset or syndromic epilepsy v4.39 CPA6 Eleanor Williams Tag to_be_confirmed_NHSE was removed from gene: CPA6.
Tag Q2_23_demote_red tag was added to gene: CPA6.
Skeletal dysplasia v4.6 GPX4 Achchuthan Shanmugasundram Classified gene: GPX4 as Amber List (moderate evidence)
Skeletal dysplasia v4.6 GPX4 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there is sufficient evidence (>3 unrelated cases) available for this gene to be promoted to GREEN rating at the next major update.
Skeletal dysplasia v4.6 GPX4 Achchuthan Shanmugasundram Gene: gpx4 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v4.5 GPX4 Achchuthan Shanmugasundram Publications for gene: GPX4 were set to 24706940; 32827718; 34931062
Skeletal dysplasia v4.5 GPX4 Achchuthan Shanmugasundram Publications for gene: GPX4 were set to 24706940
Skeletal dysplasia v4.4 GPX4 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: GPX4.
Skeletal dysplasia v4.4 GPX4 Achchuthan Shanmugasundram reviewed gene: GPX4: Rating: GREEN; Mode of pathogenicity: None; Publications: 24706940, 32827718, 34931062; Phenotypes: Spondylometaphyseal dysplasia, Sedaghatian type, OMIM:250220; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v4.4 NMNAT1 Achchuthan Shanmugasundram Publications for gene: NMNAT1 were set to 32533184; 33668384
Skeletal dysplasia v4.4 NMNAT1 Achchuthan Shanmugasundram Publications for gene: NMNAT1 were set to 32533184; 33668384
Skeletal dysplasia v4.4 NMNAT1 Achchuthan Shanmugasundram Publications for gene: NMNAT1 were set to 32533184
Skeletal dysplasia v4.3 NMNAT1 Achchuthan Shanmugasundram Classified gene: NMNAT1 as Amber List (moderate evidence)
Skeletal dysplasia v4.3 NMNAT1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As two of the three reported families were distantly related, this gene should only be rated AMBER with the current evidence. However, 'watchlist' tag was added to review the rating in light of new evidence in the future.
Skeletal dysplasia v4.3 NMNAT1 Achchuthan Shanmugasundram Gene: nmnat1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v4.2 NMNAT1 Achchuthan Shanmugasundram commented on gene: NMNAT1: The 'cnv' tag was added as two of the reported cases harboured duplication variants in homozygous state and the third case harboured duplication variant together with a splicing variant.
Skeletal dysplasia v4.2 NMNAT1 Achchuthan Shanmugasundram Tag watchlist tag was added to gene: NMNAT1.
Tag cnv tag was added to gene: NMNAT1.
Skeletal dysplasia v4.2 NMNAT1 Achchuthan Shanmugasundram reviewed gene: NMNAT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 32533184, 33668384; Phenotypes: Spondyloepiphyseal dysplasia, sensorineural hearing loss, intellectual developmental disorder, and Leber congenital amaurosis, OMIM:619260; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Inherited polyposis and early onset colorectal cancer - germline testing v2.4 GREM1 Kate Downes reviewed gene: GREM1: Rating: GREEN; Mode of pathogenicity: Other; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Skeletal ciliopathies v3.9 INTU Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There are three unrelated cases and supporting functional evidence from mouse model to support the promotion of this gene to GREEN rating at the next GMS review.; to: Comment on list classification: As reviewed by Zornitza Stark, there are three unrelated cases and supporting functional evidence from mouse model to support the promotion of this gene to GREEN rating at the next GMS review.
Skeletal ciliopathies v3.9 INTU Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: INTU.
Skeletal ciliopathies v3.9 INTU Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There are three unrelated cases and supporting functional evidence from mouse model to support the promotion of this gene to GREEN rating at the next GMS update.; to: Comment on list classification: There are three unrelated cases and supporting functional evidence from mouse model to support the promotion of this gene to GREEN rating at the next GMS review.
Skeletal ciliopathies v3.9 INTU Achchuthan Shanmugasundram Classified gene: INTU as Amber List (moderate evidence)
Skeletal ciliopathies v3.9 INTU Achchuthan Shanmugasundram Added comment: Comment on list classification: There are three unrelated cases and supporting functional evidence from mouse model to support the promotion of this gene to GREEN rating at the next GMS update.
Skeletal ciliopathies v3.9 INTU Achchuthan Shanmugasundram Gene: intu has been classified as Amber List (Moderate Evidence).
Skeletal ciliopathies v3.8 INTU Achchuthan Shanmugasundram Phenotypes for gene: INTU were changed from ?Short-rib thoracic dysplasia 20 with polydactyly, OMIM:617925; ?Orofaciodigital syndrome XVII, OMIM:617926 to ?Short-rib thoracic dysplasia 20 with polydactyly, OMIM:617925; ?Orofaciodigital syndrome XVII, OMIM:617926
Skeletal ciliopathies v3.8 INTU Achchuthan Shanmugasundram Phenotypes for gene: INTU were changed from ?Short-rib thoracic dysplasia 20 with polydactyly, OMIM:617925; ?Orofaciodigital syndrome XVII, OMIM:617926 to ?Short-rib thoracic dysplasia 20 with polydactyly, OMIM:617925; ?Orofaciodigital syndrome XVII, OMIM:617926
Skeletal ciliopathies v3.8 INTU Achchuthan Shanmugasundram Phenotypes for gene: INTU were changed from Orofaciodigital syndrome XVII MIM#617926; Short-rib thoracic dysplasia 20 with polydactyly MIM#617925 to ?Short-rib thoracic dysplasia 20 with polydactyly, OMIM:617925; ?Orofaciodigital syndrome XVII, OMIM:617926
Skeletal ciliopathies v3.7 INTU Achchuthan Shanmugasundram Publications for gene: INTU were set to 27158779; 29451301; 20067783
Skeletal ciliopathies v3.6 INTU Achchuthan Shanmugasundram reviewed gene: INTU: Rating: GREEN; Mode of pathogenicity: None; Publications: 20067783, 27158779, 29451301; Phenotypes: ?Short-rib thoracic dysplasia 20 with polydactyly, OMIM:617925, ?Orofaciodigital syndrome XVII, OMIM:617926; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: FILIP1.
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Classified gene: FILIP1 as Amber List (moderate evidence)
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (3 unrelated families) for this gene to be promoted to GREEN rating at the next major update.
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Gene: filip1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram changed review comment from: PMID:36344539 reported a single male with biallelic variant in FILIP1 (c.2665C > T/ p.Arg889Ter) gene and presenting with distal arthrogryposis and mild learning disability.

PMID:37163662 reported five individuals from four unrelated families with four different biallelic variants in FILIP1 gene. The main symptoms in childhood included delayed motor milestones (all four families), delayed speech development (three families), intellectual disability (three families), contractures (2 families), clubfeet (2 families) and microcephaly (2 families). As one of the patients died at the age of 13 months, intellectual disability and speech delay were not evaluated.

This gene has not been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature; to: PMID:36344539 reported a single male with biallelic variant in FILIP1 (c.2665C > T/ p.Arg889Ter) gene and presenting with distal arthrogryposis and mild learning disability.

PMID:37163662 reported five individuals from four unrelated families with four different biallelic variants in FILIP1 gene. The main symptoms in childhood included delayed motor milestones (all four families), delayed speech development (three families), intellectual disability (three families), contractures (2 families), clubfeet (2 families) and microcephaly (2 families). As one of the patients died at the age of 13 months, intellectual disability and speech delay were not evaluated.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Classified gene: FILIP1 as Amber List (moderate evidence)
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (3 unrelated families) for this gene to be promoted to GREEN rating at the next major update.
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Gene: filip1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Classified gene: FILIP1 as Amber List (moderate evidence)
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (3 unrelated families) for this gene to be promoted to GREEN rating at the next major update.
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Gene: filip1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Classified gene: FILIP1 as Amber List (moderate evidence)
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (3 unrelated families) for this gene to be promoted to GREEN rating at the next major update.
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Gene: filip1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.154 FILIP1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.154 FILIP1 Achchuthan Shanmugasundram Classified gene: FILIP1 as Amber List (moderate evidence)
Intellectual disability v5.154 FILIP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (3 unrelated families) for this gene to be promoted to GREEN rating at the next major update.
Intellectual disability v5.154 FILIP1 Achchuthan Shanmugasundram Gene: filip1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.154 FILIP1 Achchuthan Shanmugasundram Classified gene: FILIP1 as Amber List (moderate evidence)
Intellectual disability v5.154 FILIP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (3 unrelated families) for this gene to be promoted to GREEN rating at the next major update.
Intellectual disability v5.154 FILIP1 Achchuthan Shanmugasundram Gene: filip1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.153 FILIP1 Achchuthan Shanmugasundram changed review comment from: Sources: Literature; to: PMID:36344539 reported a single male with biallelic variant in FILIP1 (c.2665C > T/ p.Arg889Ter) gene and presenting with distal arthrogryposis and mild learning disability.

PMID:37163662 reported five individuals from four unrelated families with four different biallelic variants in FILIP1 gene. The main symptoms in childhood included delayed motor milestones (all four families), delayed speech development (three families), intellectual disability (three families), contractures (2 families), clubfeet (2 families) and microcephaly (2 families). As one of the patients died at the age of 13 months, intellectual disability and speech delay were not evaluated.

This gene has not been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Arthrogryposis v5.13 FILIP1 Achchuthan Shanmugasundram Publications for gene: FILIP1 were set to 36943452; 36344539; 37163662
Intellectual disability v5.153 FILIP1 Achchuthan Shanmugasundram gene: FILIP1 was added
gene: FILIP1 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: FILIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FILIP1 were set to 36344539; 37163662
Phenotypes for gene: FILIP1 were set to intellectual disability, MONDO:0001071
Review for gene: FILIP1 was set to GREEN
Added comment: Sources: Literature
Arthrogryposis v5.12 FILIP1 Achchuthan Shanmugasundram Tag Q2_23_NHS_review tag was added to gene: FILIP1.
Arthrogryposis v5.12 FILIP1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: FILIP1.
Arthrogryposis v5.12 FILIP1 Achchuthan Shanmugasundram Classified gene: FILIP1 as Amber List (moderate evidence)
Arthrogryposis v5.12 FILIP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (6 unrelated cases) for this gene to be promoted to GREEN rating in the next major update.
Arthrogryposis v5.12 FILIP1 Achchuthan Shanmugasundram Gene: filip1 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v5.11 FILIP1 Achchuthan Shanmugasundram Publications for gene: FILIP1 were set to PubMed: 36344539; PubMed: 36943452; PMID: 37163662
Arthrogryposis v5.10 FILIP1 Achchuthan Shanmugasundram changed review comment from: PMID:36344539 reported a single male with biallelic variant in FILIP1 (c.2665C > T/ p.Arg889Ter) gene and presenting with distal arthrogryposis with contractures of the knees and elbows, congenital clubfoot, muscular hypotonia, and mild learning disability.

PMID:36943452 reported five individuals from three unrelated families with three different biallelic variants in FILIP1 gene (including the variant reported in the patient from PMID:36344539) and presenting with an overlapping phenotype with congenital contractures affecting shoulder, elbow, hand, hip, knee and foot as well as scoliosis, reduced palmar and plantar skin folds, microcephaly and facial dysmorphism.; to: PMID:36344539 reported a single male with biallelic variant in FILIP1 (c.2665C > T/ p.Arg889Ter) gene and presenting with distal arthrogryposis with contractures of the knees and elbows, congenital clubfoot, muscular hypotonia, and mild learning disability.

PMID:36943452 reported five individuals from three unrelated families with three different biallelic variants in FILIP1 gene (including the variant reported in the patient from PMID:36344539) and presenting with an overlapping phenotype with congenital contractures affecting shoulder, elbow, hand, hip, knee and foot as well as scoliosis, reduced palmar and plantar skin folds, microcephaly and facial dysmorphism.

PMID:37163662 reported five individuals from four unrelated families with four different biallelic variants, out of which three individuals from two different families presented with congenital onset of contractures.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Arthrogryposis v5.10 FILIP1 Achchuthan Shanmugasundram edited their review of gene: FILIP1: Changed publications to: 36943452, 36344539, 37163662
Arthrogryposis v5.10 FILIP1 Achchuthan Shanmugasundram Phenotypes for gene: FILIP1 were changed from neurodevelopmental delay; arthrogryposis; muscular hypotonia; mild learning difficulties to arthrogryposis multiplex congenita, MONDO:0015168
Arthrogryposis v5.9 FILIP1 Achchuthan Shanmugasundram reviewed gene: FILIP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 36943452, 36344539; Phenotypes: arthrogryposis multiplex congenita, MONDO:0015168; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ductal plate malformation v1.22 TULP3 Achchuthan Shanmugasundram Classified gene: TULP3 as Green List (high evidence)
Ductal plate malformation v1.22 TULP3 Achchuthan Shanmugasundram Gene: tulp3 has been classified as Green List (High Evidence).
Ductal plate malformation v1.21 TULP3 Achchuthan Shanmugasundram Publications for gene: TULP3 were set to 36460032; 36276950; 35397207
Ductal plate malformation v1.20 TULP3 Achchuthan Shanmugasundram Phenotypes for gene: TULP3 were changed from cystic kidney disease; ductal plate malformation; congentital hepatic fibrosis; cardiomyopathy to Hepatorenocardiac degenerative fibrosis, OMIM:619902
Ductal plate malformation v1.19 TULP3 Achchuthan Shanmugasundram reviewed gene: TULP3: Rating: GREEN; Mode of pathogenicity: None; Publications: 35397207, 36276950, 36460032; Phenotypes: Hepatorenocardiac degenerative fibrosis, OMIM:619902; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.152 FLNA Tracy Lester reviewed gene: FLNA: Rating: RED; Mode of pathogenicity: None; Publications: 20301392; Phenotypes: Skeletal dysplasia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy v4.4 TULP3 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There are three cases with cardiac hypertrophy and hence this gene can be promoted to GREEN rating at the next major update.; to: Comment on list classification: There are three cases reported with cardiac phenotype and hence this gene can be promoted to GREEN rating at the next major update.
Hypertrophic cardiomyopathy v4.4 TULP3 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: TULP3.
Hypertrophic cardiomyopathy v4.4 TULP3 Achchuthan Shanmugasundram Phenotypes for gene: TULP3 were changed from hypertrophic cardiomyopathy; cystic kidney disease; congenital hepatic fibrosis to Hepatorenocardiac degenerative fibrosis, OMIM:619902
Hypertrophic cardiomyopathy v4.3 TULP3 Achchuthan Shanmugasundram Publications for gene: TULP3 were set to 35397207
Hypertrophic cardiomyopathy v4.2 TULP3 Achchuthan Shanmugasundram Classified gene: TULP3 as Amber List (moderate evidence)
Hypertrophic cardiomyopathy v4.2 TULP3 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are three cases with cardiac hypertrophy and hence this gene can be promoted to GREEN rating at the next major update.
Hypertrophic cardiomyopathy v4.2 TULP3 Achchuthan Shanmugasundram Gene: tulp3 has been classified as Amber List (Moderate Evidence).
Hypertrophic cardiomyopathy v4.1 TULP3 Achchuthan Shanmugasundram changed review comment from: PMID:35397207 reported 15 individuals from eight unrelated families with biallelic variants in TULP3 gene, out of which three individuals from two different families were reported with hypertrophic non-obstructive cardiomyopathy. In addition, experiments in TULP3 knockout zebrafish models showed that no aberrant morphological features were found in the heart tissue, and histological examination found no indication of fibrosis or underlying cellular disruptions.; to: PMID:35397207 reported 15 individuals from eight unrelated families with biallelic variants in TULP3 gene, out of which three individuals from two different families were reported with hypertrophic non-obstructive cardiomyopathy. In addition, experiments in TULP3 knockout zebrafish models showed that no aberrant morphological features were found in the heart tissue, and histological examination found no indication of fibrosis or underlying cellular disruptions.

PMID:36460032 reported an individual with compound heterozygous variants in TULP3 gene and with left ventricular hypertrophy in addition to kidney cysts and liver fibrosis.
Hypertrophic cardiomyopathy v4.1 TULP3 Achchuthan Shanmugasundram edited their review of gene: TULP3: Changed publications to: 35397207, 36460032
Hypertrophic cardiomyopathy v4.1 TULP3 Achchuthan Shanmugasundram changed review comment from: PMID:35397207 reported 15 individuals from eight unrelated families with biallelic variants in TULP3 gene, out of which three individuals from two different families were reported with hypertrophic non-obstructive cardiomyopathy. In addition, experiments in TULP3 knockout zebrafish models recapitulated the phenotypes observed in patients including the kidney cysts.; to: PMID:35397207 reported 15 individuals from eight unrelated families with biallelic variants in TULP3 gene, out of which three individuals from two different families were reported with hypertrophic non-obstructive cardiomyopathy. In addition, experiments in TULP3 knockout zebrafish models showed that no aberrant morphological features were found in the heart tissue, and histological examination found no indication of fibrosis or underlying cellular disruptions.
Cystic kidney disease v4.4 TULP3 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient evidence (8 unrelated cases and supporting functional evidence from animal models) for this gene to be promoted to GREEN rating at the next GMS update.; to: Comment on list classification: As reviewed by John Sayer, there is sufficient evidence (8 unrelated cases and supporting functional evidence from animal models) for this gene to be promoted to GREEN rating at the next GMS update.
Hypertrophic cardiomyopathy v4.1 TULP3 Achchuthan Shanmugasundram reviewed gene: TULP3: Rating: GREEN; Mode of pathogenicity: None; Publications: 35397207; Phenotypes: Hepatorenocardiac degenerative fibrosis, OMIM:619902; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cystic kidney disease v4.4 TULP3 Achchuthan Shanmugasundram changed review comment from: PMID:35397207 reported individuals from eight unrelated families with biallelic variants in TULP3 gene, out of which individuals from six families had kidney abnormalities including presentation of kidney cysts in at least an individual from five families. In addition, experiments in TULP3 knockout zebrafish models recapitulated the phenotypes observed in patients including the kidney cysts.

PMID:36276950 reported two sisters with fibrocystic renal and hepatic disease harboring a homozygous missense mutation in TULP3 (p.Arg382Trp). In addition, experiments with inner medullary collecting duct-3 cells expressing the TULP3 R382W patient variant showed that this variant had a severely reduced ability to localise membrane-associated proteins to the cilium, consistent with a loss of TULP3 function.

PMID:36460032 reported two cases with biallelic variants in TULP3 (patient A: homozygous; patient B: compound heterozygous) and both had cystic kidney disease.

Functional studies from mouse models also showed that knockout mice developed cystic kidney disease (PMIDs: 30799239 & 30799240).; to: PMID:35397207 reported individuals from eight unrelated families with biallelic variants in TULP3 gene, out of which individuals from six families had kidney abnormalities including presentation of kidney cysts in at least an individual from five families. In addition, experiments in TULP3 knockout zebrafish models recapitulated the phenotypes observed in patients including the kidney cysts.

PMID:36276950 reported two sisters with fibrocystic renal and hepatic disease harboring a homozygous missense mutation in TULP3 (p.Arg382Trp). In addition, experiments with inner medullary collecting duct-3 cells expressing the TULP3 R382W patient variant showed that this variant had a severely reduced ability to localise membrane-associated proteins to the cilium, consistent with a loss of TULP3 function.

PMID:36460032 reported two cases with biallelic variants in TULP3 (patient A: homozygous; patient B: compound heterozygous) and both had cystic kidney disease.

Functional studies from mouse models also showed that knockout mice developed cystic kidney disease (PMIDs: 30799239 & 30799240).

This gene has been associated with relevant phenotypes in OMIM (MIM #619902), but not in Gene2Phenotype.
Cystic kidney disease v4.4 TULP3 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: TULP3.
Tag Q2_23_NHS_review tag was added to gene: TULP3.
Cystic kidney disease v4.4 TULP3 Achchuthan Shanmugasundram Deleted their comment
Cystic kidney disease v4.4 TULP3 Achchuthan Shanmugasundram Deleted their comment
Cystic kidney disease v4.4 TULP3 Achchuthan Shanmugasundram Classified gene: TULP3 as Amber List (moderate evidence)
Cystic kidney disease v4.4 TULP3 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (8 unrelated cases and supporting functional evidence from animal models) for this gene to be promoted to GREEN rating at the next GMS update.
Cystic kidney disease v4.4 TULP3 Achchuthan Shanmugasundram Gene: tulp3 has been classified as Amber List (Moderate Evidence).
Cystic kidney disease v4.4 TULP3 Achchuthan Shanmugasundram Classified gene: TULP3 as Amber List (moderate evidence)
Cystic kidney disease v4.4 TULP3 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (8 unrelated cases and supporting functional evidence from animal models) for this gene to be promoted to GREEN rating at the next GMS update.
Cystic kidney disease v4.4 TULP3 Achchuthan Shanmugasundram Gene: tulp3 has been classified as Amber List (Moderate Evidence).
Cystic kidney disease v4.4 TULP3 Achchuthan Shanmugasundram Classified gene: TULP3 as Amber List (moderate evidence)
Cystic kidney disease v4.4 TULP3 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (8 unrelated cases and supporting functional evidence from animal models) for this gene to be promoted to GREEN rating at the next GMS update.
Cystic kidney disease v4.4 TULP3 Achchuthan Shanmugasundram Gene: tulp3 has been classified as Amber List (Moderate Evidence).
Cystic kidney disease v4.3 TULP3 Achchuthan Shanmugasundram Phenotypes for gene: TULP3 were changed from cystic kidney disease; ductal plate malformation; congentital hepatic fibrosis; cardiomyopathy to Hepatorenocardiac degenerative fibrosis, OMIM:619902
Cystic kidney disease v4.2 TULP3 Achchuthan Shanmugasundram Publications for gene: TULP3 were set to 36460032; 36276950; 35397207
Cystic kidney disease v4.1 TULP3 Achchuthan Shanmugasundram reviewed gene: TULP3: Rating: GREEN; Mode of pathogenicity: None; Publications: 30799239, 30799240, 35397207, 36276950, 36460032; Phenotypes: Hepatorenocardiac degenerative fibrosis, OMIM:619902; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.152 TAF4 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient evidence available to promote this gene to GREEN at the next major update.; to: Comment on list classification: There is sufficient evidence available to promote this gene to GREEN rating at the next major update.
Intellectual disability v5.152 TAF4 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.152 TAF4 Achchuthan Shanmugasundram Classified gene: TAF4 as Amber List (moderate evidence)
Intellectual disability v5.152 TAF4 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available to promote this gene to GREEN at the next major update.
Intellectual disability v5.152 TAF4 Achchuthan Shanmugasundram Gene: taf4 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.152 TAF4 Achchuthan Shanmugasundram Classified gene: TAF4 as Amber List (moderate evidence)
Intellectual disability v5.152 TAF4 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available to promote this gene to GREEN at the next major update.
Intellectual disability v5.152 TAF4 Achchuthan Shanmugasundram Gene: taf4 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - childhood onset v4.11 INTS11 Arina Puzriakova Entity copied from Intellectual disability - microarray and sequencing v5.151
Ataxia and cerebellar anomalies - childhood onset v4.11 INTS11 Arina Puzriakova gene: INTS11 was added
gene: INTS11 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Amber,Literature
Q2_23_promote_green tags were added to gene: INTS11.
Mode of inheritance for gene: INTS11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INTS11 were set to 37054711
Phenotypes for gene: INTS11 were set to Complex neurodevelopmental disorder, MONDO:0100038
Severe microcephaly v4.13 INTS11 Arina Puzriakova Entity copied from Intellectual disability - microarray and sequencing v5.151
Severe microcephaly v4.13 INTS11 Arina Puzriakova gene: INTS11 was added
gene: INTS11 was added to Severe microcephaly. Sources: Expert Review Amber,Literature
Q2_23_promote_green tags were added to gene: INTS11.
Mode of inheritance for gene: INTS11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INTS11 were set to 37054711
Phenotypes for gene: INTS11 were set to Complex neurodevelopmental disorder, MONDO:0100038
Intellectual disability v5.151 INTS11 Arina Puzriakova Phenotypes for gene: INTS11 were changed from intellectual disability, MONDO:0001071 to Complex neurodevelopmental disorder, MONDO:0100038
Intellectual disability v5.150 INTS11 Arina Puzriakova commented on gene: INTS11
Intellectual disability v5.150 TAF4 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: TAF4.
Fetal anomalies v3.86 PRKACB Arina Puzriakova Entity copied from Skeletal ciliopathies v3.6
Fetal anomalies v3.86 PRKACB Arina Puzriakova gene: PRKACB was added
gene: PRKACB was added to Fetal anomalies. Sources: Expert Review Amber,Literature
Q2_23_promote_green tags were added to gene: PRKACB.
Mode of inheritance for gene: PRKACB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PRKACB were set to 33058759
Phenotypes for gene: PRKACB were set to Cardioacrofacial dysplasia 2, OMIM:619143
Penetrance for gene: PRKACB were set to unknown
Mode of pathogenicity for gene: PRKACB was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Fetal anomalies v3.85 PRKACA Arina Puzriakova Entity copied from Skeletal ciliopathies v3.6
Fetal anomalies v3.85 PRKACA Arina Puzriakova gene: PRKACA was added
gene: PRKACA was added to Fetal anomalies. Sources: Expert Review Amber,Literature
Q2_23_promote_green tags were added to gene: PRKACA.
Mode of inheritance for gene: PRKACA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PRKACA were set to 33058759; 31130284
Phenotypes for gene: PRKACA were set to Cardioacrofacial dysplasia 1, OMIM:619142
Limb disorders v4.5 PRKACA Arina Puzriakova Entity copied from Skeletal ciliopathies v3.6
Limb disorders v4.5 PRKACA Arina Puzriakova gene: PRKACA was added
gene: PRKACA was added to Limb disorders. Sources: Expert Review Amber,Literature
Q2_23_promote_green tags were added to gene: PRKACA.
Mode of inheritance for gene: PRKACA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PRKACA were set to 33058759; 31130284
Phenotypes for gene: PRKACA were set to Cardioacrofacial dysplasia 1, OMIM:619142
Skeletal ciliopathies v3.6 PRKACA Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: PRKACA.
Skeletal ciliopathies v3.6 PRKACA Arina Puzriakova changed review comment from: Comment on list classification: New gene added by Zornitza Stark. There is sufficient evidence to promote this gene to Green at the next GMS panel update. At least 3 unrelated cases reported in literature (PMID: 33058759) and an additional case under the care of an NHS colleague with the same missense variant (p.Gly137Arg) and a limb phenotype.; to: Comment on list classification: New gene added by Zornitza Stark. There is sufficient evidence to promote this gene to Green at the next GMS panel update. At least 3 unrelated cases reported in literature (PMID: 33058759) and an additional case under the care of an NHS colleague with the same de novo missense variant (p.Gly137Arg) and a limb phenotype (reported features include micromelia, polydactyly and AVSD).
Skeletal ciliopathies v3.6 PRKACA Arina Puzriakova Classified gene: PRKACA as Amber List (moderate evidence)
Skeletal ciliopathies v3.6 PRKACA Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark. There is sufficient evidence to promote this gene to Green at the next GMS panel update. At least 3 unrelated cases reported in literature (PMID: 33058759) and an additional case under the care of an NHS colleague with the same missense variant (p.Gly137Arg) and a limb phenotype.
Skeletal ciliopathies v3.6 PRKACA Arina Puzriakova Gene: prkaca has been classified as Amber List (Moderate Evidence).
Skeletal ciliopathies v3.5 PRKACB Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: PRKACB.
Skeletal ciliopathies v3.5 PRKACB Arina Puzriakova changed review comment from: Comment on list classification: New gene added by Konstantinos Varvagiannis. Rating Amber based on the evidence provided in one publication (PMID:33058759) reporting 2/4 unrelated individuals with ID among other features, although this presentation was mild in one of these cases.; to: Comment on list classification: New gene added by Konstantinos Varvagiannis. There is sufficient evidence to promote this gene to Green at the next GMS panel update. At least 4 unrelated cases, displaying a ciliopathy-like phenotype.
Skeletal ciliopathies v3.5 PRKACB Arina Puzriakova Entity copied from Intellectual disability - microarray and sequencing v5.150
Skeletal ciliopathies v3.5 PRKACB Arina Puzriakova gene: PRKACB was added
gene: PRKACB was added to Skeletal ciliopathies. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: PRKACB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PRKACB were set to 33058759
Phenotypes for gene: PRKACB were set to Cardioacrofacial dysplasia 2, OMIM:619143
Penetrance for gene: PRKACB were set to unknown
Mode of pathogenicity for gene: PRKACB was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability v5.150 PRKACB Arina Puzriakova Phenotypes for gene: PRKACB were changed from Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability to Cardioacrofacial dysplasia 2, OMIM:619143
Limb disorders v4.4 PRKACB Arina Puzriakova Phenotypes for gene: PRKACB were changed from Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability to Cardioacrofacial dysplasia 2, OMIM:619143
Skeletal ciliopathies v3.4 PRKACA Arina Puzriakova Phenotypes for gene: PRKACA were changed from Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth to Cardioacrofacial dysplasia 1, OMIM:619142
Intellectual disability v5.149 TAF4 Achchuthan Shanmugasundram Phenotypes for gene: TAF4 were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.149 TAF4 Achchuthan Shanmugasundram Phenotypes for gene: TAF4 were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.148 TAF4 Achchuthan Shanmugasundram Phenotypes for gene: TAF4 were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.149 TAF4 Achchuthan Shanmugasundram Phenotypes for gene: TAF4 were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.147 TAF4 Achchuthan Shanmugasundram Publications for gene: TAF4 were set to 27026076; 28191890; 33875846; 35904126
Intellectual disability v5.148 TAF4 Achchuthan Shanmugasundram Phenotypes for gene: TAF4 were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.148 TAF4 Achchuthan Shanmugasundram Phenotypes for gene: TAF4 were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.148 TAF4 Achchuthan Shanmugasundram Phenotypes for gene: TAF4 were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.147 TAF4 Achchuthan Shanmugasundram Publications for gene: TAF4 were set to 27026076; 28191890; 33875846; 35904126
Intellectual disability v5.148 TAF4 Achchuthan Shanmugasundram Phenotypes for gene: TAF4 were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.148 TAF4 Achchuthan Shanmugasundram Phenotypes for gene: TAF4 were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.148 TAF4 Achchuthan Shanmugasundram Phenotypes for gene: TAF4 were changed from Developmental disorder to intellectual disability, MONDO:0001071
Intellectual disability v5.147 TAF4 Achchuthan Shanmugasundram Publications for gene: TAF4 were set to 27026076; 28191890; 33875846; 35904126
Intellectual disability v5.147 TAF4 Achchuthan Shanmugasundram Publications for gene: TAF4 were set to 27026076; 28191890; 33875846; 35904126
Intellectual disability v5.147 TAF4 Achchuthan Shanmugasundram Publications for gene: TAF4 were set to 27026076; 28191890; 33875846; 35904126
Intellectual disability v5.147 TAF4 Achchuthan Shanmugasundram Publications for gene: TAF4 were set to 27026076; 28191890; 33875846; 35904126
Intellectual disability v5.147 TAF4 Achchuthan Shanmugasundram Publications for gene: TAF4 were set to 27026076; 28191890; 33875846; 35904126
Intellectual disability v5.147 TAF4 Achchuthan Shanmugasundram Publications for gene: TAF4 were set to 33875846; 28191890; 27026076
Intellectual disability v5.146 TAF4 Achchuthan Shanmugasundram Mode of inheritance for gene: TAF4 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.146 TAF4 Achchuthan Shanmugasundram Mode of inheritance for gene: TAF4 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.146 TAF4 Achchuthan Shanmugasundram Mode of inheritance for gene: TAF4 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.146 TAF4 Achchuthan Shanmugasundram Mode of inheritance for gene: TAF4 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.146 TAF4 Achchuthan Shanmugasundram Mode of inheritance for gene: TAF4 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.146 TAF4 Achchuthan Shanmugasundram Mode of inheritance for gene: TAF4 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.145 TAF4 Achchuthan Shanmugasundram reviewed gene: TAF4: Rating: GREEN; Mode of pathogenicity: None; Publications: 28191890, 33875846, 35904126; Phenotypes: intellectual disability, MONDO:0001071; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Classified gene: ZMYND8 as Amber List (moderate evidence)
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (>3 unrelated cases) for this gene to be rated GREEN at the next major update.
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Gene: zmynd8 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Classified gene: ZMYND8 as Amber List (moderate evidence)
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (>3 unrelated cases) for this gene to be rated GREEN at the next major update.
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Gene: zmynd8 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Classified gene: ZMYND8 as Amber List (moderate evidence)
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (>3 unrelated cases) for this gene to be rated GREEN at the next major update.
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Gene: zmynd8 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Classified gene: ZMYND8 as Amber List (moderate evidence)
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (>3 unrelated cases) for this gene to be rated GREEN at the next major update.
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Gene: zmynd8 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Classified gene: ZMYND8 as Amber List (moderate evidence)
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (>3 unrelated cases) for this gene to be rated GREEN at the next major update.
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Gene: zmynd8 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: ZMYND8.
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Classified gene: ZMYND8 as Amber List (moderate evidence)
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (>3 unrelated cases) for this gene to be rated GREEN at the next major update.
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Gene: zmynd8 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.144 ZMYND8 Achchuthan Shanmugasundram Mode of inheritance for gene: ZMYND8 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.144 ZMYND8 Achchuthan Shanmugasundram Mode of inheritance for gene: ZMYND8 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.144 ZMYND8 Achchuthan Shanmugasundram Mode of inheritance for gene: ZMYND8 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.144 ZMYND8 Achchuthan Shanmugasundram Mode of inheritance for gene: ZMYND8 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.144 ZMYND8 Achchuthan Shanmugasundram Mode of inheritance for gene: ZMYND8 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.144 ZMYND8 Achchuthan Shanmugasundram Mode of inheritance for gene: ZMYND8 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.144 ZMYND8 Achchuthan Shanmugasundram Mode of inheritance for gene: ZMYND8 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.143 ZMYND8 Achchuthan Shanmugasundram edited their review of gene: ZMYND8: Added comment: As reviewed by Konstantinos Varvagiannis, PMID:35916866 reported intellectual disability in10 out of 11 unrelated cases, of which one patient had profound ID and two had moderate ID.

This gene has not yet been associated with phenotypes in OMIM, but has been reported in Gene2Phenotype (with 'moderate' rating in the DD panel).; Changed phenotypes to: intellectual disability, MONDO:0001071
Intellectual disability v5.143 ZMYND8 Achchuthan Shanmugasundram reviewed gene: ZMYND8: Rating: GREEN; Mode of pathogenicity: None; Publications: 32530565, 35916866; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.143 ZMYND15 Achchuthan Shanmugasundram Publications for gene: ZMYND15 were set to 35916866; 32530565
Intellectual disability v5.142 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14, OMIM:615842 to ?Spermatogenic failure 14, OMIM:615842
Intellectual disability v5.141 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14, OMIM:615842 to ?Spermatogenic failure 14, OMIM:615842
Intellectual disability v5.143 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14, OMIM:615842 to ?Spermatogenic failure 14, OMIM:615842
Intellectual disability v5.142 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14, OMIM:615842 to ?Spermatogenic failure 14, OMIM:615842
Intellectual disability v5.141 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14, OMIM:615842 to ?Spermatogenic failure 14, OMIM:615842
Intellectual disability v5.141 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14, OMIM:615842 to ?Spermatogenic failure 14, OMIM:615842
Intellectual disability v5.142 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14, OMIM:615842 to ?Spermatogenic failure 14, OMIM:615842
Intellectual disability v5.142 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14, OMIM:615842 to ?Spermatogenic failure 14, OMIM:615842
Intellectual disability v5.141 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14, OMIM:615842 to ?Spermatogenic failure 14, OMIM:615842
Intellectual disability v5.142 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14, OMIM:615842 to ?Spermatogenic failure 14, OMIM:615842
Intellectual disability v5.141 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14 OMIM:615842 to ?Spermatogenic failure 14, OMIM:615842
Intellectual disability v5.140 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14, OMIM:615842 to ?Spermatogenic failure 14 OMIM:615842
Intellectual disability v5.141 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14, OMIM:615842 to ?Spermatogenic failure 14, OMIM:615842
Intellectual disability v5.141 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14, OMIM:615842 to ?Spermatogenic failure 14, OMIM:615842
Intellectual disability v5.141 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14 OMIM:615842 to ?Spermatogenic failure 14, OMIM:615842
Intellectual disability v5.140 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14 OMIM:615842 to ?Spermatogenic failure 14 OMIM:615842
Intellectual disability v5.140 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14 OMIM:615842 to ?Spermatogenic failure 14 OMIM:615842
Intellectual disability v5.140 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14 OMIM:615842 to ?Spermatogenic failure 14 OMIM:615842
Intellectual disability v5.140 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14 OMIM:615842 to ?Spermatogenic failure 14 OMIM:615842
Intellectual disability v5.140 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from Delayed speech and language development; Motor delay; Intellectual disability; Abnormality of cardiovascular system morphology; Hearing abnormality; Abnormality of vision; Abnormality of the face; Seizures to ?Spermatogenic failure 14 OMIM:615842
Intellectual disability v5.139 ZMYND15 Achchuthan Shanmugasundram commented on gene: ZMYND15
Intellectual disability v5.139 ZMYND15 Achchuthan Shanmugasundram Classified gene: ZMYND15 as No list
Intellectual disability v5.139 ZMYND15 Achchuthan Shanmugasundram Gene: zmynd15 has been removed from the panel.
Intellectual disability v5.139 ZMYND15 Achchuthan Shanmugasundram Classified gene: ZMYND15 as No list
Intellectual disability v5.139 ZMYND15 Achchuthan Shanmugasundram Gene: zmynd15 has been removed from the panel.
Intellectual disability v5.139 ZMYND15 Achchuthan Shanmugasundram Classified gene: ZMYND15 as No list
Intellectual disability v5.139 ZMYND15 Achchuthan Shanmugasundram Gene: zmynd15 has been removed from the panel.
Intellectual disability v5.139 ZMYND15 Achchuthan Shanmugasundram Classified gene: ZMYND15 as No list
Intellectual disability v5.139 ZMYND15 Achchuthan Shanmugasundram Gene: zmynd15 has been removed from the panel.
Intellectual disability v5.139 ZMYND15 Achchuthan Shanmugasundram Classified gene: ZMYND15 as No list
Intellectual disability v5.139 ZMYND15 Achchuthan Shanmugasundram Gene: zmynd15 has been removed from the panel.
Intellectual disability v5.138 ZMYND15 Achchuthan Shanmugasundram Classified gene: ZMYND15 as No list
Intellectual disability v5.138 ZMYND15 Achchuthan Shanmugasundram Gene: zmynd15 has been removed from the panel.
Intellectual disability v5.138 ZMYND15 Achchuthan Shanmugasundram Classified gene: ZMYND15 as No list
Intellectual disability v5.138 ZMYND15 Achchuthan Shanmugasundram Gene: zmynd15 has been removed from the panel.
Intellectual disability v5.138 ZMYND15 Achchuthan Shanmugasundram Classified gene: ZMYND15 as No list
Intellectual disability v5.138 ZMYND15 Achchuthan Shanmugasundram Gene: zmynd15 has been removed from the panel.
Intellectual disability v5.137 ZMYND15 Achchuthan Shanmugasundram Tag curated_removed tag was added to gene: ZMYND15.
Hereditary neuropathy or pain disorder v3.31 NTRK1 Achchuthan Shanmugasundram changed review comment from: I agree with Zornitza Stark that it is a complex phenotype. However, neuropathy has been associated with the phenotype in sufficient number of cases and been reviewed by several expert reviewers. Hence, the rating should remain as Green.

This gene has been associated with relevant phenotypes in both OMIM (MIM #256800) and Gene2Phenotype (with 'definitive' rating in DD and skin panels.; to: I agree with Zornitza Stark that it is a complex phenotype. However, neuropathy has been associated with the phenotype in sufficient number of cases and been reviewed by several expert reviewers. Hence, the rating should remain as Green.

This gene has been associated with relevant phenotypes in both OMIM (MIM #256800) and Gene2Phenotype (with 'definitive' rating in DD and skin panels).
COVID-19 research v1.136 ABCC1 Jamal Nasir reviewed gene: ABCC1: Rating: RED; Mode of pathogenicity: Other; Publications: ; Phenotypes: COVID-19; Mode of inheritance: Unknown
Arthrogryposis v5.9 FILIP1 Simon Thomas gene: FILIP1 was added
gene: FILIP1 was added to Arthrogryposis. Sources: Literature
Mode of inheritance for gene: FILIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FILIP1 were set to PubMed: 36344539; PubMed: 36943452; PMID: 37163662
Phenotypes for gene: FILIP1 were set to neurodevelopmental delay; arthrogryposis; muscular hypotonia; mild learning difficulties
Penetrance for gene: FILIP1 were set to unknown
Review for gene: FILIP1 was set to GREEN
Added comment: FILIP1 is not an OMIM Morbid gene. All variants submitted to ClinVar are missense variants of uncertain clinical significance and there are only 3 variants recorded in HDMDPro as?DM.

However, two publications in 2023 have established a gene-disease association in 7 unrelated families. All were consanguineous and had a homozygous FILIP1 variant (5 x LoF and 2 x missense). There is also a mouse model (PMID: 29618024).
Sources: Literature
Hereditary neuropathy or pain disorder v3.31 NTRK1 Achchuthan Shanmugasundram Phenotypes for gene: NTRK1 were changed from Hereditary Neuropathies; Insensitivity to pain, congenital, with anhidrosis to Hereditary Neuropathies; Insensitivity to pain, congenital, with anhidrosis, OMIM:256800
Hereditary neuropathy or pain disorder v3.30 NTRK1 Achchuthan Shanmugasundram reviewed gene: NTRK1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Insensitivity to pain, congenital, with anhidrosis, OMIM:256800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v3.30 MYH14 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: MYH14.
Hereditary neuropathy or pain disorder v3.30 MYH14 Achchuthan Shanmugasundram Classified gene: MYH14 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v3.30 MYH14 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are four families reported with the same variant (p.Arg941Leu) and with supporting functional studies characterising this variant. As the reported cases came from both Korean and North American families, it is not likely to be a founder variant. Hence, this gene can be promoted to GREEN rating at the next GMS update.
Hereditary neuropathy or pain disorder v3.30 MYH14 Achchuthan Shanmugasundram Gene: myh14 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v3.29 MYH14 Achchuthan Shanmugasundram Phenotypes for gene: MYH14 were changed from ?Peripheral neuropathy, myopathy, hoarseness, and hearing loss, 614369 to ?Peripheral neuropathy, myopathy, hoarseness, and hearing loss, OMIM:614369
Hereditary neuropathy or pain disorder v3.28 MYH14 Achchuthan Shanmugasundram Publications for gene: MYH14 were set to 30373780; 21480433; 27875632
Hereditary neuropathy or pain disorder v3.27 MYH14 Achchuthan Shanmugasundram reviewed gene: MYH14: Rating: GREEN; Mode of pathogenicity: None; Publications: 21480433, 27875632, 31231018, 35274842; Phenotypes: ?Peripheral neuropathy, myopathy, hoarseness, and hearing loss, OMIM:614369; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia, adult onset v4.11 RFC1 Sarah Leigh commented on gene: RFC1: Five recent papers (PMID: 35883251; 36250766; 36289003; 36524104; 36478048) report nine RFC1 pathogenic variants in trans with the RFC1_AAGGG expansion variant in at least nine unrelated cases. To date such variants have not been detected in the absence of the RFC1_AAGGG, which is why this gene is rated as Red in PanelApp. Detection of the RFC1_AAGGG expansion variant must be validated within the Genomics England pipeline and will be added to PanelApp in due course.
Hereditary ataxia, adult onset v4.11 RFC1 Sarah Leigh reviewed gene: RFC1: Rating: RED; Mode of pathogenicity: None; Publications: 35883251, 36250766, 36289003, 36524104, 36478048; Phenotypes: ; Mode of inheritance: None
Hereditary neuropathy or pain disorder v3.27 RFC1 Sarah Leigh Phenotypes for gene: RFC1 were changed from Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome, OMIM:614575; cerebellar ataxia, neuropathy, and vestibular areflexia syndrome, MONDO:0013809; chronic idiopathic axonal polyneuropathy; chronic polyneuropathy, MONDO:0003335 to Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome, OMIM:614575; cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome, MONDO:0044720
Hereditary ataxia, adult onset v4.11 RFC1 Sarah Leigh Phenotypes for gene: RFC1 were changed from Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome, OMIM:614575; cerebellar ataxia, neuropathy, and vestibular areflexia syndrome, MONDO:0013809; chronic idiopathic axonal polyneuropathy; chronic polyneuropathy, MONDO:0003335 to Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome, OMIM:614575; cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome, MONDO:0044720
Breast cancer pertinent cancer susceptibility v2.1 CDH1 Lauma Freimane gene: CDH1 was added
gene: CDH1 was added to Breast cancer pertinent cancer susceptibility. Sources: Literature
Mode of inheritance for gene: CDH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDH1 were set to 36436516
Phenotypes for gene: CDH1 were set to Lobular breast cancer
Review for gene: CDH1 was set to GREEN
Added comment: Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v4.22 TLR7 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: TLR7.
Likely inborn error of metabolism v4.35 LETM1 Sarah Leigh Classified gene: LETM1 as Amber List (moderate evidence)
Likely inborn error of metabolism v4.35 LETM1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Likely inborn error of metabolism v4.35 LETM1 Sarah Leigh Gene: letm1 has been classified as Amber List (Moderate Evidence).
Breast cancer pertinent cancer susceptibility v2.1 ATRIP Lauma Freimane gene: ATRIP was added
gene: ATRIP was added to Breast cancer pertinent cancer susceptibility. Sources: Literature
Mode of inheritance for gene: ATRIP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATRIP were set to 36977412
Phenotypes for gene: ATRIP were set to Hereditary breast cancer
Review for gene: ATRIP was set to GREEN
gene: ATRIP was marked as current diagnostic
Added comment: Meta-analysis confirms ATRIP role in breast cancer development (https://doi.org/10.1101/2022.06.17.22276537).
Variants in ATRIP are associated with breast cancer susceptibility in the Polish population and UK Biobank.
Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v4.22 TLR7 Achchuthan Shanmugasundram Added comment: Comment on mode of pathogenicity: As reviewed by Boaz Palterer, gain-of-function variants are associated with systemic lupus erythematosus.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.22 TLR7 Achchuthan Shanmugasundram Mode of pathogenicity for gene: TLR7 was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Primary immunodeficiency or monogenic inflammatory bowel disease v4.21 TLR7 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Boaz Palterer, there are three unrelated cases and functional evidence from mouse models in support of the association of X-linked dominant variants from TLR7 gene to Systemic lupus erythematosus. Hence, this gene can be promoted to GREEN rating at the next major update.; to: Comment on list classification: As reviewed by Boaz Palterer, there are three unrelated cases and functional evidence from mouse models in support of the association of X-linked dominant variants from TLR7 gene to systemic lupus erythematosus. Hence, this gene can be promoted to GREEN rating at the next major update.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.21 TLR7 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There are three cases and supporting functional evidence available for systemic lupus erythematosus caused by X-linked dominant variants. However, there are only two unrelated cases in support of COVID19-related immunodeficiency caused by X-linked recessive variants. Hence, the MOI should be updated from "X-LINKED: hemizygous mutation in males, biallelic mutations in females" to "X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)".
Primary immunodeficiency or monogenic inflammatory bowel disease v4.21 TLR7 Achchuthan Shanmugasundram Mode of inheritance for gene: TLR7 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mitochondrial disorders v4.39 LETM1 Sarah Leigh Classified gene: LETM1 as Amber List (moderate evidence)
Mitochondrial disorders v4.39 LETM1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Mitochondrial disorders v4.39 LETM1 Sarah Leigh Gene: letm1 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.20 TLR7 Achchuthan Shanmugasundram Classified gene: TLR7 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.20 TLR7 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Boaz Palterer, there are three unrelated cases and functional evidence from mouse models in support of the association of X-linked dominant variants from TLR7 gene to Systemic lupus erythematosus. Hence, this gene can be promoted to GREEN rating at the next major update.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.20 TLR7 Achchuthan Shanmugasundram Gene: tlr7 has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v4.38 LETM1 Sarah Leigh reviewed gene: LETM1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Likely inborn error of metabolism v4.34 LETM1 Sarah Leigh reviewed gene: LETM1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Primary immunodeficiency or monogenic inflammatory bowel disease v4.19 TLR7 Achchuthan Shanmugasundram Phenotypes for gene: TLR7 were changed from Immunodeficiency 74, COVID19-related, X-linked, MIM# 301051 to Systemic lupus erythematosus 17, OMIM:301080; Immunodeficiency 74, COVID19-related, X-linked, OMIM:301051
Primary immunodeficiency or monogenic inflammatory bowel disease v4.18 TLR7 Achchuthan Shanmugasundram Publications for gene: TLR7 were set to 32706371
Primary immunodeficiency or monogenic inflammatory bowel disease v4.17 TLR7 Achchuthan Shanmugasundram reviewed gene: TLR7: Rating: GREEN; Mode of pathogenicity: None; Publications: 32706371, 35477763; Phenotypes: Systemic lupus erythematosus 17, OMIM:301080, Immunodeficiency 74, COVID19-related, X-linked, OMIM:301051; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v5.137 PRSS12 Achchuthan Shanmugasundram changed review comment from: Comment on gene classification - This gene should remain as Green rating as there are four unrelated cases and two different variants reported.

PMID:12459588 - Two unrelated families with the same variant (4bp homozygous deletion) and with intellectual disability. Although the cases were thought to be unrelated, they had the same haplotype across the PRSS12 locus, suggesting either distant consanguinity or a founder effect in the Algerian population.

PMID:25529582 - Two unrelated cases with homozygous c.2389C>T/ p.Arg797Cys variants and with severe intellectual disability reported in the Deciphering Developmental Disorders (DDD) study.

In addition, this gene has been associated with intellectual disability in both OMIM (MIM #249500) and Gene2Phenotype (with 'Definitive' rating in the DD panel).; to: Comment on gene classification - This gene should remain as Green as there are four unrelated cases and two different variants reported.

PMID:12459588 - Two unrelated families with the same variant (4bp homozygous deletion) and with intellectual disability. Although the cases were thought to be unrelated, they had the same haplotype across the PRSS12 locus, suggesting either distant consanguinity or a founder effect in the Algerian population.

PMID:25529582 - Two unrelated cases with homozygous c.2389C>T/ p.Arg797Cys variants and with severe intellectual disability reported in the Deciphering Developmental Disorders (DDD) study.

In addition, this gene has been associated with intellectual disability in both OMIM (MIM #249500) and Gene2Phenotype (with 'Definitive' rating in the DD panel).
Intellectual disability v5.137 PRSS12 Achchuthan Shanmugasundram changed review comment from: PMID:12459588 - Two unrelated families with the same variant (4bp homozygous deletion) and with intellectual disability. Although the cases were thought to be unrelated, they had the same haplotype across the PRSS12 locus, suggesting either distant consanguinity or a founder effect in the Algerian population.

PMID:25529582 - Two unrelated cases with homozygous c.2389C>T/ p.Arg797Cys variants and with severe intellectual disability reported in the Deciphering Developmental Disorders (DDD) study.

In addition, this gene has been associated with intellectual disability in both OMIM (MIM #249500) and Gene2Phenotype (with 'Definitive' rating in the DD panel).; to: Comment on gene classification - This gene should remain as Green rating as there are four unrelated cases and two different variants reported.

PMID:12459588 - Two unrelated families with the same variant (4bp homozygous deletion) and with intellectual disability. Although the cases were thought to be unrelated, they had the same haplotype across the PRSS12 locus, suggesting either distant consanguinity or a founder effect in the Algerian population.

PMID:25529582 - Two unrelated cases with homozygous c.2389C>T/ p.Arg797Cys variants and with severe intellectual disability reported in the Deciphering Developmental Disorders (DDD) study.

In addition, this gene has been associated with intellectual disability in both OMIM (MIM #249500) and Gene2Phenotype (with 'Definitive' rating in the DD panel).
Intellectual disability v5.137 PRSS12 Achchuthan Shanmugasundram changed review comment from: PMID:12459588 - Two unrelated families with the same variant (4bp homozygous deletion) and with intellectual disability. Although the cases were thought to be unrelated, they had the same haplotype across the PRSS12 locus, suggesting either distant consanguinity or a founder effect in the Algerian population.

PMID:25529582 - Two unrelated cases with homozygous c.2389C>T/ p.Arg797Cys variants and with severe intellectual disability reported in the Deciphering Developmental Disorders (DDD) study.

In addition, this gene has been associated with intellectual disability in both OMIM (MIM #249500) and Gene2Phenotype (with 'Definitive' rating in the DD panel).; to: PMID:12459588 - Two unrelated families with the same variant (4bp homozygous deletion) and with intellectual disability. Although the cases were thought to be unrelated, they had the same haplotype across the PRSS12 locus, suggesting either distant consanguinity or a founder effect in the Algerian population.

PMID:25529582 - Two unrelated cases with homozygous c.2389C>T/ p.Arg797Cys variants and with severe intellectual disability reported in the Deciphering Developmental Disorders (DDD) study.

In addition, this gene has been associated with intellectual disability in both OMIM (MIM #249500) and Gene2Phenotype (with 'Definitive' rating in the DD panel).
Intellectual disability v5.137 PRSS12 Achchuthan Shanmugasundram reviewed gene: PRSS12: Rating: GREEN; Mode of pathogenicity: None; Publications: 12459588, 25529582; Phenotypes: Intellectual developmental disorder, autosomal recessive 1, OMIM:249500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: MAN2C1.
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Classified gene: MAN2C1 as Amber List (moderate evidence)
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next major update.
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Gene: man2c1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Classified gene: MAN2C1 as Amber List (moderate evidence)
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next major update.
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Gene: man2c1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Classified gene: MAN2C1 as Amber List (moderate evidence)
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next major update.
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Gene: man2c1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next major update.; to: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN rating at the next major update.
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Classified gene: MAN2C1 as Amber List (moderate evidence)
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next major update.
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Gene: man2c1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Classified gene: MAN2C1 as Amber List (moderate evidence)
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next major update.
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Gene: man2c1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Classified gene: MAN2C1 as Amber List (moderate evidence)
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next major update.
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Gene: man2c1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Classified gene: MAN2C1 as Amber List (moderate evidence)
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next major update.
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Gene: man2c1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Classified gene: MAN2C1 as Amber List (moderate evidence)
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next major update.
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Gene: man2c1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Classified gene: MAN2C1 as Amber List (moderate evidence)
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next major update.
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Gene: man2c1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Classified gene: MAN2C1 as Amber List (moderate evidence)
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next major update.
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Gene: man2c1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Classified gene: MAN2C1 as Amber List (moderate evidence)
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next major update.
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Gene: man2c1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.136 MAN2C1 Achchuthan Shanmugasundram Phenotypes for gene: MAN2C1 were changed from Congenital disorder of deglycosylation 2, OMIM:619775 to Congenital disorder of deglycosylation 2, OMIM:619775
Intellectual disability v5.136 MAN2C1 Achchuthan Shanmugasundram Phenotypes for gene: MAN2C1 were changed from Congenital disorder of deglycosylation 2, OMIM:619775 to Congenital disorder of deglycosylation 2, OMIM:619775
Intellectual disability v5.136 MAN2C1 Achchuthan Shanmugasundram Phenotypes for gene: MAN2C1 were changed from Congenital disorder of deglycosylation 2, OMIM:619775 to Congenital disorder of deglycosylation 2, OMIM:619775
Intellectual disability v5.136 MAN2C1 Achchuthan Shanmugasundram Phenotypes for gene: MAN2C1 were changed from Congenital disorder of deglycosylation 2, OMIM:619775 to Congenital disorder of deglycosylation 2, OMIM:619775
Intellectual disability v5.136 MAN2C1 Achchuthan Shanmugasundram Phenotypes for gene: MAN2C1 were changed from Congenital disorder of deglycosylation 2, OMIM:619775 to Congenital disorder of deglycosylation 2, OMIM:619775
Intellectual disability v5.136 MAN2C1 Achchuthan Shanmugasundram Phenotypes for gene: MAN2C1 were changed from Congenital disorder of deglycosylation 2, OMIM:619775 to Congenital disorder of deglycosylation 2, OMIM:619775
Intellectual disability v5.136 MAN2C1 Achchuthan Shanmugasundram Phenotypes for gene: MAN2C1 were changed from Global developmental delay; Intellectual disability; Abnormality of nervous system morphology; Abnormality of the corpus callosum; Ventriculomegaly; Polymicrogyria; Abnormality of the face; Macrocephaly to Congenital disorder of deglycosylation 2, OMIM:619775
Intellectual disability v5.135 MAN2C1 Achchuthan Shanmugasundram commented on gene: MAN2C1: As reviewed by Konstantinos Varvagiannis, there are three unrelated cases reported with intellectual disability in PMID:35045343.

In addition, this gene has been associated with relevant phenotypes in both OMIM (MIM #619775) and Gene2Phenotype (with 'strong' rating in DD panel).
Intellectual disability v5.135 MAN2C1 Achchuthan Shanmugasundram reviewed gene: MAN2C1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35045343; Phenotypes: Congenital disorder of deglycosylation 2, OMIM:619775; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.135 FAAH2 Achchuthan Shanmugasundram changed review comment from: As reviewed already, there are two cases reported in PMIDs: 25885783 & 34645488. Additional cases were reported in PMIDs: 20655035 & 23352160, however without much clinical details. Hence, the rating should remain amber.; to: As reviewed already, there are two cases reported in PMIDs: 25885783 & 34645488. Additional cases were reported in PMIDs: 20655035 & 23352160, however without much clinical details. Hence, the rating should remain amber.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Intellectual disability v5.135 FAAH2 Achchuthan Shanmugasundram Mode of inheritance for gene: FAAH2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.135 FAAH2 Achchuthan Shanmugasundram Mode of inheritance for gene: FAAH2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.134 FAAH2 Achchuthan Shanmugasundram Mode of inheritance for gene: FAAH2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.135 FAAH2 Achchuthan Shanmugasundram Mode of inheritance for gene: FAAH2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.135 FAAH2 Achchuthan Shanmugasundram Mode of inheritance for gene: FAAH2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.134 FAAH2 Achchuthan Shanmugasundram Mode of inheritance for gene: FAAH2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.134 FAAH2 Achchuthan Shanmugasundram Publications for gene: FAAH2 were set to 25885783; 20655035; 34645488
Intellectual disability v5.134 FAAH2 Achchuthan Shanmugasundram Mode of inheritance for gene: FAAH2 was changed from BIALLELIC, autosomal or pseudoautosomal to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.134 FAAH2 Achchuthan Shanmugasundram Publications for gene: FAAH2 were set to 25885783; 20655035; 34645488
Intellectual disability v5.134 FAAH2 Achchuthan Shanmugasundram Publications for gene: FAAH2 were set to 25885783; 20655035; 34645488
Intellectual disability v5.133 FAAH2 Achchuthan Shanmugasundram Publications for gene: FAAH2 were set to 25885783; 20655035; 34645488
Intellectual disability v5.134 FAAH2 Achchuthan Shanmugasundram Publications for gene: FAAH2 were set to 25885783; 20655035; 34645488
Intellectual disability v5.134 FAAH2 Achchuthan Shanmugasundram Publications for gene: FAAH2 were set to 25885783; 20655035; 34645488
Intellectual disability v5.134 FAAH2 Achchuthan Shanmugasundram Publications for gene: FAAH2 were set to 25885783; 20655035; 34645488
Intellectual disability v5.134 FAAH2 Achchuthan Shanmugasundram Publications for gene: FAAH2 were set to 25885783; 20655035; 34645488
Intellectual disability v5.133 FAAH2 Achchuthan Shanmugasundram Publications for gene: FAAH2 were set to 25885783; 20655035; 34645488
Intellectual disability v5.133 FAAH2 Achchuthan Shanmugasundram Publications for gene: FAAH2 were set to 25885783; 20655035
Intellectual disability v5.133 FAAH2 Achchuthan Shanmugasundram Mode of inheritance for gene: FAAH2 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.133 FAAH2 Achchuthan Shanmugasundram Mode of inheritance for gene: FAAH2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.132 FAAH2 Achchuthan Shanmugasundram Mode of inheritance for gene: FAAH2 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.131 FAAH2 Achchuthan Shanmugasundram reviewed gene: FAAH2: Rating: AMBER; Mode of pathogenicity: None; Publications: 25885783, 34645488; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Childhood solid tumours v4.2 FBXW7 Dmitrijs Rots gene: FBXW7 was added
gene: FBXW7 was added to Childhood solid tumours. Sources: Literature
Mode of inheritance for gene: FBXW7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FBXW7 were set to 30885698
Phenotypes for gene: FBXW7 were set to Developmental delay, hypotonia, and impaired language
Penetrance for gene: FBXW7 were set to Incomplete
Review for gene: FBXW7 was set to GREEN
Added comment: In 30885698 five cases with de novo and truncating variants and childhood tumors are reported. Gene is intolerant to truncating variants (pLI=1). Enough evidence for green rating.
Sources: Literature
Childhood solid tumours v4.2 KDM3B Dmitrijs Rots gene: KDM3B was added
gene: KDM3B was added to Childhood solid tumours. Sources: Literature
Mode of inheritance for gene: KDM3B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KDM3B were set to 30885698; 30929739
Phenotypes for gene: KDM3B were set to Diets-Jongmans syndrome
Review for gene: KDM3B was set to GREEN
Added comment: in 30885698 and 30929739 in total are reported 4 cases with cancer (2 Wilms tumor, 1 AML and 1 HL) AND de novo variants. enough evidence for green rating.
Sources: Literature
Ectodermal dysplasia v3.1 RIPK4 Eleanor Williams Tag Q1_22_rating was removed from gene: RIPK4.
Tag Q1_23_promote_green tag was added to gene: RIPK4.
DDG2P v3.2 DMPK_CTG Eleanor Williams commented on STR: DMPK_CTG: Removed the Q3_21_rating and Q3_21_expert_review tags because this STR is green on other component panels of the Paediatric disorders superpanel and so does not need to be green here.
DDG2P v3.2 DMPK_CTG Eleanor Williams Tag Q3_21_rating was removed from STR: DMPK_CTG.
Tag Q3_21_expert_review was removed from STR: DMPK_CTG.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.17 IRF7 Arina Puzriakova Classified gene: IRF7 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.17 IRF7 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update. At least 7 families reported. Individuals with biallelic variants in the IRF7 gene appear more prone to viral infections of the respiratory tract.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.17 IRF7 Arina Puzriakova Gene: irf7 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.16 IRF7 Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: IRF7.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.16 IRF7 Arina Puzriakova Phenotypes for gene: IRF7 were changed from Severe influenza; Defects in Intrinsic and Innate Immunity; IRF7 deficiency; ?Immunodeficiency 39, 616345; Severe influenza disease to Immunodeficiency 39 , OMIM:616345
Primary immunodeficiency or monogenic inflammatory bowel disease v4.15 COPG1 Arina Puzriakova Publications for gene: COPG1 were set to PMID: 35748970; PMID: 33529166
Primary immunodeficiency or monogenic inflammatory bowel disease v4.14 COPG1 Arina Puzriakova Classified gene: COPG1 as Red List (low evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.14 COPG1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Inga Nartisa. Not yet associated with any phenotype in OMIM or G2P. Only a single family reported to date with a homozygous variant (p.K652E) in this gene (PMID: 33529166). Five affected siblings presented with persistent bacterial and viral infections and defective humoral and cellular immunity. Some functional studies including a mouse model. However, as only a single case has been identified rating as Red for now, awaiting further cases/reports that corroborate this association.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.14 COPG1 Arina Puzriakova Gene: copg1 has been classified as Red List (Low Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.98 ADAMTSL4 Eleanor Williams Mode of inheritance for gene: ADAMTSL4 was changed from to BIALLELIC, autosomal or pseudoautosomal
Dystonia, chorea or related movement disorder, childhood onset v3.8 ARFGEF3 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: ARFGEF3.
Dystonia, chorea or related movement disorder, childhood onset v3.8 ARFGEF3 Achchuthan Shanmugasundram Classified gene: ARFGEF3 as Amber List (moderate evidence)
Dystonia, chorea or related movement disorder, childhood onset v3.8 ARFGEF3 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there are three unrelated cases with monoallelic variants in this gene and with childhood-onset dystonia. Hence, this gene can be promoted to GREEN at the next major update.
Dystonia, chorea or related movement disorder, childhood onset v3.8 ARFGEF3 Achchuthan Shanmugasundram Gene: arfgef3 has been classified as Amber List (Moderate Evidence).
Dystonia, chorea or related movement disorder, childhood onset v3.7 ARFGEF3 Achchuthan Shanmugasundram Phenotypes for gene: ARFGEF3 were changed from Dystonia to early-onset generalized dystonia, MONDO:0100016
Dystonia, chorea or related movement disorder, childhood onset v3.6 ARFGEF3 Achchuthan Shanmugasundram reviewed gene: ARFGEF3: Rating: GREEN; Mode of pathogenicity: None; Publications: 33098801; Phenotypes: early-onset generalized dystonia, MONDO:0100016; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Familial breast cancer v1.18 CDH1 Lauma Freimane reviewed gene: CDH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 36436516; Phenotypes: Lobular breast cancer; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v4.13 CHUK Arina Puzriakova Publications for gene: CHUK were set to PMID: 35748970; PMID: 34533979
Primary immunodeficiency or monogenic inflammatory bowel disease v4.12 CHUK Arina Puzriakova Classified gene: CHUK as Red List (low evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.12 CHUK Arina Puzriakova Added comment: Comment on list classification: New gene added by Inga Nartisa. Biallelic variants are typically associated with Cocoon syndrome (MIM# 613630; definitive in G2P) or Popliteal pterygium syndrome (MIM# 619339), but immune deficits are not known to be associated. Only a single patient with a history of recurrent pneumonias and failure to thrive identified to date with a homozygous variant in this gene (PMID: 34533979). Therefore, rating Red for now, awaiting further cases/reports that corroborate this association.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.12 CHUK Arina Puzriakova Gene: chuk has been classified as Red List (Low Evidence).
Fetal anomalies v3.84 CHUK Arina Puzriakova Phenotypes for gene: CHUK were changed from COCOON SYNDROME to Cocoon syndrome, OMIM:613630; Popliteal pterygium syndrome, Bartsocas-Papas type 2, OMIM:619339
Familial breast cancer v1.18 ATRIP Lauma Freimane gene: ATRIP was added
gene: ATRIP was added to Familial breast cancer. Sources: Literature
Mode of inheritance for gene: ATRIP was set to Unknown
Publications for gene: ATRIP were set to 36977412
Phenotypes for gene: ATRIP were set to Hereditary breast cancer
Review for gene: ATRIP was set to GREEN
gene: ATRIP was marked as current diagnostic
Added comment: Meta-analysis confirms ATRIP role in breast cancer development (https://doi.org/10.1101/2022.06.17.22276537).
Variants in ATRIP are associated with breast cancer susceptibility in the Polish population and UK Biobank.
Sources: Literature
Intellectual disability v5.131 ITPR1 Arina Puzriakova Phenotypes for gene: ITPR1 were changed from Gillespie syndrome 206700 to Gillespie syndrome, OMIM:206700; Spinocerebellar ataxia 15, OMIM:606658; Spinocerebellar ataxia 29, congenital nonprogressive, OMIM:117360
Intellectual disability v5.130 ITPR1 Arina Puzriakova Added comment: Comment on mode of inheritance: Should be updated from 'biallelic' to 'both mono- and biallelic' at the next GMS panel update inline with the review by Tracy Lester. Although not observed in all, some patients do exhibit cognitive deficits which may be an early and severe feature. There are sufficient unrelated cases with heterozygous variants and ID (associated with either Gillespie or SCA) to warrant including this MOI on this panel.
Intellectual disability v5.130 ITPR1 Arina Puzriakova Mode of inheritance for gene: ITPR1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.129 ITPR1 Arina Puzriakova Publications for gene: ITPR1 were set to 22986007
Intellectual disability v5.128 ITPR1 Arina Puzriakova Tag Q2_23_MOI tag was added to gene: ITPR1.
Tag Q2_23_NHS_review tag was added to gene: ITPR1.
Bleeding and platelet disorders v3.2 APOLD1 Arina Puzriakova commented on gene: APOLD1
Fetal anomalies v3.83 BLM Arina Puzriakova Phenotypes for gene: BLM were changed from BLOOM SYNDROME to Bloom syndrome, OMIM:210900
Fanconi anaemia or Bloom syndrome v2.2 BLM Arina Puzriakova Phenotypes for gene: BLM were changed from 210900 Bloom syndrome; Bloom syndrome, 210900 to Bloom syndrome, OMIM:210900
Severe microcephaly v4.12 BLM Arina Puzriakova Phenotypes for gene: BLM were changed from MPD; microcephalic primordial dwarfism; Bloom syndrome, 210900; microcephaly to Bloom syndrome, OMIM:210900
Haematological malignancies cancer susceptibility v4.2 BLM Arina Puzriakova Phenotypes for gene: BLM were changed from Class: BM failure syndrome (typ AR); Bloom syndrome; leukaemia; lymphoma; skin squamous cell; other tumour types; Lymphoma; ALL; MDS; AML; Leukaemia; Carcinomas to Bloom syndrome, OMIM:210900
Childhood solid tumours cancer susceptibility v1.24 BLM Arina Puzriakova Phenotypes for gene: BLM were changed from Bloom Syndrome to Bloom syndrome, OMIM:210900
Primary immunodeficiency or monogenic inflammatory bowel disease v4.11 BLM Arina Puzriakova Phenotypes for gene: BLM were changed from Bloom syndrome, 210900; Immunodeficiency; Short stature, dysmorphic facies, sun-sensitive erythema, marrow failure, leukemia, lymphoma, chromosomal instability; Combined immunodeficiencies with associated or syndromic features to Bloom syndrome, OMIM:210900; Immunodeficiency; Short stature, dysmorphic facies, sun-sensitive erythema, marrow failure, leukemia, lymphoma, chromosomal instability; Combined immunodeficiencies with associated or syndromic features
Childhood solid tumours v4.2 BLM Arina Puzriakova Phenotypes for gene: BLM were changed from Bloom Syndrome; 210900 to Bloom syndrome, OMIM:210900
Insulin resistance (including lipodystrophy) v1.16 BLM Arina Puzriakova Phenotypes for gene: BLM were changed from Bloom syndrome 210900 to Bloom syndrome, OMIM:210900
Intellectual disability v5.128 BLM Arina Puzriakova Phenotypes for gene: BLM were changed from Bloom syndrome, 210900; BLOOM SYNDROME to Bloom syndrome, OMIM:210900
Intellectual disability v5.128 BLM Arina Puzriakova Publications for gene: BLM were set to
Intellectual disability v5.127 BLM Arina Puzriakova reviewed gene: BLM: Rating: ; Mode of pathogenicity: None; Publications: 22514588, 23552953, 36646944; Phenotypes: ; Mode of inheritance: None
Hypogonadotropic hypogonadism (GMS) v3.2 PROKR2 Achchuthan Shanmugasundram Publications for gene: PROKR2 were set to
Intellectual disability v5.127 NSF Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene is now associated with a relevant phenotype in OMIM (MIM #619340), but not in Gene2Phenotype.
Intellectual disability v5.127 NSF Achchuthan Shanmugasundram Phenotypes for gene: NSF were changed from Developmental and epileptic encephalopathy 96, OMIM:619340 to Developmental and epileptic encephalopathy 96, OMIM:619340
Intellectual disability v5.127 NSF Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene is now associated with a relevant phenotype in OMIM (MIM #619340), but not in Gene2Phenotype.
Intellectual disability v5.127 NSF Achchuthan Shanmugasundram Phenotypes for gene: NSF were changed from Developmental and epileptic encephalopathy 96, OMIM:619340 to Developmental and epileptic encephalopathy 96, OMIM:619340
Intellectual disability v5.127 NSF Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene is now associated with a relevant phenotype in OMIM (MIM #619340), but not in Gene2Phenotype.
Intellectual disability v5.127 NSF Achchuthan Shanmugasundram Phenotypes for gene: NSF were changed from Developmental and epileptic encephalopathy 96, OMIM:619340 to Developmental and epileptic encephalopathy 96, OMIM:619340
Intellectual disability v5.127 NSF Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.127 NSF Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene is now associated with a relevant phenotype in OMIM (MIM #619340), but not in Gene2Phenotype.
Intellectual disability v5.127 NSF Achchuthan Shanmugasundram Phenotypes for gene: NSF were changed from Developmental and epileptic encephalopathy 96, OMIM:619340 to Developmental and epileptic encephalopathy 96, OMIM:619340
Intellectual disability v5.126 NSF Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.126 NSF Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene is now associated with a relevant phenotype in OMIM (MIM #619340), but not in Gene2Phenotype.
Intellectual disability v5.126 NSF Achchuthan Shanmugasundram Phenotypes for gene: NSF were changed from Developmental and epileptic encephalopathy 96, OMIM:619340 to Developmental and epileptic encephalopathy 96, OMIM:619340
Intellectual disability v5.126 NSF Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene is now associated with a relevant phenotype in OMIM (MIM #619340), but not in Gene2Phenotype.
Intellectual disability v5.126 NSF Achchuthan Shanmugasundram Phenotypes for gene: NSF were changed from Seizures; EEG with burst suppression; Global developmental delay; Intellectual disability to Developmental and epileptic encephalopathy 96, OMIM:619340
Intellectual disability v5.125 NSF Achchuthan Shanmugasundram reviewed gene: NSF: Rating: RED; Mode of pathogenicity: None; Publications: 36645181; Phenotypes: Developmental and epileptic encephalopathy 96, OMIM:619340; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.125 NSF Achchuthan Shanmugasundram Publications for gene: NSF were set to 31675180; 36645181
Intellectual disability v5.125 NSF Achchuthan Shanmugasundram Publications for gene: NSF were set to 31675180
Early onset or syndromic epilepsy v4.39 NSF Achchuthan Shanmugasundram Phenotypes for gene: NSF were changed from Developmental and epileptic encephalopathy 96, OMIM:619340 to Developmental and epileptic encephalopathy 96, OMIM:619340
Early onset or syndromic epilepsy v4.39 NSF Achchuthan Shanmugasundram Phenotypes for gene: NSF were changed from Seizures; EEG with burst suppression; Global developmental delay; Intellectual disability to Developmental and epileptic encephalopathy 96, OMIM:619340
Early onset or syndromic epilepsy v4.38 NSF Achchuthan Shanmugasundram Publications for gene: NSF were set to 31675180; 36645181
Early onset or syndromic epilepsy v4.38 NSF Achchuthan Shanmugasundram Publications for gene: NSF were set to 31675180
Early onset or syndromic epilepsy v4.37 NSF Achchuthan Shanmugasundram edited their review of gene: NSF: Changed rating: AMBER
Early onset or syndromic epilepsy v4.37 NSF Achchuthan Shanmugasundram changed review comment from: PMID:36645181 describes the two previously reported cases from PMID:31675180. The third case reported had a very mild phenotype and did not present with epilepsy and had normal development. Hence, this gene should remain AMBER.; to: PMID:36645181 describes the two previously reported cases from PMID:31675180. The third case reported had a very mild phenotype and did not present with epilepsy and had normal development. Hence, this gene should remain AMBER.

This gene has now been associated with relevant phenotype in OMIM (MIM #619340), but not in Gene2Phenotype.
Early onset or syndromic epilepsy v4.37 NSF Achchuthan Shanmugasundram reviewed gene: NSF: Rating: GREEN; Mode of pathogenicity: None; Publications: 36645181; Phenotypes: Developmental and epileptic encephalopathy 96, OMIM:619340; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Severe microcephaly v4.11 LHX2 Sarah Leigh Tag Q2_23_promote_green was removed from gene: LHX2.
Severe microcephaly v4.11 LHX2 Sarah Leigh changed review comment from: Not associated with a phenotype in OMIM, Gen2Phen or MONDO. PMID: 37057675 reports 17 predominanly de novo LHX2 variants in a panel of patients with a variable neurodevelopmental disorder. Haploinsufficiency and functional studies are supportive of a loss-of-function pathogenic action of the reported LHX2 variants.
Sources: Literature; to: Not associated with a phenotype in OMIM, Gen2Phen or MONDO. PMID: 37057675 reports 17 predominantly de novo LHX2 variants in a panel of patients with a variable neurodevelopmental disorder. Haploinsufficiency and functional studies are supportive of a loss-of-function pathogenic action of the reported LHX2 variants.
Seven out of the ten cases reported in table 1 (PMID: 37057675) are listed as having microcephaly, however, due to lack of clinical information, these cases cannot be classified as severe (personal communication with the author, Christiane Zweier).
Sources: Literature
Severe microcephaly v4.11 LHX2 Sarah Leigh Deleted their comment
Severe microcephaly v4.11 LHX2 Sarah Leigh edited their review of gene: LHX2: Changed rating: AMBER
Severe microcephaly v4.11 LHX2 Sarah Leigh Entity copied from Intellectual disability - microarray and sequencing v5.124
Severe microcephaly v4.11 LHX2 Sarah Leigh gene: LHX2 was added
gene: LHX2 was added to Severe microcephaly. Sources: Literature,Expert Review Amber
Q2_23_promote_green tags were added to gene: LHX2.
Mode of inheritance for gene: LHX2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: LHX2 were set to 37057675
Phenotypes for gene: LHX2 were set to neurodevelopmental disorder
Congenital myaesthenic syndrome v4.3 SLC5A7 Achchuthan Shanmugasundram Publications for gene: SLC5A7 were set to 27569547; 23141292; 26786006
Early onset or syndromic epilepsy v4.37 CPA6 Ian Berry reviewed gene: CPA6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital myaesthenic syndrome v4.2 DOK7 Achchuthan Shanmugasundram Publications for gene: DOK7 were set to 16917026; 17452375; 22661499; 18626973
Hereditary neuropathy or pain disorder v3.26 RFC1 Sarah Leigh Publications for gene: RFC1 were set to 30926972; 31824583; 32851396; 32582864; 33969391
Hereditary ataxia, adult onset v4.10 RFC1 Sarah Leigh Publications for gene: RFC1 were set to 30926972; 31824583; 32851396; 32582864; 33969391
Early onset or syndromic epilepsy v4.37 ENTPD1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: ENTPD1.
Early onset or syndromic epilepsy v4.37 ENTPD1 Achchuthan Shanmugasundram Classified gene: ENTPD1 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.37 ENTPD1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Konstantinos Varvagiannis, there are seven unrelated cases with epilepsy. Hence, this gene can be promoted to GREEN rating in the next major update.
Early onset or syndromic epilepsy v4.37 ENTPD1 Achchuthan Shanmugasundram Gene: entpd1 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.36 ENTPD1 Achchuthan Shanmugasundram reviewed gene: ENTPD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35471564; Phenotypes: Spastic paraplegia 64, autosomal recessive, OMIM:15683; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - childhood onset v3.10 ENTPD1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: ENTPD1.
White matter disorders and cerebral calcification - childhood onset v3.10 ENTPD1 Achchuthan Shanmugasundram Classified gene: ENTPD1 as Amber List (moderate evidence)
White matter disorders and cerebral calcification - childhood onset v3.10 ENTPD1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (>10 unrelated cases) for this gene to be promoted to GREEN in the next major update.
White matter disorders and cerebral calcification - childhood onset v3.10 ENTPD1 Achchuthan Shanmugasundram Gene: entpd1 has been classified as Amber List (Moderate Evidence).
White matter disorders and cerebral calcification - childhood onset v3.9 ENTPD1 Achchuthan Shanmugasundram changed review comment from: PMID:35471564 reported 27 cases from 17 families with a complex childhood-onset neurodevelopmental disorder characterised by intellectual disability/ developmental delay and spastic paraplegia in all individuals, white matter abnormalities in 12 individuals and epilepsy in 7 individuals.
Sources: Literature; to: PMID:35471564 reported 27 cases from 17 families with a complex childhood-onset neurodevelopmental disorder characterised by intellectual disability/ developmental delay and spastic paraplegia in all individuals, white matter abnormalities in 12 individuals (from 9 families) and epilepsy in 7 individuals.

In addition, it was also reviewed here that two unrelated families were previously reported with white matter abnormalities.
Sources: Literature
Intellectual disability v5.124 ENTPD1 Achchuthan Shanmugasundram Publications for gene: ENTPD1 were set to 21937992; 24482476; 29691679; 30652007; 35471564; 35758610
Intellectual disability v5.124 ENTPD1 Achchuthan Shanmugasundram Publications for gene: ENTPD1 were set to 21937992; 24482476; 29691679; 30652007; 35471564; 35758610
Intellectual disability v5.124 ENTPD1 Achchuthan Shanmugasundram Publications for gene: ENTPD1 were set to 21937992; 24482476; 29691679; 30652007; 35471564; 35758610
Intellectual disability v5.124 ENTPD1 Achchuthan Shanmugasundram Publications for gene: ENTPD1 were set to 21937992; 24482476; 29691679; 30652007; 35471564
Intellectual disability v5.123 ENTPD1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: ENTPD1.
Intellectual disability v5.123 ENTPD1 Achchuthan Shanmugasundram changed review comment from: As reviewed by Konstantinos Varvagiannis, PMID:35471564 reported 27 cases from 17 families with a complex childhood-onset neurodevelopmental disorder characterised by intellectual disability/ developmental delay and spastic paraplegia in all individuals, white matter abnormalities in 12 individuals and epilepsy in 7 individuals.

In addition, this gene has been associated with autosomal recessive intellectual developmental disorder in Gene2phenotype with 'limited' rating and ID has been included as part of the SPG64 phenotype in OMIM. ; to: As reviewed by Konstantinos Varvagiannis, PMID:35471564 reported 27 cases from 17 families with biallelic variants in ENTPD1 and with a complex childhood-onset neurodevelopmental disorder characterised by intellectual disability/ developmental delay and spastic paraplegia in all individuals, white matter abnormalities in 12 individuals and epilepsy in 7 individuals.

PMID:35758610 reported two siblings with biallelic variants in ENTPD1. The proband was mildly intellectually disabled and her brother was moderately clinically disabled based on clinical observations.

In addition, this gene has been associated with autosomal recessive intellectual developmental disorder in Gene2phenotype with 'limited' rating and ID has been included as part of the SPG64 phenotype in OMIM.
Intellectual disability v5.123 COASY Sarah Leigh Phenotypes for gene: COASY were changed from Neurodegeneration with brain iron accumulation 6, OMIM:615643; neurodegeneration with brain iron accumulation 6, MONDO:0014290 to Neurodegeneration with brain iron accumulation 6, OMIM:615643; neurodegeneration with brain iron accumulation 6, MONDO:0014290; Pontocerebellar hypoplasia, type 12, OMIM:618266; pontocerebellar hypoplasia, type 12, MONDO:0032643
Intellectual disability v5.122 ENTPD1 Achchuthan Shanmugasundram edited their review of gene: ENTPD1: Changed publications to: 35471564, 35758610
Arthrogryposis v5.9 COASY Sarah Leigh Phenotypes for gene: COASY were changed from Pontocerebellar hypoplasia, type 12, OMIM:618266; pontocerebellar hypoplasia, type 12, MONDO:0032643 to Pontocerebellar hypoplasia, type 12, OMIM:618266; pontocerebellar hypoplasia, type 12, MONDO:0032643
Structural basal ganglia disorders v1.38 COASY Sarah Leigh Phenotypes for gene: COASY were changed from Neurodegeneration with brain iron accumulation 6 615643 to Neurodegeneration with brain iron accumulation 6, OMIM:615643; neurodegeneration with brain iron accumulation 6, MONDO:0014290
Ataxia and cerebellar anomalies - childhood onset v4.10 COASY Sarah Leigh Phenotypes for gene: COASY were changed from Pontocerebellar hypoplasia, type 12, OMIM:618266; pontocerebellar hypoplasia, type 12, MONDO:0032643 to Neurodegeneration with brain iron accumulation 6, OMIM:615643; neurodegeneration with brain iron accumulation 6, MONDO:0014290; Pontocerebellar hypoplasia, type 12, OMIM:618266; pontocerebellar hypoplasia, type 12, MONDO:0032643
Early onset dystonia v1.135 COASY Sarah Leigh Phenotypes for gene: COASY were changed from Neurodegeneration with brain iron accumulation 6; COASY protein-associated neurodegeneration to Neurodegeneration with brain iron accumulation 6, OMIM:615643; neurodegeneration with brain iron accumulation 6, MONDO:0014290
Ataxia and cerebellar anomalies - childhood onset v4.9 COASY Sarah Leigh Phenotypes for gene: COASY were changed from Severe prenatal onset pontocerebellar hypoplasia, microcephaly, arthrogryposis to Pontocerebellar hypoplasia, type 12, OMIM:618266; pontocerebellar hypoplasia, type 12, MONDO:0032643
Mitochondrial disorders v4.38 COASY Sarah Leigh Classified gene: COASY as Amber List (moderate evidence)
Mitochondrial disorders v4.38 COASY Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Mitochondrial disorders v4.38 COASY Sarah Leigh Gene: coasy has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v4.37 COASY Sarah Leigh Tag Q2_23_promote_green tag was added to gene: COASY.
Intellectual disability v5.122 COASY Sarah Leigh Publications for gene: COASY were set to 24360804
Parkinson Disease and Complex Parkinsonism v1.114 COASY Sarah Leigh Publications for gene: COASY were set to 28489334; 24360804
Arthrogryposis v5.8 COASY Sarah Leigh Publications for gene: COASY were set to 30089828; 24360804
Structural basal ganglia disorders v1.37 COASY Sarah Leigh Publications for gene: COASY were set to 27021474; 24360804
Ataxia and cerebellar anomalies - childhood onset v4.8 COASY Sarah Leigh Publications for gene: COASY were set to 24360804; 30089828
Early onset dystonia v1.134 COASY Sarah Leigh Publications for gene: COASY were set to 27021474
Mitochondrial disorders v4.37 COASY Sarah Leigh Publications for gene: COASY were set to 11980892; 25778941; 24360804; 28489334; 30089828; 36495139
White matter disorders and cerebral calcification - childhood onset v3.9 ENTPD1 Achchuthan Shanmugasundram gene: ENTPD1 was added
gene: ENTPD1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Literature
Mode of inheritance for gene: ENTPD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ENTPD1 were set to 35471564
Phenotypes for gene: ENTPD1 were set to Spastic paraplegia 64, autosomal recessive, OMIM:615683
Review for gene: ENTPD1 was set to GREEN
Added comment: PMID:35471564 reported 27 cases from 17 families with a complex childhood-onset neurodevelopmental disorder characterised by intellectual disability/ developmental delay and spastic paraplegia in all individuals, white matter abnormalities in 12 individuals and epilepsy in 7 individuals.
Sources: Literature
Intellectual disability v5.121 ENTPD1 Achchuthan Shanmugasundram changed review comment from: As reviewed by Konstantinos Varvagiannis, PMID35471564 reported 27 cases from 17 families with a complex childhood-onset neurodevelopmental disorder characterised by intellectual disability/ developmental delay and spastic paraplegia in all individuals, white matter abnormalities in 12 individuals and epilepsy in 7 individuals.

In addition, this gene has been associated with autosomal recessive intellectual developmental disorder in Gene2phenotype with 'limited' rating and ID has been included as part of the SPG64 phenotype in OMIM. ; to: As reviewed by Konstantinos Varvagiannis, PMID:35471564 reported 27 cases from 17 families with a complex childhood-onset neurodevelopmental disorder characterised by intellectual disability/ developmental delay and spastic paraplegia in all individuals, white matter abnormalities in 12 individuals and epilepsy in 7 individuals.

In addition, this gene has been associated with autosomal recessive intellectual developmental disorder in Gene2phenotype with 'limited' rating and ID has been included as part of the SPG64 phenotype in OMIM.
Mitochondrial disorders v4.36 COASY Sarah Leigh Publications for gene: COASY were set to 25778941; 24360804; 30089828; 28489334
Mitochondrial disorders v4.35 COASY Sarah Leigh edited their review of gene: COASY: Added comment: COASY variants are associated with Neurodegeneration with brain iron accumulation 6 (OMIM: 615643) and as definitive Gen2Phen gene for neurodegeneration with brain iron accumulation and also with Pontocerebellar hypoplasia, type 12, OMIM:618266.
PMID: 24360804 & 28489334 report three COASY variants in three unrelated cases of OMIM: 615643, with supportive functional studies presented (PMID: 24360804). PMID: 30089828 report two COASY variants in two unrelated cases of OMIM:618266, with in vitro functional studies revealing an absence of COASY-protein. A further homozygous COASY variant has been reported in two sibs with a novel neonatal-onset progressive neurodegenerative disorder with striking brain MRI findings (PMID: 36495139).
It has been established that the COASY protein - coenzyme A synthase - is associated with the outer mitochondrial membrane (PMID: 11980892, 24360804).; Changed rating: GREEN
Intellectual disability v5.121 ENTPD1 Achchuthan Shanmugasundram Classified gene: ENTPD1 as Amber List (moderate evidence)
Intellectual disability v5.121 ENTPD1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to Green rating at the next major update.
Intellectual disability v5.121 ENTPD1 Achchuthan Shanmugasundram Gene: entpd1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.120 ENTPD1 Achchuthan Shanmugasundram changed review comment from: As reviewed by Konstantinos Varvagiannis, PMID35471564 reported 27 cases from 17 families with a complex childhood-onset neurodevelopmental disorder characterised by intellectual disability/ developmental delay and spastic paraplegia in all individuals, white matter abnormalities in 12 individuals and epilepsy in 7 individuals.

In addition, this gene has been associated with autosomal recessive intellectual developmental disorder in Gene2phenotype with 'limited' rating and ID has been includes as part of the SPG64 phenotype in OMIM. ; to: As reviewed by Konstantinos Varvagiannis, PMID35471564 reported 27 cases from 17 families with a complex childhood-onset neurodevelopmental disorder characterised by intellectual disability/ developmental delay and spastic paraplegia in all individuals, white matter abnormalities in 12 individuals and epilepsy in 7 individuals.

In addition, this gene has been associated with autosomal recessive intellectual developmental disorder in Gene2phenotype with 'limited' rating and ID has been included as part of the SPG64 phenotype in OMIM.
Intellectual disability v5.120 ENTPD1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Konstantinos Varvagiannis, PMID35471564 reported 27 cases from 17 families with a complex childhood-onset neurodevelopmental disorder characterised by intellectual disability/ developmental delay and spastic paraplegia in all individuals, white matter abnormalities in 12 individuals and epilepsy in 7 individuals. Hence, this gene can be promoted to Green in the next major update.; to: As reviewed by Konstantinos Varvagiannis, PMID35471564 reported 27 cases from 17 families with a complex childhood-onset neurodevelopmental disorder characterised by intellectual disability/ developmental delay and spastic paraplegia in all individuals, white matter abnormalities in 12 individuals and epilepsy in 7 individuals.

In addition, this gene has been associated with autosomal recessive intellectual developmental disorder in Gene2phenotype with 'limited' rating and ID has been includes as part of the SPG64 phenotype in OMIM.
Intellectual disability v5.120 ENTPD1 Achchuthan Shanmugasundram Publications for gene: ENTPD1 were set to 21937992; 24482476; 29691679; 30652007; 35471564
Intellectual disability v5.120 ENTPD1 Achchuthan Shanmugasundram Publications for gene: ENTPD1 were set to 21937992; 24482476; 29691679; 30652007; 35471564
Intellectual disability v5.120 ENTPD1 Achchuthan Shanmugasundram Publications for gene: ENTPD1 were set to 21937992; 24482476; 29691679; 30652007; 35471564
Intellectual disability v5.120 ENTPD1 Achchuthan Shanmugasundram Publications for gene: ENTPD1 were set to 21937992; 24482476; 29691679; 30652007; 35471564
Intellectual disability v5.120 ENTPD1 Achchuthan Shanmugasundram Publications for gene: ENTPD1 were set to 21937992; 24482476; 29691679; 30652007
Intellectual disability v5.119 ENTPD1 Achchuthan Shanmugasundram Classified gene: ENTPD1 as Amber List (moderate evidence)
Intellectual disability v5.119 ENTPD1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Konstantinos Varvagiannis, PMID35471564 reported 27 cases from 17 families with a complex childhood-onset neurodevelopmental disorder characterised by intellectual disability/ developmental delay and spastic paraplegia in all individuals, white matter abnormalities in 12 individuals and epilepsy in 7 individuals. Hence, this gene can be promoted to Green in the next major update.
Intellectual disability v5.119 ENTPD1 Achchuthan Shanmugasundram Gene: entpd1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.118 ENTPD1 Achchuthan Shanmugasundram reviewed gene: ENTPD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35471564; Phenotypes: Spastic paraplegia 64, autosomal recessive, OMIM:615683; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v4.10 LAMP2 Achchuthan Shanmugasundram Tag Q2_23_NHS_review tag was added to gene: LAMP2.
Retinal disorders v4.10 LAMP2 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: LAMP2.
Retinal disorders v4.10 LAMP2 Achchuthan Shanmugasundram Phenotypes for gene: LAMP2 were changed from Pigmentary retinopathy to Pigmentary retinopathy; Danon disease, OMIM:300257
Retinal disorders v4.9 LAMP2 Achchuthan Shanmugasundram Publications for gene: LAMP2 were set to (PMID: 16751040; 32533651; 36288619; 22290069; 32890081; 26398689)
Retinal disorders v4.8 LAMP2 Achchuthan Shanmugasundram Classified gene: LAMP2 as Amber List (moderate evidence)
Retinal disorders v4.8 LAMP2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Siying Lin (Moorfields Eye Hospital), there is sufficient evidence for this gene to be promoted to GREEN rating at the next GMS update.
Retinal disorders v4.8 LAMP2 Achchuthan Shanmugasundram Gene: lamp2 has been classified as Amber List (Moderate Evidence).
Retinal disorders v4.7 LAMP2 Achchuthan Shanmugasundram reviewed gene: LAMP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 16751040, 22290069, 26398689, 32533651, 32890081, 36288619; Phenotypes: Danon disease, OMIM:300257; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.97 SMAD3 Achchuthan Shanmugasundram Publications for gene: SMAD3 were set to 20301312; 29392890; 31569402; 32935439
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.96 SMAD3 Achchuthan Shanmugasundram edited their review of gene: SMAD3: Changed publications to: 29392890, 31569402, 32935439, 36980886; Changed phenotypes to: Loeys-Dietz syndrome 3, OMIM:613795
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.96 SMAD3 Achchuthan Shanmugasundram changed review comment from: PMID:29392890 - It has been reviewed in this publication that craniosynostosis has only been reported once in a SMAD3 patient. But, no reference was given.

PMID:31569402 - Dolichocephaly has been reported in patients. However, it is not clear whether craniosynostosis has been present in these cases.

PMID:32935439 - One case of LDS with biallelic variants presented with craniosynostosis.

PMID:36980886 - one craniosynostosi case with splicing variant in SMAD3 from the cohort of 617 individuals.

This gene has been associated with LDS in OMIM (MIM #613795) and Gene2Phenotype (with 'definitive' rating in DD panel). However, craniosynostosis was not reported as part of phenotypes in OMIM.; to: PMID:29392890 - It has been reviewed in this publication that craniosynostosis has only been reported once in a SMAD3 patient. But, no reference was given.

PMID:31569402 - Dolichocephaly has been reported in patients. However, it is not clear whether craniosynostosis has been present in these cases.

PMID:32935439 - One case of LDS with biallelic variants presented with craniosynostosis.

PMID:36980886 - one craniosynostosi case with splicing variant in SMAD3 from the cohort of 617 individuals.

This gene has been associated with LDS in OMIM (MIM #613795) and Gene2Phenotype (with 'definitive' rating in DD panel). However, craniosynostosis was not reported as part of this phenotype in OMIM.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.96 SMAD3 Achchuthan Shanmugasundram reviewed gene: SMAD3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v3.25 RFC1 Joseph Shaw reviewed gene: RFC1: Rating: GREEN; Mode of pathogenicity: Other; Publications: 35883251, 36250766, 36289003, 36524104, 36478048; Phenotypes: Neuropathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v3.25 Eleanor Williams Panel version 3.24 has been signed off on 2023-05-15
Hereditary neuropathy or pain disorder v3.24 Eleanor Williams Panel name changed from Hereditary neuropathy or pain disorder - NOT PMP22 copy number to Hereditary neuropathy or pain disorder
Hereditary neuropathy or pain disorder v3.23 Eleanor Williams List of related panels changed from Hereditary neuropathy NOT PMP22 copy number; R78 to Hereditary neuropathy NOT PMP22 copy number; Hereditary neuropathy or pain disorder - NOT PMP22 copy number; R78
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.96 AXIN2 Achchuthan Shanmugasundram Phenotypes for gene: AXIN2 were changed from Oligodontia-colorectal cancer syndrome, OMIM:608615 to Oligodontia-colorectal cancer syndrome, OMIM:608615; craniosynostosis, MONDO:0015469
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.95 AXIN2 Achchuthan Shanmugasundram Publications for gene: AXIN2 were set to
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.94 AXIN2 Achchuthan Shanmugasundram Mode of inheritance for gene: AXIN2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.93 AXIN2 Achchuthan Shanmugasundram Classified gene: AXIN2 as Amber List (moderate evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.93 AXIN2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Rebecca Tooze (University of Oxford), there is one case and supporting evidence from mouse models. Hence, this gene should be rated AMBER.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.93 AXIN2 Achchuthan Shanmugasundram Gene: axin2 has been classified as Amber List (Moderate Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.92 AXIN2 Achchuthan Shanmugasundram reviewed gene: AXIN2: Rating: AMBER; Mode of pathogenicity: None; Publications: 15790973, 30088857, 30976280, 34134783; Phenotypes: craniosynostosis, MONDO:0015469; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.92 SH3PXD2B Achchuthan Shanmugasundram commented on gene: SH3PXD2B: PMID:23140272 reported a family of three siblings with homozygous variants in SH3PXD2B and two of them presented with craniosynostosis.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.92 SH3PXD2B Achchuthan Shanmugasundram reviewed gene: SH3PXD2B: Rating: RED; Mode of pathogenicity: None; Publications: 23140272; Phenotypes: Frank-ter Haar syndrome, OMIM:249420; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.92 SPRY1 Achchuthan Shanmugasundram Classified gene: SPRY1 as Amber List (moderate evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.92 SPRY1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Rebecca Tooze (University of Oxford), there is one case and supporting functional evidence. Hence, this gene should be rated AMBER.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.92 SPRY1 Achchuthan Shanmugasundram Gene: spry1 has been classified as Amber List (Moderate Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.91 SPRY1 Achchuthan Shanmugasundram Phenotypes for gene: SPRY1 were changed from to craniosynostosis, MONDO:0015469
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.90 SPRY1 Achchuthan Shanmugasundram Publications for gene: SPRY1 were set to PMID36543535
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.89 SPRY1 Achchuthan Shanmugasundram Publications for gene: SPRY1 were set to PMID36543535
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.89 SPRY1 Achchuthan Shanmugasundram Publications for gene: SPRY1 were set to PMID: 36543535
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.88 SPRY1 Achchuthan Shanmugasundram Publications for gene: SPRY1 were set to PMID: 36543535
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.87 SPRY1 Achchuthan Shanmugasundram reviewed gene: SPRY1: Rating: AMBER; Mode of pathogenicity: None; Publications: 36543535; Phenotypes: craniosynostosis, MONDO:0015469; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.87 RSPRY1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN rating in the next GMS update.; to: Comment on list classification: There is sufficient evidence (3 unrelated cases) for this gene to be promoted to GREEN rating in the next GMS update.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.87 RSPRY1 Achchuthan Shanmugasundram changed review comment from: As reviewed by Rebecca Tooze, craniosynostosis was reported in a family of four affected individuals identified with homozygous variants in RSPRY1 from PMID:26365341, and in three out of four affected individuals from a family and another unrelated individual with RSPRY1 variants from PMID:30063090. Although the phenotype is not fully penetrant from the family of four cases from PMID:30063090, this gene can be rated GREEN on the basis of the presence of phenotype in three unrelated cases and the phenotype being fully penetrant from the family reported in PMID:26365341.

This gene has been associated with relevant phenotypes in both OMIM (MIM #616723) and Gene2Phenotype (with 'strong' rating in the DD panel).; to: As reviewed by Rebecca Tooze, craniosynostosis was reported in a family of four affected individuals identified with homozygous variants in RSPRY1 from PMID:26365341, and in three out of four affected individuals from a family and another unrelated individual with RSPRY1 variants from PMID:30063090.

This gene has been associated with relevant phenotypes in both OMIM (MIM #616723) and Gene2Phenotype (with 'strong' rating in the DD panel).
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.87 RSPRY1 Achchuthan Shanmugasundram Classified gene: RSPRY1 as Amber List (moderate evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.87 RSPRY1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN rating in the next GMS update.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.87 RSPRY1 Achchuthan Shanmugasundram Gene: rspry1 has been classified as Amber List (Moderate Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.86 RSPRY1 Achchuthan Shanmugasundram changed review comment from: As reviewed by Rebecca Tooze, craniosynostosis was reported in a family of four affected individuals identified with homozygous variants in RSPRY1 from PMID:26365341, and in three out of four affected individuals from a family and another unrelated individual with RSPRY1 variants from PMID:30063090. Although the phenotype is not fully penetrant from the family of four cases from PMID:30063090, this gene can be rated GREEN on the basis of the presence of phenotype in three unrelated cases and the phenotype being fully penetrant from the family reported in PMID:26365341.; to: As reviewed by Rebecca Tooze, craniosynostosis was reported in a family of four affected individuals identified with homozygous variants in RSPRY1 from PMID:26365341, and in three out of four affected individuals from a family and another unrelated individual with RSPRY1 variants from PMID:30063090. Although the phenotype is not fully penetrant from the family of four cases from PMID:30063090, this gene can be rated GREEN on the basis of the presence of phenotype in three unrelated cases and the phenotype being fully penetrant from the family reported in PMID:26365341.

This gene has been associated with relevant phenotypes in both OMIM (MIM #616723) and Gene2Phenotype (with 'strong' rating in the DD panel).
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.86 RSPRY1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: RSPRY1.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.86 RSPRY1 Achchuthan Shanmugasundram Phenotypes for gene: RSPRY1 were changed from to Spondyloepimetaphyseal dysplasia, Faden-Alkuraya type, OMIM:616723
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.85 RSPRY1 Achchuthan Shanmugasundram Publications for gene: RSPRY1 were set to
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.84 RSPRY1 Achchuthan Shanmugasundram Mode of inheritance for gene: RSPRY1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.83 RSPRY1 Achchuthan Shanmugasundram Classified gene: RSPRY1 as Amber List (moderate evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.83 RSPRY1 Achchuthan Shanmugasundram Gene: rspry1 has been classified as Amber List (Moderate Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.82 RSPRY1 Achchuthan Shanmugasundram changed review comment from: As reviewed by Rebecca Tooze, craniosynostosis was reported in a family of four affected individuals identified with homozygous variants in RSPRY1 from PMID:26365341, and in three out of four affected individuals from a family and another unrelated individual with RSPRY1 variants from PMID:30063090. Although the phenotype is not fully penetrant from the family of four cases from PMID:30063090, this gene can be rated GREEN on the basis of the presence of phenotype in three unrelated cases.; to: As reviewed by Rebecca Tooze, craniosynostosis was reported in a family of four affected individuals identified with homozygous variants in RSPRY1 from PMID:26365341, and in three out of four affected individuals from a family and another unrelated individual with RSPRY1 variants from PMID:30063090. Although the phenotype is not fully penetrant from the family of four cases from PMID:30063090, this gene can be rated GREEN on the basis of the presence of phenotype in three unrelated cases and the phenotype being fully penetrant from the family reported in PMID:26365341.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.82 RSPRY1 Achchuthan Shanmugasundram edited their review of gene: RSPRY1: Changed rating: GREEN
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.82 RSPRY1 Achchuthan Shanmugasundram reviewed gene: RSPRY1: Rating: AMBER; Mode of pathogenicity: None; Publications: 26365341, 30063090; Phenotypes: Spondyloepimetaphyseal dysplasia, Faden-Alkuraya type, OMIM:616723; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bleeding and platelet disorders v3.2 APOLD1 Carl Fratter reviewed gene: APOLD1: Rating: AMBER; Mode of pathogenicity: None; Publications: PIMD: 35638551; Phenotypes: Bleeding disorder; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.82 OGT Achchuthan Shanmugasundram Classified gene: OGT as Amber List (moderate evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.82 OGT Achchuthan Shanmugasundram Added comment: Comment on list classification: As there are only two cases reported so far, this gene should be rated AMBER.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.82 OGT Achchuthan Shanmugasundram Gene: ogt has been classified as Amber List (Moderate Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.81 OGT Achchuthan Shanmugasundram Mode of inheritance for gene: OGT was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.80 OGT Achchuthan Shanmugasundram Publications for gene: OGT were set to
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.79 OGT Achchuthan Shanmugasundram Phenotypes for gene: OGT were changed from to Intellectual developmental disorder, X-linked 106, OMIM:300997
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.78 OGT Achchuthan Shanmugasundram reviewed gene: OGT: Rating: AMBER; Mode of pathogenicity: None; Publications: 32530565, 34429528; Phenotypes: Intellectual developmental disorder, X-linked 106, OMIM:300997; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.78 IRX5 Achchuthan Shanmugasundram changed review comment from: PMID:22581230 - One family with three cases presenting with craniosynostosis.
PMID:29168297 - one case with craniosynostosis.; to: PMID:22581230 - One family with three cases presenting with craniosynostosis.
PMID:29168297 - one case with craniosynostosis.

This gene has been associated with relevant phenotypes in both OMIM (MIM #611174) and Gene2Phenotype (with 'strong' rating in the DD panel).
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.78 IRX5 Achchuthan Shanmugasundram Classified gene: IRX5 as Amber List (moderate evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.78 IRX5 Achchuthan Shanmugasundram Added comment: Comment on list classification: As there are only two unrelated cases, this gene should be rated AMBER.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.78 IRX5 Achchuthan Shanmugasundram Gene: irx5 has been classified as Amber List (Moderate Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.77 IRX5 Achchuthan Shanmugasundram Phenotypes for gene: IRX5 were changed from Hamamy syndrome to Hamamy syndrome, OMIM:611174
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.76 IRX5 Achchuthan Shanmugasundram Publications for gene: IRX5 were set to 22581230
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.75 IRX5 Achchuthan Shanmugasundram edited their review of gene: IRX5: Changed rating: AMBER
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.75 IRX5 Achchuthan Shanmugasundram reviewed gene: IRX5: Rating: GREEN; Mode of pathogenicity: None; Publications: 22581230, 29168297; Phenotypes: Hamamy syndrome, OMIM:611174; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.75 IFT43 Achchuthan Shanmugasundram Publications for gene: IFT43 were set to
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.74 IFT43 Achchuthan Shanmugasundram Mode of inheritance for gene: IFT43 was changed from to BIALLELIC, autosomal or pseudoautosomal
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.73 IFT43 Achchuthan Shanmugasundram reviewed gene: IFT43: Rating: RED; Mode of pathogenicity: None; Publications: 21378380; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.73 IFT140 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: IFT140.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.73 IFT140 Achchuthan Shanmugasundram Publications for gene: IFT140 were set to 27874174; 28288023; 32007091
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.72 IFT140 Achchuthan Shanmugasundram Classified gene: IFT140 as Amber List (moderate evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.72 IFT140 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (at least 3 cases) for this gene to be promoted to GREEN rating in the next GMS update.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.72 IFT140 Achchuthan Shanmugasundram Gene: ift140 has been classified as Amber List (Moderate Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.71 IFT140 Achchuthan Shanmugasundram edited their review of gene: IFT140: Added comment: PMID:22503633 - two cases from a single family with craniosynostosis, scaphocephaly and facial dysmorphy.
PMID:27874174 - single case with trigonocephaly and additional ciliopathy-related clinical features.
PMID:28288023 - single case with evolving craniofacial phenotype, striking brachydactyly and sensenbrenner syndromeand it was not clear if craniosynostosis was radiologically confirmed (as reviewed by Rebecca Tooze).
PMID:32007091 - single case with craniosynostosis and dolichocephaly.; Changed rating: GREEN; Changed publications to: 22503633, 27874174, 28288023, 32007091
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.71 IFT140 Achchuthan Shanmugasundram Phenotypes for gene: IFT140 were changed from hort-rib thoracic dysplasia 9 with or without polydactyly, OMIM:266920 to Short-rib thoracic dysplasia 9 with or without polydactyly, OMIM:266920
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.70 IFT140 Achchuthan Shanmugasundram Phenotypes for gene: IFT140 were changed from Short-rib thoracic dysplasia with or without polydactyly; asphyxiating thoracic dysplasia (ATD,Jeune) to hort-rib thoracic dysplasia 9 with or without polydactyly, OMIM:266920
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.69 IFT140 Achchuthan Shanmugasundram Publications for gene: IFT140 were set to
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.68 IFT140 Achchuthan Shanmugasundram Mode of inheritance for gene: IFT140 was changed from to BIALLELIC, autosomal or pseudoautosomal
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.67 IFT140 Achchuthan Shanmugasundram reviewed gene: IFT140: Rating: AMBER; Mode of pathogenicity: None; Publications: 27874174, 28288023, 32007091; Phenotypes: Short-rib thoracic dysplasia 9 with or without polydactyly, OMIM:266920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.67 GPC3 Achchuthan Shanmugasundram Classified gene: GPC3 as Amber List (moderate evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.67 GPC3 Achchuthan Shanmugasundram Added comment: Comment on list classification: The evidence is not sufficient for green rating and should be rated AMBER.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.67 GPC3 Achchuthan Shanmugasundram Gene: gpc3 has been classified as Amber List (Moderate Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.66 GPC3 Achchuthan Shanmugasundram Phenotypes for gene: GPC3 were changed from Simpson-Golabi-Behmel syndrome to Simpson-Golabi-Behmel syndrome, type 1, OMIM:312870
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.65 GPC3 Achchuthan Shanmugasundram Publications for gene: GPC3 were set to
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.64 GPC3 Achchuthan Shanmugasundram Mode of inheritance for gene: GPC3 was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.63 GPC3 Achchuthan Shanmugasundram commented on gene: GPC3: In addition to cases reviewed by Rebecca Tooze (University of Oxford), PMID:19372699 reported a prenatal case identified with hemizygous deletion in GPC3 gene (c.194-206del/ p.Cys65fs) and diagnosed with polyhydramnios, macrosomia, macroglossia, left-sided cleft lip and palate, nephromegaly, hepatosplenomegaly as well as an abnormal skull shape due to lamboid craniosynostosis via ultrasound at 30 weeks off gestation.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.63 GPC3 Achchuthan Shanmugasundram edited their review of gene: GPC3: Changed publications to: 19372699, 24115482, 25804025, 34429528
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.63 GPC3 Achchuthan Shanmugasundram reviewed gene: GPC3: Rating: AMBER; Mode of pathogenicity: None; Publications: 24115482, 25804025, 34429528; Phenotypes: Simpson-Golabi-Behmel syndrome, type 1, OMIM:312870; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.63 FREM1 Achchuthan Shanmugasundram Classified gene: FREM1 as Amber List (moderate evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.63 FREM1 Achchuthan Shanmugasundram Added comment: Comment on list classification: Although there are five cases with heterozygous variants in FREM1 gene associated with craniosynostosis/ trigonocephaly, there is also conflicting evidence suggesting there is no association of heterozygous variants in this gene with craniosynostosis. Hence, this gene can only be rated AMBER with the current evidence.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.63 FREM1 Achchuthan Shanmugasundram Gene: frem1 has been classified as Amber List (Moderate Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.62 FREM1 Achchuthan Shanmugasundram Phenotypes for gene: FREM1 were changed from Manitoba oculotrichoanal syndrome; bifid nose; trigonocephaly to Trigonocephaly 2, OMIM:614485
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.61 FREM1 Achchuthan Shanmugasundram Publications for gene: FREM1 were set to
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.60 FREM1 Achchuthan Shanmugasundram Mode of inheritance for gene: FREM1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.59 FREM1 Achchuthan Shanmugasundram reviewed gene: FREM1: Rating: ; Mode of pathogenicity: None; Publications: 21931569, 33038106, 33288889, 33937142; Phenotypes: Trigonocephaly 2, OMIM:614485; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v4.10 RHBDF2 Arina Puzriakova Publications for gene: RHBDF2 were set to
Primary immunodeficiency or monogenic inflammatory bowel disease v4.9 RHBDF2 Arina Puzriakova Classified gene: RHBDF2 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.9 RHBDF2 Arina Puzriakova Added comment: Comment on list classification: New gene added by Boaz Palterer. Not yet associated with an immune phenotype in OMIM or G2P, but note that monoallelic variants in this gene are associated with tylosis.

To date, 4 individuals from 2 unrelated families have been reported (PMID: 34937930) with LoF variants in this gene and recurrent infections. Functional data includes supportive mouse model.

Rating Amber for now awaiting at least one more corroborating case (added watchlist tag)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.9 RHBDF2 Arina Puzriakova Gene: rhbdf2 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v5.7 COASY Sarah Leigh Phenotypes for gene: COASY were changed from Severe prenatal onset pontocerebellar hypoplasia, microcephaly, arthrogryposis to Pontocerebellar hypoplasia, type 12, OMIM:618266; pontocerebellar hypoplasia, type 12, MONDO:0032643
Parkinson Disease and Complex Parkinsonism v1.113 COASY Sarah Leigh edited their review of gene: COASY: Added comment: Associated with Neurodegeneration with brain iron accumulation 6 (OMIM: 615643) and as definitive Gen2Phen gene for neurodegeneration with brain iron accumulation.
PMID: 24360804 & 28489334 report three COASY variants in three unrelated cases of OMIM: 615643. Supportive functional studies were also presented (PMID: 24360804). The neurological features of case II-2 of family 2, included Parkinsonian features (rigidity and abnormal postural reflexes). (PMID: 24360804).; Changed rating: AMBER
Primary immunodeficiency or monogenic inflammatory bowel disease v4.8 IKZF2 Arina Puzriakova Classified gene: IKZF2 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.8 IKZF2 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at then next GMS panel update. At least 6 unrelated families reported with variable features of immune dysregulation who harbour different deleterious heterozygous variants in the IKZF2 gene.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.8 IKZF2 Arina Puzriakova Gene: ikzf2 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.7 IKZF2 Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: IKZF2.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.7 IKZF2 Arina Puzriakova Publications for gene: IKZF2 were set to 34826260
Parkinson Disease and Complex Parkinsonism v1.113 COASY Sarah Leigh Deleted their comment
Parkinson Disease and Complex Parkinsonism v1.113 COASY Sarah Leigh Classified gene: COASY as Amber List (moderate evidence)
Parkinson Disease and Complex Parkinsonism v1.113 COASY Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Parkinson Disease and Complex Parkinsonism v1.113 COASY Sarah Leigh Gene: coasy has been classified as Amber List (Moderate Evidence).
Severe microcephaly v4.10 COASY Sarah Leigh Phenotypes for gene: COASY were changed from Pontocerebellar hypoplasia, type 12 OMIM:618266 to Pontocerebellar hypoplasia, type 12, OMIM:618266; pontocerebellar hypoplasia, type 12, MONDO:0032643
Parkinson Disease and Complex Parkinsonism v1.112 COASY Sarah Leigh Phenotypes for gene: COASY were changed from Neurodegeneration with brain iron accumulation 6, MIM# 615643 to Neurodegeneration with brain iron accumulation 6, OMIM:615643; neurodegeneration with brain iron accumulation 6, MONDO:0014290
Intellectual disability v5.118 COASY Sarah Leigh Phenotypes for gene: COASY were changed from Neurodegeneration with brain iron accumulation 6, 615643 to Neurodegeneration with brain iron accumulation 6, OMIM:615643; neurodegeneration with brain iron accumulation 6, MONDO:0014290
Mitochondrial disorders v4.35 COASY Sarah Leigh Phenotypes for gene: COASY were changed from Neurodegeneration with brain iron accumulation 6, 615643; Pontocerebellar hypoplasia, type 12, 618266 to Neurodegeneration with brain iron accumulation 6, OMIM:615643; neurodegeneration with brain iron accumulation 6, MONDO:0014290; Pontocerebellar hypoplasia, type 12, OMIM:618266; pontocerebellar hypoplasia, type 12, MONDO:0032643
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.59 DPH1 Achchuthan Shanmugasundram changed review comment from: Sagittal craniosynostosis was reported in one of the four North American patients identified with biallelic variants (c.17T>A/ p.Met6Lys) in DPH1 gene in PMID:26220823.

A family of two affected siblings identified with recessive variants (c.374 T > C/ p.Leu125Pro) in DPH1 presented with metopic synostosis.; to: Sagittal craniosynostosis was reported in one of the four North American patients identified with biallelic variants (c.17T>A/ p.Met6Lys) in DPH1 gene in PMID:26220823.

A family of two affected siblings identified with recessive variants (c.374 T > C/ p.Leu125Pro) in DPH1 presented with metopic synostosis.

This gene has been associated with relevant phenotypes in OMIM (MIM #616901).
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.59 DPH1 Achchuthan Shanmugasundram Phenotypes for gene: DPH1 were changed from to Developmental delay with short stature, dysmorphic facial features, and sparse hair, OMIM:616901
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.58 DPH1 Achchuthan Shanmugasundram Publications for gene: DPH1 were set to
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.57 DPH1 Achchuthan Shanmugasundram Classified gene: DPH1 as Amber List (moderate evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.57 DPH1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Rebecca Tooze (University of Oxford), there are only two unrelated cases. Hence, this gene should be rated AMBER.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.57 DPH1 Achchuthan Shanmugasundram Gene: dph1 has been classified as Amber List (Moderate Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.56 DPH1 Achchuthan Shanmugasundram reviewed gene: DPH1: Rating: AMBER; Mode of pathogenicity: None; Publications: 26220823, 30877278; Phenotypes: Developmental delay with short stature, dysmorphic facial features, and sparse hair, OMIM:616901; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v4.34 COASY Sarah Leigh Publications for gene: COASY were set to
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.56 DPF2 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Rebecca Tooze (University of Oxford), there are two cases of confirmed craniosynostosis with the same variant (p.Asp346Gly). Although there is a third case with trigonocephaly harbouring a different variant (p.Asp340Glufs*12), craniosynostosis was not radiologically confirmed in this individual. Hence, this gene should be rated AMBER.; to: Comment on list classification: As reviewed by Rebecca Tooze (University of Oxford), there are two cases of confirmed craniosynostosis with the same variant (p.Asp346Gly). Although there is a third case with trigonocephaly harbouring a different variant (p.Asp340Glufs*12), craniosynostosis was not radiologically confirmed in this individual. Hence, this gene should be rated AMBER.

This gene has been associated with Coffin-Siris syndrome in both OMIM (MIM #618027) and Gene2Phenotype (with a 'strong' rating in the DD panel).
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.56 DPF2 Achchuthan Shanmugasundram Publications for gene: DPF2 were set to
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.55 DPF2 Achchuthan Shanmugasundram Classified gene: DPF2 as Amber List (moderate evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.55 DPF2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Rebecca Tooze (University of Oxford), there are two cases of confirmed craniosynostosis with the same variant (p.Asp346Gly). Although there is a third case with trigonocephaly harbouring a different variant (p.Asp340Glufs*12), craniosynostosis was not radiologically confirmed in this individual. Hence, this gene should be rated AMBER.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.55 DPF2 Achchuthan Shanmugasundram Gene: dpf2 has been classified as Amber List (Moderate Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.54 DPF2 Achchuthan Shanmugasundram reviewed gene: DPF2: Rating: AMBER; Mode of pathogenicity: None; Publications: 29429572; Phenotypes: Coffin-Siris syndrome 7, OMIM:618027; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.54 ASXL3 Achchuthan Shanmugasundram Classified gene: ASXL3 as Amber List (moderate evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.54 ASXL3 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Rebecca Tooze (University of Oxford), there are only two cases of craniosynostosis and craniosynostosis was not confirmed in the third case. Hence, this gene should be rated AMBER.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.54 ASXL3 Achchuthan Shanmugasundram Gene: asxl3 has been classified as Amber List (Moderate Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.53 ASXL3 Achchuthan Shanmugasundram Phenotypes for gene: ASXL3 were changed from to Bainbridge-Ropers syndrome, OMIM:615485; craniosynostosis, MONDO:0015469
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.52 ASXL3 Achchuthan Shanmugasundram Publications for gene: ASXL3 were set to
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.51 ASXL3 Achchuthan Shanmugasundram reviewed gene: ASXL3: Rating: AMBER; Mode of pathogenicity: None; Publications: 24044690, 33288889; Phenotypes: Bainbridge-Ropers syndrome, OMIM:615485, craniosynostosis, MONDO:0015469; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Neurological ciliopathies v3.10 SUFU Arina Puzriakova Tag Q4_22_expert_review tag was added to gene: SUFU.
Ophthalmological ciliopathies v3.1 SUFU Arina Puzriakova Tag Q4_22_expert_review tag was added to gene: SUFU.
Intellectual disability v5.117 SUFU Arina Puzriakova Tag Q4_22_expert_review tag was added to gene: SUFU.
Ataxia and cerebellar anomalies - childhood onset v4.7 SUFU Arina Puzriakova Tag Q4_22_expert_review tag was added to gene: SUFU.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.51 SOX6 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: SOX6.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.51 SOX6 Achchuthan Shanmugasundram Phenotypes for gene: SOX6 were changed from craniosynostosis to Tolchin-Le Caignec syndrome, OMIM:618971; craniosynostosis
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.50 SOX6 Achchuthan Shanmugasundram Publications for gene: SOX6 were set to 32442410; 16258006
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.49 SOX6 Achchuthan Shanmugasundram Mode of inheritance for gene: SOX6 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.48 SOX6 Achchuthan Shanmugasundram Classified gene: SOX6 as Amber List (moderate evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.48 SOX6 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Rebecca Tooze (University of Oxford), there is sufficient evidence available (seven unrelated cases) for this gene to be promoted to GREEN rating in the next GMS update.

In addition, this gene has also been associated with relevant phenotypes in both OMIM (MIM #618971 ) and Gene2Phenotype (with 'strong' rating in the DD panel).
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.48 SOX6 Achchuthan Shanmugasundram Gene: sox6 has been classified as Amber List (Moderate Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.47 SOX6 Achchuthan Shanmugasundram reviewed gene: SOX6: Rating: GREEN; Mode of pathogenicity: None; Publications: 16258006, 32442410, 36118902, 36980886; Phenotypes: Tolchin-Le Caignec syndrome, OMIM:618971; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.47 PRRX1 Achchuthan Shanmugasundram Classified gene: PRRX1 as Amber List (moderate evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.47 PRRX1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Rebecca Tooze (University of Oxford) and reported in PMID:37154149, there is sufficient evidence for this gene to be promoted to GREEN at the next GMS update.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.47 PRRX1 Achchuthan Shanmugasundram Gene: prrx1 has been classified as Amber List (Moderate Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.46 PRRX1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: PRRX1.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.46 PRRX1 Achchuthan Shanmugasundram Phenotypes for gene: PRRX1 were changed from craniosynostosis, various combinations of sutures to Agnathia-otocephaly complex, OMIM:202650; craniosynostosis, MONDO:0015469; craniosynostosis, various combinations of sutures
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.45 PRRX1 Achchuthan Shanmugasundram Publications for gene: PRRX1 were set to
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.44 PRRX1 Achchuthan Shanmugasundram edited their review of gene: PRRX1: Added comment: PMID:37154149 reported 15 patients from 12 unrelated families presenting with craniosynostosis and were identified with heterozygous variants in PRRX1 gene, while three cases from three additional families had deletion (family 13: 61.5kb; family 14: 76kb; family 15: 10.5Mb deletion). These consisted of three de novo variants, but for the majority of cases the variant was inherited from an unaffected parent, yielding an estimate for the penetrance of craniosynostosis of 12.5%. These results were also supported by immunofluorescence analyses which showed that missense variants within the PRRX1 homeodomain cause abnormal nuclear localisation.; Changed phenotypes to: Agnathia-otocephaly complex, OMIM:202650, craniosynostosis, MONDO:0015469
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.44 PRRX1 Achchuthan Shanmugasundram reviewed gene: PRRX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 36980886, 37154149; Phenotypes: Agnathia-otocephaly complex, OMIM:202650; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.44 NFIX Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: NFIX.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.44 NFIX Achchuthan Shanmugasundram Classified gene: NFIX as Amber List (moderate evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.44 NFIX Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Rebecca Tooze (University of Oxford), there is sufficient evidence (4 unrelated cases) available for promotion of this gene to GREEN rating in the next GMS update.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.44 NFIX Achchuthan Shanmugasundram Gene: nfix has been classified as Amber List (Moderate Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.43 NFIX Achchuthan Shanmugasundram Phenotypes for gene: NFIX were changed from Marshall-Smith syndrome to Malan syndrome, OMIM:614753; Marshall-Smith syndrome, OMIM:602535; craniosynostosis, MONDO:0015469
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.42 NFIX Achchuthan Shanmugasundram edited their review of gene: NFIX: Changed phenotypes to: Malan syndrome, OMIM:614753, Marshall-Smith syndrome, OMIM:602535, craniosynostosis, MONDO:0015469
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.42 NFIX Achchuthan Shanmugasundram Publications for gene: NFIX were set to
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.41 NFIX Achchuthan Shanmugasundram Mode of inheritance for gene: NFIX was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.40 NFIX Achchuthan Shanmugasundram reviewed gene: NFIX: Rating: GREEN; Mode of pathogenicity: None; Publications: 33288889, 35997807; Phenotypes: Malan syndrome, OMIM:614753, Marshall-Smith syndrome, OMIM:602535; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.40 MAN2B1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: MAN2B1.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.40 MAN2B1 Achchuthan Shanmugasundram Classified gene: MAN2B1 as Amber List (moderate evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.40 MAN2B1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Rebecca Tooze (University of Oxford), there are three unrelated cases identified with biallelic variants in MAN2B1 gene presented with craniosynostosis, although there are several other cases identified with biallelic variants in MAN2B1, who did not present with craniosynostosis. As there are three unrelated cases with craniosynostosis, this gene can be promoted to GREEN rating in the next GMS update.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.40 MAN2B1 Achchuthan Shanmugasundram Gene: man2b1 has been classified as Amber List (Moderate Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.39 MAN2B1 Achchuthan Shanmugasundram Phenotypes for gene: MAN2B1 were changed from to Mannosidosis, alpha-, types I and II, OMIM:248500
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.38 MAN2B1 Achchuthan Shanmugasundram Publications for gene: MAN2B1 were set to
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.37 MAN2B1 Achchuthan Shanmugasundram reviewed gene: MAN2B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33288889, 34429528, 35242565; Phenotypes: Mannosidosis, alpha-, types I and II, OMIM:248500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.37 KAT6B Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: KAT6B.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.37 KAT6B Achchuthan Shanmugasundram Classified gene: KAT6B as Amber List (moderate evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.37 KAT6B Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Rebecca Tooze (University of Oxford), there are three unrelated cases to support the promotion of this gene to GREEN rating in the next GMS update.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.37 KAT6B Achchuthan Shanmugasundram Gene: kat6b has been classified as Amber List (Moderate Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.36 KAT6B Achchuthan Shanmugasundram Phenotypes for gene: KAT6B were changed from KAT6B-related disorders to KAT6B-related disorders; Genitopatellar syndrome, OMIM:606170
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.35 KAT6B Achchuthan Shanmugasundram Publications for gene: KAT6B were set to
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.34 KAT6B Achchuthan Shanmugasundram Mode of inheritance for gene: KAT6B was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.33 KAT6B Achchuthan Shanmugasundram reviewed gene: KAT6B: Rating: GREEN; Mode of pathogenicity: None; Publications: 28696035, 33288889; Phenotypes: Genitopatellar syndrome, OMIM:606170; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.33 IL6ST Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: IL6ST.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.33 IL6ST Achchuthan Shanmugasundram Classified gene: IL6ST as Amber List (moderate evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.33 IL6ST Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Rebecca Tooze (University of Oxford), there are two unrelated cases and supporting functional studies in mice. Hence, this gene can be promoted to GREEN at the next GMS update.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.33 IL6ST Achchuthan Shanmugasundram Gene: il6st has been classified as Amber List (Moderate Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.32 IL6ST Achchuthan Shanmugasundram Phenotypes for gene: IL6ST were changed from to Hyper-IgE recurrent infection syndrome 4B, autosomal recessive, OMIM:618523
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.31 IL6ST Achchuthan Shanmugasundram Publications for gene: IL6ST were set to
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.30 IL6ST Achchuthan Shanmugasundram reviewed gene: IL6ST: Rating: GREEN; Mode of pathogenicity: None; Publications: 28747427, 32566365; Phenotypes: Hyper-IgE recurrent infection syndrome 4B, autosomal recessive, OMIM:618523; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.30 FGF9 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: FGF9.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.30 FGF9 Achchuthan Shanmugasundram Classified gene: FGF9 as Amber List (moderate evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.30 FGF9 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Rebecca Tooze (University of Oxford), there are two unrelated cases and supporting functional evidence available for this gene. Hence, it can be promoted to GREEN at the next GMS update.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.30 FGF9 Achchuthan Shanmugasundram Gene: fgf9 has been classified as Amber List (Moderate Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.29 FGF9 Achchuthan Shanmugasundram Phenotypes for gene: FGF9 were changed from to Multiple synostoses syndrome 3, OMIM:612961
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.28 FGF9 Achchuthan Shanmugasundram Publications for gene: FGF9 were set to
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.27 FGF9 Achchuthan Shanmugasundram Mode of inheritance for gene: FGF9 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.26 FGF9 Achchuthan Shanmugasundram reviewed gene: FGF9: Rating: GREEN; Mode of pathogenicity: None; Publications: 12140681, 19589401, 28730625; Phenotypes: Multiple synostoses syndrome 3, OMIM:612961; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.26 FBXO11 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: FBXO11.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.26 FBXO11 Achchuthan Shanmugasundram Classified gene: FBXO11 as Amber List (moderate evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.26 FBXO11 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Rebecca Tooze (University of Oxford), there are three unrelated cases reported with variants in this gene and craniosynostosis. Hence, this gene can be promoted to GREEN at the next GMS update.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.26 FBXO11 Achchuthan Shanmugasundram Gene: fbxo11 has been classified as Amber List (Moderate Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.25 FBXO11 Achchuthan Shanmugasundram Phenotypes for gene: FBXO11 were changed from to Intellectual developmental disorder with dysmorphic facies and behavioral abnormalities, OMIM:618089
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.24 FBXO11 Achchuthan Shanmugasundram Publications for gene: FBXO11 were set to
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.23 FBXO11 Achchuthan Shanmugasundram reviewed gene: FBXO11: Rating: GREEN; Mode of pathogenicity: None; Publications: 30057029, 34429528; Phenotypes: Intellectual developmental disorder with dysmorphic facies and behavioral abnormalities, OMIM:618089; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.117 RNF13 Arina Puzriakova Phenotypes for gene: RNF13 were changed from Cortical visual impairment; Epileptic encephalopathy, early infantile, 73, 618379; Failure to thrive; Seizures; Congenital microcephaly; Abnormal muscle tone; Feeding difficulties; Intellectual disability; Global developmental delay; Sensorineural hearing impairment to Developmental and epileptic encephalopathy 73, OMIM:618379
Early onset or syndromic epilepsy v4.36 RNF13 Arina Puzriakova Phenotypes for gene: RNF13 were changed from Cortical visual impairment; Failure to thrive; Seizures; Congenital microcephaly; Epileptic encephalopathy, early infantile, 73; Abnormal muscle tone; Feeding difficulties; Intellectual disability; Global developmental delay; Sensorineural hearing impairment to Developmental and epileptic encephalopathy 73, OMIM:618379
Intellectual disability v5.116 CHMP3 Arina Puzriakova Classified gene: CHMP3 as Red List (low evidence)
Intellectual disability v5.116 CHMP3 Arina Puzriakova Added comment: Comment on list classification: Rating Red for now as only a single case has been reported to date.
Intellectual disability v5.116 CHMP3 Arina Puzriakova Gene: chmp3 has been classified as Red List (Low Evidence).
Early onset or syndromic epilepsy v4.35 CHMP3 Arina Puzriakova Classified gene: CHMP3 as Red List (low evidence)
Early onset or syndromic epilepsy v4.35 CHMP3 Arina Puzriakova Added comment: Comment on list classification: Rating Red for now as only a single case has been reported to date.
Early onset or syndromic epilepsy v4.35 CHMP3 Arina Puzriakova Gene: chmp3 has been classified as Red List (Low Evidence).
Hereditary spastic paraplegia, childhood onset v4.8 CHMP3 Arina Puzriakova Classified gene: CHMP3 as Red List (low evidence)
Hereditary spastic paraplegia, childhood onset v4.8 CHMP3 Arina Puzriakova Added comment: Comment on list classification: Rating Red for now as only a single case has been reported to date.
Hereditary spastic paraplegia, childhood onset v4.8 CHMP3 Arina Puzriakova Gene: chmp3 has been classified as Red List (Low Evidence).
Early onset or syndromic epilepsy v4.34 CHMP3 Arina Puzriakova gene: CHMP3 was added
gene: CHMP3 was added to Early onset or syndromic epilepsy. Sources: Literature
Mode of inheritance for gene: CHMP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHMP3 were set to 35710109
Phenotypes for gene: CHMP3 were set to Complex spastic quadriplegia associated with developmental delay and seizures
Added comment: Cohen-Barak et al., 2022 (PMID: 35710109) reported on a consanguineous family, in which five individuals presented with intellectual and progressive motor disabilities, seizures and spastic quadriplegia, associated with a homozygous variant in CHMP3. Patient derived fibroblasts expressed ultrastructural and molecular features of impaired autophagy, partially rescued by ectopic expression of WT-CHMP3.
Sources: Literature
Intellectual disability v5.115 CHMP3 Arina Puzriakova gene: CHMP3 was added
gene: CHMP3 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: CHMP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHMP3 were set to 35710109
Phenotypes for gene: CHMP3 were set to Complex spastic quadriplegia associated with developmental delay and seizures
Added comment: Cohen-Barak et al., 2022 (PMID: 35710109) reported on a consanguineous family, in which five individuals presented with intellectual and progressive motor disabilities, seizures and spastic quadriplegia, associated with a homozygous variant in CHMP3. Patient derived fibroblasts expressed ultrastructural and molecular features of impaired autophagy, partially rescued by ectopic expression of WT-CHMP3.
Sources: Literature
Hereditary spastic paraplegia, childhood onset v4.7 CHMP3 Arina Puzriakova gene: CHMP3 was added
gene: CHMP3 was added to Childhood onset hereditary spastic paraplegia. Sources: Literature
Mode of inheritance for gene: CHMP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHMP3 were set to 35710109
Phenotypes for gene: CHMP3 were set to Complex spastic quadriplegia associated with developmental delay and seizures
Added comment: Cohen-Barak et al., 2022 (PMID: 35710109) reported on a consanguineous family, in which five individuals presented with intellectual and progressive motor disabilities, seizures and spastic quadriplegia, associated with a homozygous variant in CHMP3. Patient derived fibroblasts expressed ultrastructural and molecular features of impaired autophagy, partially rescued by ectopic expression of WT-CHMP3.
Sources: Literature
Early onset or syndromic epilepsy v4.33 RAC3 Arina Puzriakova Classified gene: RAC3 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.33 RAC3 Arina Puzriakova Added comment: Comment on list classification: There are now at least 14 patients from 13 unrelated families with de novo heterozygous variants in this gene (PMIDs: 29276006; 30293988; 35851598; 35595279). Seizures reported in at least 8 individuals. Therefore, this gene can be promoted to Green at the next GMS panel update.
Early onset or syndromic epilepsy v4.33 RAC3 Arina Puzriakova Gene: rac3 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v4.3 RAC3 Arina Puzriakova changed review comment from: Comment on list classification: There are now at least 14 patients from 13 unrelated families with de novo heterozygous variants in this gene (PMIDs: 29276006; 30293988; 35851598; 35595279). Brain imaging has shown variable structural abnormalities in all patients, including cerebral dysgenesis with polymicrogyria and heterotopia in the majority.; to: Comment on list classification: There are now at least 14 patients from 13 unrelated families with de novo heterozygous variants in this gene (PMIDs: 29276006; 30293988; 35851598; 35595279). Brain imaging has shown variable structural abnormalities in all patients, including cerebral dysgenesis with polymicrogyria and heterotopia in the majority. Therefore, this gene can be promoted to Green at the next GMS panel update.
Malformations of cortical development v4.3 RAC3 Arina Puzriakova Classified gene: RAC3 as Amber List (moderate evidence)
Malformations of cortical development v4.3 RAC3 Arina Puzriakova Added comment: Comment on list classification: There are now at least 14 patients from 13 unrelated families with de novo heterozygous variants in this gene (PMIDs: 29276006; 30293988; 35851598; 35595279). Brain imaging has shown variable structural abnormalities in all patients, including cerebral dysgenesis with polymicrogyria and heterotopia in the majority.
Malformations of cortical development v4.3 RAC3 Arina Puzriakova Gene: rac3 has been classified as Amber List (Moderate Evidence).
Dilated and arrhythmogenic cardiomyopathy v2.10 RRAGC Arina Puzriakova Tag Q2_23_NHS_review was removed from gene: RRAGC.
Dilated and arrhythmogenic cardiomyopathy v2.10 RRAGC Arina Puzriakova Entity copied from Paediatric or syndromic cardiomyopathy v3.12
Dilated and arrhythmogenic cardiomyopathy v2.10 RRAGC Arina Puzriakova gene: RRAGC was added
gene: RRAGC was added to Dilated and arrhythmogenic cardiomyopathy. Sources: NHS GMS,Literature,Expert Review Amber
Q2_23_promote_green, Q2_23_NHS_review tags were added to gene: RRAGC.
Mode of inheritance for gene: RRAGC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RRAGC were set to 27234373; 37057673
Phenotypes for gene: RRAGC were set to Dilated cardiomyopathy, hepatopathy and brain abnormalities
Penetrance for gene: RRAGC were set to unknown
Paediatric or syndromic cardiomyopathy v3.12 RRAGC Arina Puzriakova Classified gene: RRAGC as Amber List (moderate evidence)
Paediatric or syndromic cardiomyopathy v3.12 RRAGC Arina Puzriakova Added comment: Comment on list classification: New gene added by Hannah Robinson (South West Genomic Laboratory Hub). Sufficient evidence to promote this gene to Green at the next GMS panel update.
Paediatric or syndromic cardiomyopathy v3.12 RRAGC Arina Puzriakova Gene: rragc has been classified as Amber List (Moderate Evidence).
Paediatric or syndromic cardiomyopathy v3.11 RRAGC Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: RRAGC.
Tag Q2_23_NHS_review tag was added to gene: RRAGC.
Paediatric or syndromic cardiomyopathy v3.11 RRAGC Arina Puzriakova Phenotypes for gene: RRAGC were changed from to Dilated cardiomyopathy, hepatopathy and brain abnormalities
Paediatric or syndromic cardiomyopathy v3.10 RRAGC Arina Puzriakova Publications for gene: RRAGC were set to 27234373
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.23 FBN1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: FBN1.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.23 FBN1 Achchuthan Shanmugasundram Classified gene: FBN1 as Amber List (moderate evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.23 FBN1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Rebecca Tooze (University of Oxford), there is sufficient evidence (>3 unrelated cases) for this gene to be promoted to GREEN in the next GMS update.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.23 FBN1 Achchuthan Shanmugasundram Gene: fbn1 has been classified as Amber List (Moderate Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.22 FBN1 Achchuthan Shanmugasundram Phenotypes for gene: FBN1 were changed from Marfan syndrome to Marfan syndrome, OMIM:154700; Marfan lipodystrophy syndrome, OMIM:616914; craniosynostosis, MONDO:0015469
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.21 FBN1 Achchuthan Shanmugasundram Publications for gene: FBN1 were set to
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.20 FBN1 Achchuthan Shanmugasundram Mode of inheritance for gene: FBN1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.19 FBN1 Achchuthan Shanmugasundram changed review comment from: PMID:16596670 reported two cases that had heterozygous FBN1 variants. One had scaphocephaly with indistinct coronal sutures and partial sagittal synostosis. Second had plagiocephaly with patent coronal, lambdoid and sagittal sutures. A third case had FBN1 deletion with dolichocephaly.

PMID:24039054 reported a girl with severe congenital lipodystrophy and a neonatal progeroid appearance. She exhibited an accelerated growth in height with a discrepant poor weight gain and a characteristic facial appearance with craniosynostosis. She was identified with the variant c.8175_8182del8bp/ p.Arg2726Glufs*9 in FBN1 gene.

PMID:27884935 reported the identification of a de novo splice variant in FBN1gene (c.8226+5G>A) in a patient with craniosynostosis.

PMID:29168297 reported two probands with variants in FBN1 (proband 1: c.1169C>T/ p.(Ser390Phe) & c.8149G>A/ p.(Glu2717Lys); proband 2: c.7661G>A/ p.(Arg2554Gln)) presenting with me topic (proband 1) and sagittal (proband 2) craniosynostosis.

PMID:31754721 reported a patient with Marfan syndrome identified with c.4096G>A/ p.(Glu1366Lys) variant in FBN1 gene. This patient presented with sagittal and bilambdoidal craniosynostosis.; to: PMID:16596670 reported two cases that had heterozygous FBN1 variants. One had scaphocephaly with indistinct coronal sutures and partial sagittal synostosis. Second had plagiocephaly with patent coronal, lambdoid and sagittal sutures. A third case had FBN1 deletion with dolichocephaly.

PMID:24039054 reported a girl with severe congenital lipodystrophy and a neonatal progeroid appearance. She exhibited an accelerated growth in height with a discrepant poor weight gain and a characteristic facial appearance with craniosynostosis. She was identified with the variant c.8175_8182del8bp/ p.Arg2726Glufs*9 in FBN1 gene.

PMID:27884935 reported the identification of a de novo splice variant in FBN1gene (c.8226+5G>A) in a patient with craniosynostosis.

PMID:29168297 reported two probands with variants in FBN1 (proband 1: c.1169C>T/ p.(Ser390Phe) & c.8149G>A/ p.(Glu2717Lys); proband 2: c.7661G>A/ p.(Arg2554Gln)) presenting with me topic (proband 1) and sagittal (proband 2) craniosynostosis.

PMID:31754721 reported a patient with Marfan syndrome identified with c.4096G>A/ p.(Glu1366Lys) variant in FBN1 gene. This patient presented with sagittal and bilambdoidal craniosynostosis.

This gene has been associated with relevant phenotypes in both OMIM and Gene2Phenotype databases.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.19 FBN1 Achchuthan Shanmugasundram edited their review of gene: FBN1: Changed phenotypes to: Marfan syndrome, OMIM:154700, Marfan lipodystrophy syndrome, OMIM:616914, craniosynostosis, MONDO:0015469
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.19 FBN1 Achchuthan Shanmugasundram reviewed gene: FBN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 16596670, 24039054, 27884935, 29168297, 31754721; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia, adult onset v4.9 RFC1 Joseph Shaw reviewed gene: RFC1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 35883251, 36250766, 36289003, 36524104, 36478048; Phenotypes: Ataxia, Neuropathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Malformations of cortical development v4.2 RAC3 Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: RAC3.
Early onset or syndromic epilepsy v4.32 RAC3 Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: RAC3.
Malformations of cortical development v4.2 RAC3 Arina Puzriakova Entity copied from Intellectual disability - microarray and sequencing v5.114
Malformations of cortical development v4.2 RAC3 Arina Puzriakova gene: RAC3 was added
gene: RAC3 was added to Malformations of cortical development. Sources: Literature,Expert Review Green
Mode of inheritance for gene: RAC3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RAC3 were set to 29276006; 30293988; 35851598; 35595279
Phenotypes for gene: RAC3 were set to Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies, OMIM:618577
Penetrance for gene: RAC3 were set to unknown
Mode of pathogenicity for gene: RAC3 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Early onset or syndromic epilepsy v4.32 RAC3 Arina Puzriakova Entity copied from Intellectual disability - microarray and sequencing v5.114
Early onset or syndromic epilepsy v4.32 RAC3 Arina Puzriakova gene: RAC3 was added
gene: RAC3 was added to Early onset or syndromic epilepsy. Sources: Literature,Expert Review Green
Mode of inheritance for gene: RAC3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RAC3 were set to 29276006; 30293988; 35851598; 35595279
Phenotypes for gene: RAC3 were set to Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies, OMIM:618577
Penetrance for gene: RAC3 were set to unknown
Mode of pathogenicity for gene: RAC3 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability v5.114 RAC3 Arina Puzriakova Publications for gene: RAC3 were set to 29276006; 30293988
Intellectual disability v5.113 RAC3 Arina Puzriakova Classified gene: RAC3 as Green List (high evidence)
Intellectual disability v5.113 RAC3 Arina Puzriakova Gene: rac3 has been classified as Green List (High Evidence).
Intellectual disability v5.112 RAC3 Arina Puzriakova All sources for gene: RAC3 were removed
Intellectual disability v5.112 RAC3 Arina Puzriakova All sources for gene: RAC3 were removed
Early onset or syndromic epilepsy v4.31 GLRA2 Arina Puzriakova Phenotypes for gene: GLRA2 were changed from Global developmental delay; Intellectual disability; Autism; Behavioral abnormality; Seizures; Microcephaly; Abnormality of eye movement to Intellectual developmental disorder, X-linked syndromic, Pilorge type, OMIM:301076
Intellectual disability v5.111 GRIN2B Arina Puzriakova Publications for gene: GRIN2B were set to
Early onset or syndromic epilepsy v4.30 GRIN2B Arina Puzriakova Publications for gene: GRIN2B were set to Endele et al (2010) Nature Genet 42(11): 1021-1028
Fetal anomalies v3.82 GRIN2B Arina Puzriakova Publications for gene: GRIN2B were set to
Intellectual disability v5.110 GRIN2B Arina Puzriakova Phenotypes for gene: GRIN2B were changed from Mental Retardation, Dominant; Mental retardation, autosomal dominant 6, 613970; AUTISM to Intellectual developmental disorder, autosomal dominant 6, with or without seizures, OMIM:613970; Developmental and epileptic encephalopathy 27, OMIM:616139
Fetal anomalies v3.81 GRIN2B Arina Puzriakova Phenotypes for gene: GRIN2B were changed from AUTISM; EPILEPTIC ENCEPHALOPATHY; MENTAL RETARDATION, AUTOSOMAL DOMINANT 6 to Intellectual developmental disorder, autosomal dominant 6, with or without seizures, OMIM:613970; Developmental and epileptic encephalopathy 27, OMIM:616139
Early onset or syndromic epilepsy v4.29 GRIN2B Arina Puzriakova Phenotypes for gene: GRIN2B were changed from Mental retardation, autosomal dominant 6; Epileptic encephalopathy, early infantile, 27; EPILEPTIC ENCEPHALOPATHY; AUTISM to Intellectual developmental disorder, autosomal dominant 6, with or without seizures, OMIM:613970; Developmental and epileptic encephalopathy 27, OMIM:616139
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.19 BCL11B Achchuthan Shanmugasundram Tag Q2_21_NHS_review was removed from gene: BCL11B.
Tag Q2_23_NHS_review tag was added to gene: BCL11B.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.19 CDK13 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: CDK13.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.19 CDK13 Achchuthan Shanmugasundram Classified gene: CDK13 as Amber List (moderate evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.19 CDK13 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Rebecca Tooze (University of Oxford), there are four unrelated cases identified with heterozygous variants in CDK13 gene and presenting with craniosynostosis. Hence, this gene can be promoted to GREEN at the next GMS update.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.19 CDK13 Achchuthan Shanmugasundram Gene: cdk13 has been classified as Amber List (Moderate Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.18 CDK13 Achchuthan Shanmugasundram Publications for gene: CDK13 were set to
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.17 CDK13 Achchuthan Shanmugasundram Phenotypes for gene: CDK13 were changed from to Congenital heart defects, dysmorphic facial features, and intellectual developmental disorder, OMIM:617360; craniosynostosis, MONDO:0015469
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.16 CDK13 Achchuthan Shanmugasundram reviewed gene: CDK13: Rating: GREEN; Mode of pathogenicity: None; Publications: 28807008, 33288889, 34429528; Phenotypes: Congenital heart defects, dysmorphic facial features, and intellectual developmental disorder, OMIM:617360, craniosynostosis, MONDO:0015469; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v3.80 SCUBE3 Arina Puzriakova Classified gene: SCUBE3 as Amber List (moderate evidence)
Fetal anomalies v3.80 SCUBE3 Arina Puzriakova Added comment: Comment on list classification: Confirmed with Stephanie Allen that the GMS Fetal expert group determined there is sufficient evidence to classify this gene as Green (9th May 2023).
Fetal anomalies v3.80 SCUBE3 Arina Puzriakova Gene: scube3 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v3.79 SCUBE3 Arina Puzriakova Tag to_be_confirmed_NHSE was removed from gene: SCUBE3.
Tag Q3_22_rating was removed from gene: SCUBE3.
Tag Q3_22_expert_review was removed from gene: SCUBE3.
Fetal anomalies v3.79 RAB11A Arina Puzriakova Classified gene: RAB11A as Amber List (moderate evidence)
Fetal anomalies v3.79 RAB11A Arina Puzriakova Added comment: Comment on list classification: Confirmed with Stephanie Allen that the GMS Fetal expert group determined there is sufficient evidence to classify this gene as Green (9th May 2023).
Fetal anomalies v3.79 RAB11A Arina Puzriakova Gene: rab11a has been classified as Amber List (Moderate Evidence).
Fetal anomalies v3.78 RAB11A Arina Puzriakova Tag to_be_confirmed_NHSE was removed from gene: RAB11A.
Tag Q3_22_rating was removed from gene: RAB11A.
Tag Q3_22_expert_review was removed from gene: RAB11A.
Fetal anomalies v3.78 MRPS14 Arina Puzriakova commented on gene: MRPS14
Fetal anomalies v3.78 GATB Arina Puzriakova changed review comment from: Confirmed with Stephanie Allen that there is sufficient evidence to classify this gene as Green. Additional comments: "One family with two affected compound heterozygotes reported; however, GATB, GATC & QRSL1 function together and this is supported by functional work, therefore classified as green when combining cases across the 3 genes."; to: Confirmed with Stephanie Allen that there is sufficient evidence to classify this gene as Green (9th May 2023). Additional comments: "One family with two affected compound heterozygotes reported; however, GATB, GATC & QRSL1 function together and this is supported by functional work, therefore classified as green when combining cases across the 3 genes."
Fetal anomalies v3.78 MRPS14 Arina Puzriakova Tag to_be_confirmed_NHSE was removed from gene: MRPS14.
Tag Q2_23_promote_green was removed from gene: MRPS14.
Tag Q2_23_NHS_review was removed from gene: MRPS14.
Fetal anomalies v3.78 GATB Arina Puzriakova commented on gene: GATB
Fetal anomalies v3.78 GATB Arina Puzriakova Tag to_be_confirmed_NHSE was removed from gene: GATB.
Skeletal dysplasia v4.2 PKDCC Eleanor Williams Classified gene: PKDCC as Green List (high evidence)
Skeletal dysplasia v4.2 PKDCC Eleanor Williams Added comment: Comment on list classification: Further expert review from Alistair Pagnamenta supports the green rating of this gene. No change in rating needed as is green already.
Skeletal dysplasia v4.2 PKDCC Eleanor Williams Gene: pkdcc has been classified as Green List (High Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.16 BCL11B Eleanor Williams Tag Q2_21_NHS_review tag was added to gene: BCL11B.
Monogenic hearing loss v4.9 ATP2B2 Eleanor Williams Classified gene: ATP2B2 as Amber List (moderate evidence)
Monogenic hearing loss v4.9 ATP2B2 Eleanor Williams Added comment: Comment on list classification: There is now enough evidence to show that variants in this gene can cause hearing loss so the recommendation is that this gene is rated Green following GMS review.
Monogenic hearing loss v4.9 ATP2B2 Eleanor Williams Gene: atp2b2 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v4.8 ATP2B2 Eleanor Williams Phenotypes for gene: ATP2B2 were changed from {Deafness, autosomal recessive 12, modifier of} 601386 to {Deafness, autosomal recessive 12, modifier of}, OMIM:601386; Deafness, autosomal dominant 82, OMIM:619804; hearing loss, autosomal dominant 82, MONDO:0030719
Monogenic hearing loss v4.7 ATP2B2 Eleanor Williams Publications for gene: ATP2B2 were set to 30535804; 17234811
Monogenic hearing loss v4.6 ATP2B2 Eleanor Williams Tag Q2_23_promote_green tag was added to gene: ATP2B2.
Tag Q2_23_NHS_review tag was added to gene: ATP2B2.
Monogenic hearing loss v4.6 ATP2B2 Eleanor Williams changed review comment from: Comment on list classification: Promoting from red to amber. PMID 30535804 reports 5 independent cases of autosomal dominant hearing impairment in individuals with truncating or splice site variants. Rare variants in CDH23 were considered unlikely to be causative. However, they cannot exclude a modifying effect of the CDH23 variants on HI, therefore rating amber until further cases on monogenic hearing loss with ATP2B2 are reported.; to: Comment on list classification: Promoting from red to amber. PMID 30535804 reports 5 independent cases of autosomal dominant hearing impairment in individuals with truncating or splice site variants. Rare variants in CDH23 were considered unlikely to be causative. However, they cannot exclude a modifying effect of the CDH23 variants on Hearing impairment, therefore rating amber until further cases on monogenic hearing loss with ATP2B2 are reported.
Paediatric disorders - additional genes v3.2 WNT9B Arina Puzriakova Entity copied from Fetal anomalies v3.78
Paediatric disorders - additional genes v3.2 WNT9B Arina Puzriakova gene: WNT9B was added
gene: WNT9B was added to Paediatric disorders - additional genes. Sources: Literature,Expert Review Amber
watchlist tags were added to gene: WNT9B.
Mode of inheritance for gene: WNT9B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WNT9B were set to 34145744
Phenotypes for gene: WNT9B were set to Renal agenesis/hypoplasia/dysplasia
Fetal anomalies v3.78 WNT9B Arina Puzriakova Classified gene: WNT9B as Amber List (moderate evidence)
Fetal anomalies v3.78 WNT9B Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). Not yet associated with any phenotype in OMIM or G2P. Rating Amber as to date, only two cases have been reported in one paper but with a watchlist tag to monitor for additional cases.
Fetal anomalies v3.78 WNT9B Arina Puzriakova Gene: wnt9b has been classified as Amber List (Moderate Evidence).
Fetal anomalies v3.77 WNT9B Arina Puzriakova Tag watchlist tag was added to gene: WNT9B.
Mitochondrial disorders v4.33 LETM1 Sarah Leigh Tag Q2_23_promote_green tag was added to gene: LETM1.
Likely inborn error of metabolism v4.34 LETM1 Sarah Leigh Tag Q2_23_promote_green tag was added to gene: LETM1.
Mitochondrial disorders v4.33 LETM1 Sarah Leigh Mode of inheritance for gene: LETM1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v4.34 LETM1 Sarah Leigh Mode of inheritance for gene: LETM1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v4.33 LETM1 Sarah Leigh Phenotypes for gene: LETM1 were changed from Multiple respiratory chain complex deficiencies (disorders of protein synthesis) to Neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction, OMIM:620089
Mitochondrial disorders v4.32 LETM1 Sarah Leigh Phenotypes for gene: LETM1 were changed from Multiple respiratory chain complex deficiencies (disorders of protein synthesis) to Neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction, OMIM:620089
Likely inborn error of metabolism v4.32 LETM1 Sarah Leigh Publications for gene: LETM1 were set to
Mitochondrial disorders v4.31 LETM1 Sarah Leigh Publications for gene: LETM1 were set to
Severe microcephaly v4.9 WLS Arina Puzriakova changed review comment from: Comment on list classification: There are sufficient unrelated cases with different homozygous variants in this gene and a consistent phenotype to support a gene-disease association. Some features such as microcephaly and digit malformations may plausibly be detected prenatally and therefore suggesting this gene is rated Green at the next GMS panel update.; to: Comment on list classification: There are sufficient unrelated cases with different homozygous variants in this gene and a consistent phenotype to support a gene-disease association. Progressive microcephaly (head circumference, 2 to 5.9 SD below the mean) was seen in all affected patients for whom data were available. Therefore suggesting this gene is rated Green at the next GMS panel update.
Severe microcephaly v4.9 WLS Arina Puzriakova Entity copied from Fetal anomalies v3.77
Severe microcephaly v4.9 WLS Arina Puzriakova gene: WLS was added
gene: WLS was added to Severe microcephaly. Sources: Literature,Expert Review Amber
Q2_23_promote_green tags were added to gene: WLS.
Mode of inheritance for gene: WLS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WLS were set to 34587386
Phenotypes for gene: WLS were set to Zaki syndrome, OMIM:619648
Fetal anomalies v3.77 WLS Arina Puzriakova Classified gene: WLS as Amber List (moderate evidence)
Fetal anomalies v3.77 WLS Arina Puzriakova Added comment: Comment on list classification: There are sufficient unrelated cases with different homozygous variants in this gene and a consistent phenotype to support a gene-disease association. Some features such as microcephaly and digit malformations may plausibly be detected prenatally and therefore suggesting this gene is rated Green at the next GMS panel update.
Fetal anomalies v3.77 WLS Arina Puzriakova Gene: wls has been classified as Amber List (Moderate Evidence).
Fetal anomalies v3.76 WLS Arina Puzriakova Phenotypes for gene: WLS were changed from structural congenital anomalies to Zaki syndrome, OMIM:619648
Fetal anomalies v3.75 WLS Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: WLS.
Intellectual disability v5.109 LHX2 Sarah Leigh Classified gene: LHX2 as Amber List (moderate evidence)
Intellectual disability v5.109 LHX2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Intellectual disability v5.109 LHX2 Sarah Leigh Gene: lhx2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.108 LHX2 Sarah Leigh gene: LHX2 was added
gene: LHX2 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Q2_23_promote_green tags were added to gene: LHX2.
Mode of inheritance for gene: LHX2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: LHX2 were set to 37057675
Phenotypes for gene: LHX2 were set to neurodevelopmental disorder
Review for gene: LHX2 was set to GREEN
Added comment: Not associated with a phenotype in OMIM, Gen2Phen or MONDO. PMID: 37057675 reports 17 predominanly de novo LHX2 variants in a panel of patients with a variable neurodevelopmental disorder. Haploinsufficiency and functional studies are supportive of a loss-of-function pathogenic action of the reported LHX2 variants.
Sources: Literature
Paediatric pseudo-obstruction syndrome v1.3 MYL9 Arina Puzriakova Classified gene: MYL9 as Amber List (moderate evidence)
Paediatric pseudo-obstruction syndrome v1.3 MYL9 Arina Puzriakova Added comment: Comment on list classification: There is now sufficient evidence to rate this gene as Green at the next GMS panel update.
Paediatric pseudo-obstruction syndrome v1.3 MYL9 Arina Puzriakova Gene: myl9 has been classified as Amber List (Moderate Evidence).
Paediatric pseudo-obstruction syndrome v1.2 MYL9 Arina Puzriakova reviewed gene: MYL9: Rating: ; Mode of pathogenicity: None; Publications: 29453416, 33031641, 32621347, 33264186; Phenotypes: Megacystis-microcolon-intestinal hypoperistalsis syndrome 4, OMIM:619365; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.75 MYL9 Arina Puzriakova Classified gene: MYL9 as Amber List (moderate evidence)
Fetal anomalies v3.75 MYL9 Arina Puzriakova Added comment: Comment on list classification: There is now sufficient evidence to rate this gene as Green at the next GMS panel update.
Fetal anomalies v3.75 MYL9 Arina Puzriakova Gene: myl9 has been classified as Amber List (Moderate Evidence).
Paediatric pseudo-obstruction syndrome v1.2 MYL9 Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: MYL9.
Paediatric pseudo-obstruction syndrome v1.2 MYL9 Arina Puzriakova Publications for gene: MYL9 were set to 27481187; 31848803; 33031641; 33729000
Fetal anomalies v3.74 MYL9 Arina Puzriakova Publications for gene: MYL9 were set to 29453416; 33031641
Fetal anomalies v3.73 MYL9 Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: MYL9.
Fetal anomalies v3.73 MYL9 Arina Puzriakova commented on gene: MYL9: Third family reported by Billon et al. 2020 (PMID: 32621347) with the same homozygous exon 4 deletion of MYL9 as the one detected by Moreno et al. 2018 (PMID: 29453416) in an unrelated case. Family includes three sibs affected with megacystis, intestinal malrotation, small and thin colon, as well as some dysmorphic features. Fetopathological examination confirmed the diagnosis of MMIHS.
Mitochondrial disorders v4.30 OGDH Sarah Leigh Classified gene: OGDH as Amber List (moderate evidence)
Mitochondrial disorders v4.30 OGDH Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Mitochondrial disorders v4.30 OGDH Sarah Leigh Gene: ogdh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v4.31 OGDH Sarah Leigh Classified gene: OGDH as Amber List (moderate evidence)
Likely inborn error of metabolism v4.31 OGDH Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Likely inborn error of metabolism v4.31 OGDH Sarah Leigh Gene: ogdh has been classified as Amber List (Moderate Evidence).
Undiagnosed metabolic disorders v1.587 OGDH Sarah Leigh Classified gene: OGDH as Green List (high evidence)
Undiagnosed metabolic disorders v1.587 OGDH Sarah Leigh Gene: ogdh has been classified as Green List (High Evidence).
Likely inborn error of metabolism v4.30 OGDH Sarah Leigh Tag Q2_23_promote_green tag was added to gene: OGDH.
Mitochondrial disorders v4.29 OGDH Sarah Leigh Tag Q2_23_promote_green tag was added to gene: OGDH.
Mitochondrial disorders v4.29 OGDH Sarah Leigh edited their review of gene: OGDH: Added comment: Associated with relevant phenotype in OMIM and as moderate Gen2Phen gene. At least four variants have been reported in four unrelated cases, together with supportive functional studies (PMIDs: 32383294, 36520152).; Changed rating: GREEN
Undiagnosed metabolic disorders v1.586 OGDH Sarah Leigh reviewed gene: OGDH: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Likely inborn error of metabolism v4.30 OGDH Sarah Leigh reviewed gene: OGDH: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Likely inborn error of metabolism v4.30 OGDH Sarah Leigh Mode of inheritance for gene: OGDH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v4.29 OGDH Sarah Leigh Phenotypes for gene: OGDH were changed from Alpha-ketoglutarate dehydrogenase deficiency, OMIM:203740; oxoglutaricaciduria, MONDO:0008759 to Alpha-ketoglutarate dehydrogenase deficiency, OMIM:203740; oxoglutaricaciduria, MONDO:0008759
Likely inborn error of metabolism v4.29 OGDH Sarah Leigh Phenotypes for gene: OGDH were changed from 2-Oxoglutarate dehydrogenase deficiency (Disorders of the citric acid cycle); Alpha-ketoglutarate dehydrogenase deficiency, 203740 (1); (OXOGLUTARIC ACIDURIA); Alpha-ketoglutarate dehydrogenase deficiency, 203740 to Alpha-ketoglutarate dehydrogenase deficiency, OMIM:203740; oxoglutaricaciduria, MONDO:0008759
Undiagnosed metabolic disorders v1.586 OGDH Sarah Leigh Mode of inheritance for gene: OGDH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Undiagnosed metabolic disorders v1.585 OGDH Sarah Leigh Phenotypes for gene: OGDH were changed from 2-Oxoglutarate dehydrogenase deficiency (Disorders of the citric acid cycle); Alpha-ketoglutarate dehydrogenase deficiency, 203740; (OXOGLUTARIC ACIDURIA) to Alpha-ketoglutarate dehydrogenase deficiency, OMIM:203740; oxoglutaricaciduria, MONDO:0008759
Mitochondrial disorders v4.29 OGDH Sarah Leigh Phenotypes for gene: OGDH were changed from Alpha-ketoglutarate dehydrogenase deficiency OMIM:203740; oxoglutaricaciduria MONDO:0008759 to Alpha-ketoglutarate dehydrogenase deficiency, OMIM:203740; oxoglutaricaciduria, MONDO:0008759
Mitochondrial disorders v4.28 OGDH Sarah Leigh Publications for gene: OGDH were set to 32383294
Likely inborn error of metabolism v4.28 OGDH Sarah Leigh Publications for gene: OGDH were set to 27604308
Undiagnosed metabolic disorders v1.584 OGDH Sarah Leigh Publications for gene: OGDH were set to 27604308
Intellectual disability v5.107 ITPR1 Tracy Lester edited their review of gene: ITPR1: Added comment: PMID:29925855 - All 7 EOA patients with ITPR1 de novo variants (3 from cohort #1; 4 from cohort #2) presented with infantile onset cerebellar ataxia starting before the age of 2 years, including delayed motor milestones (Table 2). Cognitive deficits of variable degree were observed in 3 out of 4 patients where this information was available, reaching from only mild dyscalculia (P2) to severe intellectual disability with a speech vocabulary of only a few words (P7 at age 12 years). In contrast, patient P1 showed normal intelligence with an IQ of 97.

PMID:27108797 - Here, we report that both recessive and dominant ITPR1 mutations cause Gillespie syndrome. ITPR1 is a predominant isoform in the brain among the three types of ITPRs and is strongly expressed in cerebellar Purkinje cells.31 Mice with complete homozygosity for Itpr1 ablation suffer from severe epilepsy and ataxia and die either in utero or before weaning.32 Consistently, ITPR1 mutations have been reported to cause cerebellar diseases including late-onset spinocerebellar ataxia type 15 (SCA15 [MIM: 606658]),33 congenital nonprogressive spinocerebellar ataxia and mild cognitive impairment (SCA29 [MIM: 117360]),34 infantile-onset cerebellar ataxia with mild cognitive deficit,35 and childhood-onset ataxic cerebellar palsy with moderate intellectual disability36 (see ITPR1 schematic diagram in Figure 3A).
Affected individuals had similar iris anomalies and neonatal ataxia with progressive cerebellar atrophy (Figure 2). Moderate to severe intellectual disabilities were noted in the three individuals with recessive mutations (F1:II1, F2:II1, and F3:II1; Table 1). In contrast, the affected individual F4:II1 aged 18 years and harboring the de novo c.7687_7689del mutation was reported to have normal intelligence (Table 1).

As de novo variants are associated with ID/DD the inheritance should be updated to be BOTH AD and AR.; Set current diagnostic: yes
Fetal anomalies v3.73 MYL9 Arina Puzriakova Phenotypes for gene: MYL9 were changed from Megacystis Microcolon Intestinal Hypoperistalsis Syndrome (MMIH) to Megacystis-microcolon-intestinal hypoperistalsis syndrome 4, OMIM:619365
Intellectual disability v5.107 ITPR1 Tracy Lester reviewed gene: ITPR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29925855, 27108797; Phenotypes: developmental delay, intellectual disability, hypotonia, ataxia, cerebellar malformatons; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mosaic skin disorders - Deep sequencing v2.1 PTCH1 Tom Cullup gene: PTCH1 was added
gene: PTCH1 was added to Mosaic skin disorders - deep sequencing. Sources: Expert list
Mode of inheritance for gene: PTCH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PTCH1 were set to Gorlin syndrome / basal cell naevus syndrome
Penetrance for gene: PTCH1 were set to unknown
Review for gene: PTCH1 was set to GREEN
Added comment: Well established cause of Gorlin / BCN syndrome. Need to add to mosaic panel in order that mosaic patients / presentations can be accurately diagnosed - current existing indication (R214) does not include low-level variant analysis.
Sources: Expert list
Mosaic skin disorders - Deep sequencing v2.1 ARAF Tom Cullup gene: ARAF was added
gene: ARAF was added to Mosaic skin disorders - deep sequencing. Sources: Expert list
Mode of inheritance for gene: ARAF was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: ARAF were set to 31263281
Phenotypes for gene: ARAF were set to central conducting lymphatic anomaly
Penetrance for gene: ARAF were set to unknown
Mode of pathogenicity for gene: ARAF was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: ARAF was set to GREEN
Added comment: Two patients described in Li et al with lymphatic anomaly, with same activating missense; functional studies support activating effect including zebrafish model.
Sources: Expert list
Mosaic skin disorders - Deep sequencing v2.1 EGFR Tom Cullup gene: EGFR was added
gene: EGFR was added to Mosaic skin disorders - deep sequencing. Sources: Expert list
Mode of inheritance for gene: EGFR was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EGFR were set to 31745974
Phenotypes for gene: EGFR were set to nonepidermolytic keratinocytic epidermal naevus
Penetrance for gene: EGFR were set to unknown
Mode of pathogenicity for gene: EGFR was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: EGFR was set to AMBER
Added comment: Insufficient evidence for green rating, but compelling evidence from publication of single case, and important to be able to analyse in phenotypically appropriate cases as an amber gene.
Sources: Expert list
Mosaic skin disorders - Deep sequencing v2.1 GNB2 Tom Cullup reviewed gene: GNB2: Rating: AMBER; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 34124757; Phenotypes: Sturge-Weber syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Retinal disorders v4.7 LAMP2 Siying Lin gene: LAMP2 was added
gene: LAMP2 was added to Retinal disorders. Sources: Literature
Mode of inheritance for gene: LAMP2 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: LAMP2 were set to (PMID: 16751040; 32533651; 36288619; 22290069; 32890081; 26398689)
Phenotypes for gene: LAMP2 were set to Pigmentary retinopathy
Mode of pathogenicity for gene: LAMP2 was set to Other
Review for gene: LAMP2 was set to GREEN
Added comment: Several reports in literature identifying pigmentary retinopathy as part of the phenotypic spectrum in patients with Danon disease (female carriers less severely affected)
Sources: Literature
Hereditary neuropathy v1.466 MYO9B Dmitrijs Rots gene: MYO9B was added
gene: MYO9B was added to Hereditary neuropathy. Sources: Literature
Mode of inheritance for gene: MYO9B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYO9B were set to 36260368
Phenotypes for gene: MYO9B were set to CMT2
Penetrance for gene: MYO9B were set to Complete
Review for gene: MYO9B was set to GREEN
Added comment: 2 families with 4 affected cases + functional studies reported in 36260368
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.16 BCL11B Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: BCL11B.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.16 BCL11B Achchuthan Shanmugasundram Phenotypes for gene: BCL11B were changed from Craniosynostosis and global developmental delay to Intellectual developmental disorder with dysmorphic facies, speech delay, and T-cell abnormalities, OMIM:618092; Craniosynostosis, MONDO:0015469
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.15 BCL11B Achchuthan Shanmugasundram Publications for gene: BCL11B were set to 36275064; 310673176; 34900871; 36512050; 36470856
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.14 BCL11B Achchuthan Shanmugasundram Classified gene: BCL11B as Amber List (moderate evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.14 BCL11B Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Helen Lord (Oxford Medical Genetics Laboratories) and Rebecca Tooze (University of Oxford), there is sufficient number of cases (both published and unpublished) and supporting functional evidence for this gene to be promoted to GREEN in the next GMS update.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.14 BCL11B Achchuthan Shanmugasundram Gene: bcl11b has been classified as Amber List (Moderate Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.13 BCL11B Achchuthan Shanmugasundram reviewed gene: BCL11B: Rating: GREEN; Mode of pathogenicity: None; Publications: 31067316, 34900871, 36275064, 36470856, 36512050, 36980886; Phenotypes: Intellectual developmental disorder with dysmorphic facies, speech delay, and T-cell abnormalities, OMIM:618092, Craniosynostosis, MONDO:0015469; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.13 ARID1B Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: ARID1B.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.13 ARID1B Achchuthan Shanmugasundram Phenotypes for gene: ARID1B were changed from Coffin-Siris syndrome 1, OMIM:135900 to Coffin-Siris syndrome 1, OMIM:135900
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.12 ARID1B Achchuthan Shanmugasundram Phenotypes for gene: ARID1B were changed from to Coffin-Siris syndrome 1, OMIM:135900
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.11 ARID1B Achchuthan Shanmugasundram Publications for gene: ARID1B were set to
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.10 ARID1B Achchuthan Shanmugasundram Classified gene: ARID1B as Amber List (moderate evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.10 ARID1B Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Rebecca Tooze (University of Oxford), there is sufficient evidence (>3 unrelated cases) for this gene to be promoted to GREEN at the next GMS update.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.10 ARID1B Achchuthan Shanmugasundram Gene: arid1b has been classified as Amber List (Moderate Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.9 ARID1B Achchuthan Shanmugasundram reviewed gene: ARID1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 27474218, 32530565, 34429528, 36118902, 36980886; Phenotypes: Coffin-Siris syndrome 1, OMIM:135900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.9 AHDC1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: AHDC1.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.9 AHDC1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There are three unrelated cases of Xia-Gibbs syndrome reported with craniosynostosis as one of their clinical manifestations. Hence, this gene can be promoted to GREEN in the next major review.; to: Comment on list classification: There are three unrelated cases of Xia-Gibbs syndrome reported with craniosynostosis as one of their clinical manifestations and they all had different heterozygous variants. Hence, this gene can be promoted to GREEN in the next GMS update.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.9 AHDC1 Achchuthan Shanmugasundram Classified gene: AHDC1 as Amber List (moderate evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.9 AHDC1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are three unrelated cases of Xia-Gibbs syndrome reported with craniosynostosis as one of their clinical manifestations. Hence, this gene can be promoted to GREEN in the next major review.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.9 AHDC1 Achchuthan Shanmugasundram Gene: ahdc1 has been classified as Amber List (Moderate Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.8 AHDC1 Achchuthan Shanmugasundram changed review comment from: PMID:27884935 reported whole exome and genome sequencing analysis in a cohort of patients with undiagnosed craniosynostosis and identified one patient with a de novo variant (c.2373_2374delTG/ p.Cys791fs*57) in AHDC1. In addition to bicoronal and metopic craniosynostosis, the patient also had moderate developmental delay and hoarse cry.

PMID:30152016 reported the clinical phenotypes of five patients diagnosed with AHDC1-related Xia-Gibbs syndrome. Out of these five cases, one patient presented with bicoronal craniosynostosis in addition to intellectual disability and speech and motor delay and harboured a different heterozygous variant in AHDC1 (c.2473C > T/ p.Gln825*).

PMID:30858058 reported a two-year-old girl with developmental delay, brain anomalies, laryngomalacia and craniosynostosis and she was identified with a heterozygous variant (c.4370 A>G/ p.Asp1457Gly) in AHDC1.; to: A subset of patients with Xia-Gibbs syndrome (MIM #615829) presented with craniosynostosis as part of their clinical phenotype.

PMID:27884935 reported whole exome and genome sequencing analysis in a cohort of patients with undiagnosed craniosynostosis and identified one patient with a de novo variant (c.2373_2374delTG/ p.Cys791fs*57) in AHDC1. In addition to bicoronal and metopic craniosynostosis, the patient also had moderate developmental delay and hoarse cry.

PMID:30152016 reported the clinical phenotypes of five patients diagnosed with AHDC1-related Xia-Gibbs syndrome. Out of these five cases, one patient presented with bicoronal craniosynostosis in addition to intellectual disability and speech and motor delay and harboured a different heterozygous variant in AHDC1 (c.2473C > T/ p.Gln825*).

PMID:30858058 reported a two-year-old girl with developmental delay, brain anomalies, laryngomalacia and craniosynostosis and she was identified with a heterozygous variant (c.4370 A>G/ p.Asp1457Gly) in AHDC1.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.8 AHDC1 Achchuthan Shanmugasundram Mode of inheritance for gene: AHDC1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.7 AHDC1 Achchuthan Shanmugasundram Publications for gene: AHDC1 were set to
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.6 AHDC1 Achchuthan Shanmugasundram Phenotypes for gene: AHDC1 were changed from Xia-Gibbs syndrome 615829 to Xia-Gibbs syndrome, OMIM:615829
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.5 AHDC1 Achchuthan Shanmugasundram reviewed gene: AHDC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27884935, 30152016, 30858058; Phenotypes: Xia-Gibbs syndrome, OMIM:615829; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.5 ADAMTSL4 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: ADAMTSL4.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.5 ADAMTSL4 Achchuthan Shanmugasundram Classified gene: ADAMTSL4 as Amber List (moderate evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.5 ADAMTSL4 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next GMS update.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.5 ADAMTSL4 Achchuthan Shanmugasundram Gene: adamtsl4 has been classified as Amber List (Moderate Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.4 ADAMTSL4 Achchuthan Shanmugasundram Phenotypes for gene: ADAMTSL4 were changed from Ectopia lentis 225200/225100 to Ectopia lentis 225200/225100; craniosynostosis with ectopia lentis, MONDO:0011347
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.3 ADAMTSL4 Achchuthan Shanmugasundram Publications for gene: ADAMTSL4 were set to 10215540; 20702823; 22871183; 28642162; 35378950
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.2 ADAMTSL4 Achchuthan Shanmugasundram Publications for gene: ADAMTSL4 were set to 22871183; 20702823
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.1 ADAMTSL4 Achchuthan Shanmugasundram changed review comment from: PMID:20702823 reported 10 affected individuals from five unrelated Norwegian families with homozygous variants (c.767_786del/ p.Gln256Profs∗38) and they presented with ectopia lentis et pupillae. All these patients were surgically corrected for craniosynostosis.

PMID:22871183 reported a patient with right coronal synostosis and bilateral ectopia lentis, who harboured the same homozygous deletion variant. The proband's mother, father and one sibling are heterozygous carriers of the variant.

PMID:28642162 reported a Dutch family with monozygotic twins harbouring compound heterozygous variants (c.767_786del/ p.Gln256Profs∗38 & c.2254C > T/ p.Gln752∗) and both presented with craniosynostosis and ectopia lentis.

PMID:35378950 reported two unrelated families with craniosynostosis and ectopia lentis. Family 1’s proband is compound heterozygous (c.767_786del & c.2177 + 3_2177 + ) and family 2 has two homozygous affected siblings with c.767_786del, however the older sister did not have craniosynostosis (ectopia lentis only).; to: PMID:20702823 reported 10 affected individuals from five unrelated Norwegian families with homozygous variants (c.767_786del/ p.Gln256Profs∗38) and they presented with ectopia lentis et pupillae. All these patients were surgically corrected for craniosynostosis.

PMID:22871183 reported a patient with right coronal synostosis and bilateral ectopia lentis, who harboured the same homozygous deletion variant. The proband's mother, father and one sibling are heterozygous carriers of the variant.

PMID:28642162 reported a Dutch family with monozygotic twins harbouring compound heterozygous variants (c.767_786del/ p.Gln256Profs∗38 & c.2254C > T/ p.Gln752∗) and both presented with craniosynostosis and ectopia lentis.

PMID:35378950 reported two unrelated families with craniosynostosis and ectopia lentis. Family 1’s proband is compound heterozygous (c.767_786del & c.2177 + 3_2177 + ) and family 2 has two homozygous affected siblings with c.767_786del, however the older sister did not have craniosynostosis (ectopia lentis only).
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.1 ADAMTSL4 Achchuthan Shanmugasundram reviewed gene: ADAMTSL4: Rating: GREEN; Mode of pathogenicity: None; Publications: 10215540, 20702823, 22871183, 28642162, 35378950; Phenotypes: craniosynostosis with ectopia lentis, MONDO:0011347; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.72 SCUBE3 Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: SCUBE3.
Tag Q2_23_NHS_review tag was added to gene: SCUBE3.
Fetal anomalies v3.72 RAB11A Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: RAB11A.
Tag Q2_23_NHS_review tag was added to gene: RAB11A.
Fetal anomalies v3.72 ZMYM2 Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: ZMYM2.
Tag Q2_23_NHS_review tag was added to gene: ZMYM2.
Fetal anomalies v3.72 LRIG2 Arina Puzriakova Phenotypes for gene: LRIG2 were changed from UROFACIAL SYNDROME; Urofacial syndrome 2, OMIM:615112 to Urofacial syndrome 2, OMIM:615112
Fetal anomalies v3.71 AGTR1 Arina Puzriakova Publications for gene: AGTR1 were set to
Fetal anomalies v3.70 AGTR1 Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: AGTR1.
Tag Q2_23_NHS_review tag was added to gene: AGTR1.
Fetal anomalies v3.70 CLCN4 Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: CLCN4.
Tag Q2_23_NHS_review tag was added to gene: CLCN4.
Fetal anomalies v3.70 MECOM Arina Puzriakova Phenotypes for gene: MECOM were changed from Radioulnar Synostosis with Amegakaryocytic Thrombocytopenia; Radioulnar synostosis with amegakaryocytic thrombocytopenia 2, OMIM:616738 to Radioulnar synostosis with amegakaryocytic thrombocytopenia 2, OMIM:616738
Fetal anomalies v3.69 MECOM Arina Puzriakova Publications for gene: MECOM were set to
Fetal anomalies v3.68 MECOM Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: MECOM.
Tag Q2_23_NHS_review tag was added to gene: MECOM.
Fetal anomalies v3.68 WARS2 Arina Puzriakova Publications for gene: WARS2 were set to
Fetal anomalies v3.67 VARS2 Arina Puzriakova Publications for gene: VARS2 were set to
Fetal anomalies v3.66 UQCRFS1 Arina Puzriakova Publications for gene: UQCRFS1 were set to
Fetal anomalies v3.65 UQCRFS1 Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: UQCRFS1.
Tag Q2_23_NHS_review tag was added to gene: UQCRFS1.
Fetal anomalies v3.65 UQCC2 Arina Puzriakova Publications for gene: UQCC2 were set to
Fetal anomalies v3.64 TXN2 Arina Puzriakova Publications for gene: TXN2 were set to
Fetal anomalies v3.63 TRMU Arina Puzriakova Publications for gene: TRMU were set to
Fetal anomalies v3.62 TRIT1 Arina Puzriakova Publications for gene: TRIT1 were set to
Fetal anomalies v3.61 TMEM65 Arina Puzriakova Publications for gene: TMEM65 were set to
Fetal anomalies v3.60 TK2 Arina Puzriakova Tag watchlist was removed from gene: TK2.
Tag Q2_23_promote_green tag was added to gene: TK2.
Tag Q2_23_NHS_review tag was added to gene: TK2.
Fetal anomalies v3.60 SUCLA2 Arina Puzriakova Publications for gene: SUCLA2 were set to
Fetal anomalies v3.59 SLC25A46 Arina Puzriakova Publications for gene: SLC25A46 were set to
Fetal anomalies v3.58 SLC25A46 Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: SLC25A46.
Tag Q2_23_NHS_review tag was added to gene: SLC25A46.
Fetal anomalies v3.58 SLC25A1 Arina Puzriakova Publications for gene: SLC25A1 were set to
Fetal anomalies v3.57 SFXN4 Arina Puzriakova Publications for gene: SFXN4 were set to
Fetal anomalies v3.56 SDHD Arina Puzriakova Publications for gene: SDHD were set to
Fetal anomalies v3.55 RMND1 Arina Puzriakova Phenotypes for gene: RMND1 were changed from ENCEPHALOPATHY ASSOCIATED WITH MULTIPLE OXIDATIVE PHOSPHORYLATION COMPLEX DEFICIENCIES AND A MITOCHONDRIAL TRANSLATION DEFECT; Combined oxidative phosphorylation deficiency 11, OMIM:614922 to Combined oxidative phosphorylation deficiency 11, OMIM:614922
Fetal anomalies v3.54 RMND1 Arina Puzriakova Publications for gene: RMND1 were set to
Fetal anomalies v3.53 RMND1 Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: RMND1.
Tag Q2_23_NHS_review tag was added to gene: RMND1.
Fetal anomalies v3.53 QRSL1 Arina Puzriakova Publications for gene: QRSL1 were set to
Fetal anomalies v3.52 QRSL1 Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: QRSL1.
Tag Q2_23_NHS_review tag was added to gene: QRSL1.
Fetal anomalies v3.52 POLG Arina Puzriakova Phenotypes for gene: POLG were changed from Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE), OMIM:607459; Mitochondrial DNA depletion syndrome 4A (Alpers type), OMIM:203700; MITOCHONDRIAL DNA DEPLETION SYNDROME 4A; Mitochondrial DNA depletion syndrome 4B (MNGIE type), OMIM:613662 to Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE), OMIM:607459; Mitochondrial DNA depletion syndrome 4A (Alpers type), OMIM:203700; Mitochondrial DNA depletion syndrome 4B (MNGIE type), OMIM:613662
Fetal anomalies v3.51 POLG Arina Puzriakova Publications for gene: POLG were set to
Fetal anomalies v3.50 PNPLA8 Arina Puzriakova Publications for gene: PNPLA8 were set to
Fetal anomalies v3.49 PNPLA8 Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: PNPLA8.
Tag Q2_23_NHS_review tag was added to gene: PNPLA8.
Fetal anomalies v3.49 PET100 Arina Puzriakova Phenotypes for gene: PET100 were changed from MITOCHONDRIAL COMPLEX IV DEFICIENCY; Mitochondrial complex IV deficiency, nuclear type 12, OMIM:619055 to Mitochondrial complex IV deficiency, nuclear type 12, OMIM:619055
Fetal anomalies v3.48 PET100 Arina Puzriakova Publications for gene: PET100 were set to
Fetal anomalies v3.47 PET100 Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: PET100.
Tag Q2_23_NHS_review tag was added to gene: PET100.
Fetal anomalies v3.47 PDHX Arina Puzriakova Phenotypes for gene: PDHX were changed from LACTICACIDEMIA DUE TO PDX1 DEFICIENCY; Lacticacidemia due to PDX1 deficiency, OMIM:245349 to Lacticacidemia due to PDX1 deficiency, OMIM:245349
Fetal anomalies v3.46 PDHX Arina Puzriakova Publications for gene: PDHX were set to
Fetal anomalies v3.45 PDHX Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: PDHX.
Tag Q2_23_NHS_review tag was added to gene: PDHX.
Fetal anomalies v3.45 PDHB Arina Puzriakova Phenotypes for gene: PDHB were changed from Pyruvate dehydrogenase E1-beta deficiency, OMIM:614111; Pyruvate dehydrogenase E1-beta deficiency, 614111 to Pyruvate dehydrogenase E1-beta deficiency, OMIM:614111
Fetal anomalies v3.44 PDHB Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: PDHB.
Tag Q2_23_NHS_review tag was added to gene: PDHB.
Fetal anomalies v3.44 PC Arina Puzriakova Phenotypes for gene: PC were changed from Pyruvate carboxylase deficiency, OMIM:266150; PYRUVATE CARBOXYLASE DEFICIENCY to Pyruvate carboxylase deficiency, OMIM:266150
Fetal anomalies v3.43 PC Arina Puzriakova Publications for gene: PC were set to
Fetal anomalies v3.42 PC Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: PC.
Tag Q2_23_NHS_review tag was added to gene: PC.
Fetal anomalies v3.42 NDUFV2 Arina Puzriakova Publications for gene: NDUFV2 were set to
Fetal anomalies v3.41 NDUFS1 Arina Puzriakova Phenotypes for gene: NDUFS1 were changed from Mitochondrial complex I deficiency, nuclear type 5, OMIM:618226; MITOCHONDRIAL RESPIRATORY CHAIN COMPLEX I DEFICIENCY; LEIGH SYNDROME to Mitochondrial complex I deficiency, nuclear type 5, OMIM:618226
Fetal anomalies v3.40 NDUFS1 Arina Puzriakova Publications for gene: NDUFS1 were set to
Fetal anomalies v3.39 NDUFS1 Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: NDUFS1.
Tag Q2_23_NHS_review tag was added to gene: NDUFS1.
Fetal anomalies v3.39 NDUFC2 Arina Puzriakova Publications for gene: NDUFC2 were set to
Fetal anomalies v3.38 NDUFB7 Arina Puzriakova Publications for gene: NDUFB7 were set to
Fetal anomalies v3.37 NDUFB3 Arina Puzriakova Publications for gene: NDUFB3 were set to
Fetal anomalies v3.36 NDUFB3 Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: NDUFB3.
Tag Q2_23_NHS_review tag was added to gene: NDUFB3.
Fetal anomalies v3.36 NDUFB11 Arina Puzriakova Phenotypes for gene: NDUFB11 were changed from Linear skin defects with multiple congenital anomalies 3, OMIM:300952; Cardiomyopathy; Agenesis of corpus callosum (ACC) to ?Mitochondrial complex I deficiency, nuclear type 30, OMIM:301021; Linear skin defects with multiple congenital anomalies 3, OMIM:300952; Cardiomyopathy; Agenesis of corpus callosum (ACC)
Fetal anomalies v3.35 NDUFB10 Arina Puzriakova Phenotypes for gene: NDUFB10 were changed from Mitochondrial complex I deficiency, nuclear type 35, OMIM:619003; Mitochondrial complex I deficiency, nuclear type 35 , OMIM:619003 to Mitochondrial complex I deficiency, nuclear type 35, OMIM:619003
Fetal anomalies v3.34 NDUFB10 Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: NDUFB10.
Tag Q2_23_NHS_review tag was added to gene: NDUFB10.
Fetal anomalies v3.34 NDUFAF8 Arina Puzriakova Publications for gene: NDUFAF8 were set to
Fetal anomalies v3.33 NDUFAF8 Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: NDUFAF8.
Tag Q2_23_NHS_review tag was added to gene: NDUFAF8.
Fetal anomalies v3.33 NDUFA6 Arina Puzriakova Publications for gene: NDUFA6 were set to
Fetal anomalies v3.32 NDUFA6 Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: NDUFA6.
Tag Q2_23_NHS_review tag was added to gene: NDUFA6.
Fetal anomalies v3.32 NDUFA12 Arina Puzriakova Publications for gene: NDUFA12 were set to
Fetal anomalies v3.31 NADK2 Arina Puzriakova Publications for gene: NADK2 were set to
Fetal anomalies v3.30 MTPAP Arina Puzriakova Publications for gene: MTPAP were set to
Fetal anomalies v3.29 MTFMT Arina Puzriakova Publications for gene: MTFMT were set to
Fetal anomalies v3.28 MTFMT Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: MTFMT.
Tag Q2_23_NHS_review tag was added to gene: MTFMT.
Fetal anomalies v3.28 MRPS14 Arina Puzriakova Publications for gene: MRPS14 were set to
Fetal anomalies v3.27 MRPS14 Arina Puzriakova Tag to_be_confirmed_NHSE tag was added to gene: MRPS14.
Tag Q2_23_promote_green tag was added to gene: MRPS14.
Tag Q2_23_NHS_review tag was added to gene: MRPS14.
Fetal anomalies v3.27 MPC2 Arina Puzriakova Publications for gene: MPC2 were set to
Fetal anomalies v3.26 MPC1 Arina Puzriakova Publications for gene: MPC1 were set to
Fetal anomalies v3.25 IBA57 Arina Puzriakova Publications for gene: IBA57 were set to
Fetal anomalies v3.24 IBA57 Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: IBA57.
Tag Q2_23_NHS_review tag was added to gene: IBA57.
Fetal anomalies v3.24 GFM2 Arina Puzriakova Publications for gene: GFM2 were set to
Fetal anomalies v3.23 GATB Arina Puzriakova Publications for gene: GATB were set to
Fetal anomalies v3.22 GATB Arina Puzriakova Tag to_be_confirmed_NHSE tag was added to gene: GATB.
Tag Q2_23_promote_green tag was added to gene: GATB.
Tag Q2_23_NHS_review tag was added to gene: GATB.
Fetal anomalies v3.22 ECHS1 Arina Puzriakova Publications for gene: ECHS1 were set to
Fetal anomalies v3.21 ECHS1 Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: ECHS1.
Tag Q2_23_NHS_review tag was added to gene: ECHS1.
Fetal anomalies v3.21 EARS2 Arina Puzriakova Publications for gene: EARS2 were set to
Fetal anomalies v3.20 EARS2 Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: EARS2.
Tag Q2_23_NHS_review tag was added to gene: EARS2.
Palmoplantar keratodermas v3.2 SERPINB8 Tom Cullup gene: SERPINB8 was added
gene: SERPINB8 was added to Palmoplantar keratodermas. Sources: Expert list
Mode of inheritance for gene: SERPINB8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SERPINB8 were set to PubMed: 27476651
Phenotypes for gene: SERPINB8 were set to Peeling skin syndrome 5
Penetrance for gene: SERPINB8 were set to unknown
Review for gene: SERPINB8 was set to GREEN
Added comment: Recommend all peeling skin syndrome genes should be on R165 & R166
Sources: Expert list
Ichthyosis and erythrokeratoderma v3.3 SERPINB8 Tom Cullup gene: SERPINB8 was added
gene: SERPINB8 was added to Ichthyosis and erythrokeratoderma. Sources: Expert list
Mode of inheritance for gene: SERPINB8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SERPINB8 were set to PubMed: 27476651
Phenotypes for gene: SERPINB8 were set to Peeling skin syndrome 5
Penetrance for gene: SERPINB8 were set to unknown
Review for gene: SERPINB8 was set to GREEN
Added comment: Recommend all peeling skin syndrome genes should be on R165 & R166
Sources: Expert list
Fetal anomalies v3.20 DNA2 Arina Puzriakova Publications for gene: DNA2 were set to
Fetal anomalies v3.19 DNA2 Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: DNA2.
Tag Q2_23_NHS_review tag was added to gene: DNA2.
Fetal anomalies v3.19 DGUOK Arina Puzriakova Publications for gene: DGUOK were set to
Ichthyosis and erythrokeratoderma v3.3 TGM5 Tom Cullup gene: TGM5 was added
gene: TGM5 was added to Ichthyosis and erythrokeratoderma. Sources: Expert list
Mode of inheritance for gene: TGM5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TGM5 were set to PubMed: 16380904; 19440220; 20164844; 22036214
Phenotypes for gene: TGM5 were set to Peeling skin syndrome 2
Penetrance for gene: TGM5 were set to unknown
Review for gene: TGM5 was set to GREEN
Added comment: Recommend all peeling skin syndrome genes should be on R165 & R166
Sources: Expert list
Palmoplantar keratodermas v3.2 TGM5 Tom Cullup gene: TGM5 was added
gene: TGM5 was added to Palmoplantar keratodermas. Sources: Expert list
Mode of inheritance for gene: TGM5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TGM5 were set to PubMed: 16380904; 19440220; 20164844; 22036214
Phenotypes for gene: TGM5 were set to Peeling skin syndrome 2
Penetrance for gene: TGM5 were set to unknown
Review for gene: TGM5 was set to GREEN
Added comment: Recommend all peeling skin syndrome genes should be on R165 & R166
Sources: Expert list
Fetal anomalies v3.18 DARS2 Arina Puzriakova Phenotypes for gene: DARS2 were changed from LEUKOENCEPHALOPATHY WITH BRAINSTEM AND SPINAL CORD INVOLVEMENT AND LACTATE ELEVATION; Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, OMIM:611105 to Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, OMIM:611105
Fetal anomalies v3.17 DARS2 Arina Puzriakova Publications for gene: DARS2 were set to
Fetal anomalies v3.16 DARS2 Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: DARS2.
Tag Q2_23_NHS_review tag was added to gene: DARS2.
Fetal anomalies v3.16 COX14 Arina Puzriakova Publications for gene: COX14 were set to
Fetal anomalies v3.15 COQ7 Arina Puzriakova Publications for gene: COQ7 were set to
Fetal anomalies v3.14 COQ7 Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: COQ7.
Tag Q2_23_NHS_review tag was added to gene: COQ7.
Ichthyosis and erythrokeratoderma v3.3 CDSN Tom Cullup gene: CDSN was added
gene: CDSN was added to Ichthyosis and erythrokeratoderma. Sources: Expert list
Mode of inheritance for gene: CDSN was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: CDSN were set to PubMed: 21191406; 12754508; 23957618
Phenotypes for gene: CDSN were set to Hypotrichosis 2; Peeling skin syndrome 1
Penetrance for gene: CDSN were set to unknown
Review for gene: CDSN was set to GREEN
Added comment: Recommend all peeling skin syndrome genes should be on R165 & R166
Sources: Expert list
Fetal anomalies v3.14 COA6 Arina Puzriakova Publications for gene: COA6 were set to
Fetal anomalies v3.13 COA6 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: COA6.
Tag Q2_23_NHS_review was removed from gene: COA6.
Fetal anomalies v3.13 COA6 Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: COA6.
Tag Q2_23_NHS_review tag was added to gene: COA6.
Fetal anomalies v3.13 C1QBP Arina Puzriakova Publications for gene: C1QBP were set to 32304219
Fetal anomalies v3.12 C1QBP Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: C1QBP.
Tag Q2_23_NHS_review tag was added to gene: C1QBP.
Fetal anomalies v3.12 C19orf70 Arina Puzriakova Publications for gene: C19orf70 were set to
Ichthyosis and erythrokeratoderma v3.3 CSTA Tom Cullup gene: CSTA was added
gene: CSTA was added to Ichthyosis and erythrokeratoderma. Sources: Expert list
Mode of inheritance for gene: CSTA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CSTA were set to 21944047; 23534700
Phenotypes for gene: CSTA were set to peeling skin syndrome-4 (PSS4)
Penetrance for gene: CSTA were set to unknown
Review for gene: CSTA was set to GREEN
Added comment: Recommend all peeling skin syndrome genes should be on R165 & R166
Sources: Expert list
Fetal anomalies v3.11 ATP5O Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: ATP5O.
Tag Q2_23_NHS_review tag was added to gene: ATP5O.
Fetal anomalies v3.11 ATP5O Arina Puzriakova Tag Q2_23_promote_green was removed from gene: ATP5O.
Tag Q2_23_NHS_review was removed from gene: ATP5O.
Tag new-gene-name tag was added to gene: ATP5O.
Fetal anomalies v3.11 C19orf70 Arina Puzriakova Tag new-gene-name tag was added to gene: C19orf70.
Fetal anomalies v3.11 C19orf70 Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: C19orf70.
Tag Q2_23_NHS_review tag was added to gene: C19orf70.
Fetal anomalies v3.11 ATP5O Arina Puzriakova Publications for gene: ATP5O were set to
Fetal anomalies v3.10 ATP5O Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: ATP5O.
Tag Q2_23_NHS_review tag was added to gene: ATP5O.
Palmoplantar keratodermas v3.2 FLG2 Tom Cullup gene: FLG2 was added
gene: FLG2 was added to Palmoplantar keratodermas. Sources: Expert list
Mode of inheritance for gene: FLG2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FLG2 were set to PubMed: 28884927; 29505760
Phenotypes for gene: FLG2 were set to peeling skin syndrome-6 (PSS6) (MIM 618084)
Penetrance for gene: FLG2 were set to unknown
Review for gene: FLG2 was set to GREEN
Added comment: Recommend all peeling skin syndrome genes should be on R165 & R166
Sources: Expert list
Fetal anomalies v3.10 AARS2 Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: AARS2.
Tag Q2_23_NHS_review tag was added to gene: AARS2.
Fetal anomalies v3.10 AARS2 Arina Puzriakova Phenotypes for gene: AARS2 were changed from Leukoencephalopathy, progressive, with ovarian failure, OMIM:615889; fetal hydrops; cardiomyopathy; polyhydramnios; Combined oxidative phosphorylation deficiency 8, OMIM:614096; pulmonary effusion to Leukoencephalopathy, progressive, with ovarian failure, OMIM:615889; Combined oxidative phosphorylation deficiency 8, OMIM:614096; fetal hydrops; cardiomyopathy; polyhydramnios; pulmonary effusion
Fetal anomalies v3.9 AARS2 Arina Puzriakova Publications for gene: AARS2 were set to 30819764
Palmoplantar keratodermas v3.2 FAM83G Tom Cullup reviewed gene: FAM83G: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 29138053, 31656861, 29963719; Phenotypes: palmoplantar keratoderma, leukonychia, and exuberant curly scalp hair; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Palmoplantar keratoderma and erythrokeratodermas v1.28 FAM83G Tom Cullup reviewed gene: FAM83G: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 29138053, 31656861, 29963719; Phenotypes: palmoplantar keratoderma, leukonychia, and exuberant curly scalp hair; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ichthyosis and erythrokeratoderma v3.3 FAM83G Tom Cullup reviewed gene: FAM83G: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 29138053, 31656861, 29963719; Phenotypes: palmoplantar keratoderma, leukonychia, and exuberant curly scalp hair; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 SCUBE3 Stephanie Allen commented on gene: SCUBE3
Fetal anomalies v3.8 RAB11A Stephanie Allen commented on gene: RAB11A
Fetal anomalies v3.8 ZMYM2 Stephanie Allen commented on gene: ZMYM2: This gene and phenotype were reviewed during a meeting on 2nd March 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, (North Thames GLH), and Stephanie Allen, Denise Williams, Anna de Burca and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.
Fetal anomalies v3.8 LRIG2 Stephanie Allen commented on gene: LRIG2: This gene and phenotype were reviewed during a meeting on 23rd Feb 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Natalie Chandler (North Thames GLH), and Stephanie Allen, Esther Kinning and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Amber gene.
Fetal anomalies v3.8 AGTR1 Stephanie Allen commented on gene: AGTR1: This gene and phenotype were reviewed during a meeting on 23rd Feb 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Natalie Chandler (North Thames GLH), and Stephanie Allen, Esther Kinning and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.
Fetal anomalies v3.8 CLCN4 Stephanie Allen commented on gene: CLCN4: This gene and phenotype were reviewed during a meeting on 2nd March 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, (North Thames GLH), and Stephanie Allen, Denise Williams, Anna de Burca and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.
Fetal anomalies v3.8 MECOM Stephanie Allen commented on gene: MECOM: This gene and phenotype were reviewed during a meeting on 2nd March 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, (North Thames GLH), and Stephanie Allen, Denise Williams, Anna de Burca and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.
Fetal anomalies v3.8 TRMU Stephanie Allen commented on gene: TRMU: This gene and phenotype were reviewed during a meeting on 2nd March 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, (North Thames GLH), and Stephanie Allen, Denise Williams, Anna de Burca and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Red gene.
Fetal anomalies v3.8 NDUFA12 Stephanie Allen commented on gene: NDUFA12: This gene and phenotype were reviewed during a meeting on 2nd March 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, (North Thames GLH), and Stephanie Allen, Denise Williams, Anna de Burca and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Red gene.
Fetal anomalies v3.8 WARS2 Stephanie Allen commented on gene: WARS2: This gene and phenotype were reviewed during a meeting on 2nd March 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, (North Thames GLH), and Stephanie Allen, Denise Williams, Anna de Burca and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Amber gene.
Fetal anomalies v3.8 VARS2 Stephanie Allen commented on gene: VARS2: This gene and phenotype were reviewed during a meeting on 2nd March 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, (North Thames GLH), and Stephanie Allen, Denise Williams, Anna de Burca and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Amber gene.
Fetal anomalies v3.8 UQCC2 Stephanie Allen commented on gene: UQCC2: This gene and phenotype were reviewed during a meeting on 2nd March 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, (North Thames GLH), and Stephanie Allen, Denise Williams, Anna de Burca and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Amber gene.
Fetal anomalies v3.8 TXN2 Stephanie Allen commented on gene: TXN2: This gene and phenotype were reviewed during a meeting on 2nd March 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, (North Thames GLH), and Stephanie Allen, Denise Williams, Anna de Burca and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Amber gene.
Fetal anomalies v3.8 TRIT1 Stephanie Allen commented on gene: TRIT1: This gene and phenotype were reviewed during a meeting on 2nd March 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, (North Thames GLH), and Stephanie Allen, Denise Williams, Anna de Burca and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Amber gene.
Fetal anomalies v3.8 TMEM65 Stephanie Allen commented on gene: TMEM65: This gene and phenotype were reviewed during a meeting on 2nd March 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, (North Thames GLH), and Stephanie Allen, Denise Williams, Anna de Burca and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Amber gene.
Fetal anomalies v3.8 POLG Stephanie Allen commented on gene: POLG: This gene and phenotype were reviewed during a meeting on 2nd March 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, (North Thames GLH), and Stephanie Allen, Denise Williams, Anna de Burca and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Amber gene.
Fetal anomalies v3.8 NDUFV2 Stephanie Allen commented on gene: NDUFV2: This gene and phenotype were reviewed during a meeting on 2nd March 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, (North Thames GLH), and Stephanie Allen, Denise Williams, Anna de Burca and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Amber gene.
Fetal anomalies v3.8 NDUFC2 Stephanie Allen commented on gene: NDUFC2: This gene and phenotype were reviewed during a meeting on 2nd March 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, (North Thames GLH), and Stephanie Allen, Denise Williams, Anna de Burca and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Amber gene.
Fetal anomalies v3.8 NDUFB7 Stephanie Allen commented on gene: NDUFB7: This gene and phenotype were reviewed during a meeting on 2nd March 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, (North Thames GLH), and Stephanie Allen, Denise Williams, Anna de Burca and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Amber gene.
Fetal anomalies v3.8 NADK2 Stephanie Allen commented on gene: NADK2: This gene and phenotype were reviewed during a meeting on 2nd March 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, (North Thames GLH), and Stephanie Allen, Denise Williams, Anna de Burca and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Amber gene.
Fetal anomalies v3.8 MTPAP Stephanie Allen commented on gene: MTPAP: This gene and phenotype were reviewed during a meeting on 2nd March 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, (North Thames GLH), and Stephanie Allen, Denise Williams, Anna de Burca and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Amber gene.
Fetal anomalies v3.8 UQCRFS1 Stephanie Allen commented on gene: UQCRFS1: This gene and phenotype were reviewed during a meeting on 2nd March 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, (North Thames GLH), and Stephanie Allen, Denise Williams, Anna de Burca and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.
Fetal anomalies v3.8 TK2 Stephanie Allen commented on gene: TK2: This gene and phenotype were reviewed during a meeting on 2nd March 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, (North Thames GLH), and Stephanie Allen, Denise Williams, Anna de Burca and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.
Fetal anomalies v3.8 PNPLA8 Stephanie Allen commented on gene: PNPLA8: This gene and phenotype were reviewed during a meeting on 2nd March 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, (North Thames GLH), and Stephanie Allen, Denise Williams, Anna de Burca and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.
Fetal anomalies v3.8 PET100 Stephanie Allen commented on gene: PET100: This gene and phenotype were reviewed during a meeting on 2nd March 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, (North Thames GLH), and Stephanie Allen, Denise Williams, Anna de Burca and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.
Fetal anomalies v3.8 PDHX Stephanie Allen commented on gene: PDHX: This gene and phenotype were reviewed during a meeting on 2nd March 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, (North Thames GLH), and Stephanie Allen, Denise Williams, Anna de Burca and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.
Fetal anomalies v3.8 PDHB Stephanie Allen commented on gene: PDHB: This gene and phenotype were reviewed during a meeting on 2nd March 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, (North Thames GLH), and Stephanie Allen, Denise Williams, Anna de Burca and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.
Fetal anomalies v3.8 PC Stephanie Allen commented on gene: PC: This gene and phenotype were reviewed during a meeting on 2nd March 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, (North Thames GLH), and Stephanie Allen, Denise Williams, Anna de Burca and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.
Fetal anomalies v3.8 NDUFS1 Stephanie Allen commented on gene: NDUFS1: This gene and phenotype were reviewed during a meeting on 2nd March 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, (North Thames GLH), and Stephanie Allen, Denise Williams, Anna de Burca and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.
Fetal anomalies v3.8 NDUFB3 Stephanie Allen commented on gene: NDUFB3: This gene and phenotype were reviewed during a meeting on 2nd March 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, (North Thames GLH), and Stephanie Allen, Denise Williams, Anna de Burca and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.
Fetal anomalies v3.8 NDUFB11 Stephanie Allen commented on gene: NDUFB11: This gene and phenotype were reviewed during a meeting on 2nd March 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, (North Thames GLH), and Stephanie Allen, Denise Williams, Anna de Burca and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.
Fetal anomalies v3.8 NDUFB10 Stephanie Allen commented on gene: NDUFB10: This gene and phenotype were reviewed during a meeting on 2nd March 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, (North Thames GLH), and Stephanie Allen, Denise Williams, Anna de Burca and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.
Fetal anomalies v3.8 NDUFAF8 Stephanie Allen commented on gene: NDUFAF8: This gene and phenotype were reviewed during a meeting on 2nd March 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, (North Thames GLH), and Stephanie Allen, Denise Williams, Anna de Burca and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.
Fetal anomalies v3.8 NDUFA6 Stephanie Allen commented on gene: NDUFA6: This gene and phenotype were reviewed during a meeting on 2nd March 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, (North Thames GLH), and Stephanie Allen, Denise Williams, Anna de Burca and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.
Fetal anomalies v3.8 MTFMT Stephanie Allen commented on gene: MTFMT: This gene and phenotype were reviewed during a meeting on 2nd March 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, (North Thames GLH), and Stephanie Allen, Denise Williams, Anna de Burca and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.
Fetal anomalies v3.8 MRPS14 Stephanie Allen commented on gene: MRPS14: This gene and phenotype were reviewed during a meeting on 2nd March 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, (North Thames GLH), and Stephanie Allen, Denise Williams, Anna de Burca and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.
Fetal anomalies v3.8 SDHD Stephanie Allen commented on gene: SDHD: This gene and phenotype were reviewed during a meeting on 23rd Feb 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Natalie Chandler (North Thames GLH), and Stephanie Allen, Esther Kinning and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Red gene.
Fetal anomalies v3.8 SUCLA2 Stephanie Allen commented on gene: SUCLA2: This gene and phenotype were reviewed during a meeting on 23rd Feb 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Natalie Chandler (North Thames GLH), and Stephanie Allen, Esther Kinning and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Amber gene.
Fetal anomalies v3.8 SLC25A1 Stephanie Allen commented on gene: SLC25A1: This gene and phenotype were reviewed during a meeting on 23rd Feb 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Natalie Chandler (North Thames GLH), and Stephanie Allen, Esther Kinning and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Amber gene.
Fetal anomalies v3.8 SFXN4 Stephanie Allen commented on gene: SFXN4: This gene and phenotype were reviewed during a meeting on 23rd Feb 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Natalie Chandler (North Thames GLH), and Stephanie Allen, Esther Kinning and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Amber gene.
Fetal anomalies v3.8 MPC2 Stephanie Allen commented on gene: MPC2: This gene and phenotype were reviewed during a meeting on 23rd Feb 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Natalie Chandler (North Thames GLH), and Stephanie Allen, Esther Kinning and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Amber gene.
Fetal anomalies v3.8 MPC1 Stephanie Allen commented on gene: MPC1: This gene and phenotype were reviewed during a meeting on 23rd Feb 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Natalie Chandler (North Thames GLH), and Stephanie Allen, Esther Kinning and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Amber gene.
Fetal anomalies v3.8 GFM2 Stephanie Allen commented on gene: GFM2: This gene and phenotype were reviewed during a meeting on 23rd Feb 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Natalie Chandler (North Thames GLH), and Stephanie Allen, Esther Kinning and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Amber gene.
Fetal anomalies v3.8 DGUOK Stephanie Allen commented on gene: DGUOK: This gene and phenotype were reviewed during a meeting on 23rd Feb 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Natalie Chandler (North Thames GLH), and Stephanie Allen, Esther Kinning and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Amber gene.
Fetal anomalies v3.8 COX14 Stephanie Allen commented on gene: COX14: This gene and phenotype were reviewed during a meeting on 23rd Feb 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Natalie Chandler (North Thames GLH), and Stephanie Allen, Esther Kinning and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Amber gene.
Fetal anomalies v3.8 COA6 Stephanie Allen commented on gene: COA6: This gene and phenotype were reviewed during a meeting on 23rd Feb 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Natalie Chandler (North Thames GLH), and Stephanie Allen, Esther Kinning and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Amber gene.
Fetal anomalies v3.8 SLC25A46 Stephanie Allen commented on gene: SLC25A46: This gene and phenotype were reviewed during a meeting on 23rd Feb 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Natalie Chandler (North Thames GLH), and Stephanie Allen, Esther Kinning and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.
Fetal anomalies v3.8 RMND1 Stephanie Allen commented on gene: RMND1: This gene and phenotype were reviewed during a meeting on 23rd Feb 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Natalie Chandler (North Thames GLH), and Stephanie Allen, Esther Kinning and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.
Fetal anomalies v3.8 QRSL1 Stephanie Allen commented on gene: QRSL1: This gene and phenotype were reviewed during a meeting on 23rd Feb 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Natalie Chandler (North Thames GLH), and Stephanie Allen, Esther Kinning and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.
Fetal anomalies v3.8 IBA57 Stephanie Allen commented on gene: IBA57: This gene and phenotype were reviewed during a meeting on 23rd Feb 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Natalie Chandler (North Thames GLH), and Stephanie Allen, Esther Kinning and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.
Fetal anomalies v3.8 GATB Stephanie Allen commented on gene: GATB: This gene and phenotype were reviewed during a meeting on 23rd Feb 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Natalie Chandler (North Thames GLH), and Stephanie Allen, Esther Kinning and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.
Fetal anomalies v3.8 ECHS1 Stephanie Allen commented on gene: ECHS1: This gene and phenotype were reviewed during a meeting on 23rd Feb 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Natalie Chandler (North Thames GLH), and Stephanie Allen, Esther Kinning and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.
Fetal anomalies v3.8 EARS2 Stephanie Allen commented on gene: EARS2: This gene and phenotype were reviewed during a meeting on 23rd Feb 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Natalie Chandler (North Thames GLH), and Stephanie Allen, Esther Kinning and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.
Fetal anomalies v3.8 DNA2 Stephanie Allen commented on gene: DNA2: This gene and phenotype were reviewed during a meeting on 23rd Feb 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Natalie Chandler (North Thames GLH), and Stephanie Allen, Esther Kinning and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.
Fetal anomalies v3.8 DARS2 Stephanie Allen commented on gene: DARS2: This gene and phenotype were reviewed during a meeting on 23rd Feb 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Natalie Chandler (North Thames GLH), and Stephanie Allen, Esther Kinning and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.
Fetal anomalies v3.8 COQ7 Stephanie Allen commented on gene: COQ7: This gene and phenotype were reviewed during a meeting on 23rd Feb 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Natalie Chandler (North Thames GLH), and Stephanie Allen, Esther Kinning and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.
Fetal anomalies v3.8 C1QBP Stephanie Allen commented on gene: C1QBP: This gene and phenotype were reviewed during a meeting on 23rd Feb 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Natalie Chandler (North Thames GLH), and Stephanie Allen, Esther Kinning and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.
Fetal anomalies v3.8 C19orf70 Stephanie Allen commented on gene: C19orf70: This gene and phenotype were reviewed during a meeting on 23rd Feb 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Natalie Chandler (North Thames GLH), and Stephanie Allen, Esther Kinning and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.
Fetal anomalies v3.8 ATP5O Stephanie Allen commented on gene: ATP5O: This gene and phenotype were reviewed during a meeting on 23rd Feb 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Natalie Chandler (North Thames GLH), and Stephanie Allen, Esther Kinning and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.
Fetal anomalies v3.8 AARS2 Stephanie Allen commented on gene: AARS2: This gene and phenotype were reviewed during a meeting on 23rd Feb 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Natalie Chandler (North Thames GLH), and Stephanie Allen, Esther Kinning and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.
Fetal anomalies v3.8 ZMYM2 Stephanie Allen reviewed gene: ZMYM2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities, OMIM:619522; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v3.8 LRIG2 Stephanie Allen reviewed gene: LRIG2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: Urofacial syndrome 2, OMIM:615112; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 AGTR1 Stephanie Allen reviewed gene: AGTR1: Rating: GREEN; Mode of pathogenicity: ; Publications: 16116425, 22095942; Phenotypes: Renal tubular dysgenesis, OMIM:267430; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 CLCN4 Stephanie Allen reviewed gene: CLCN4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Raynaud-Claes syndrome, OMIM:300114; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Fetal anomalies v3.8 MECOM Stephanie Allen reviewed gene: MECOM: Rating: GREEN; Mode of pathogenicity: ; Publications: 29540340, 26581901; Phenotypes: Radioulnar synostosis with amegakaryocytic thrombocytopenia 2, OMIM:616738; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v3.8 WARS2 Stephanie Allen reviewed gene: WARS2: Rating: AMBER; Mode of pathogenicity: ; Publications: 30920170, 28905505, 35074316, 29783990; Phenotypes: Neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures, OMIM:617710; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 VARS2 Stephanie Allen reviewed gene: VARS2: Rating: AMBER; Mode of pathogenicity: ; Publications: 33937156, 29314548, 29478218; Phenotypes: Combined oxidative phosphorylation deficiency 20, OMIM:615917; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 UQCRFS1 Stephanie Allen reviewed gene: UQCRFS1: Rating: GREEN; Mode of pathogenicity: ; Publications: 31883641; Phenotypes: Mitochondrial complex III deficiency, nuclear type 10, OMIM:618775; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 UQCC2 Stephanie Allen reviewed gene: UQCC2: Rating: AMBER; Mode of pathogenicity: ; Publications: 28804536, 24385928; Phenotypes: Mitochondrial complex III deficiency, nuclear type 7, OMIM:615824; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 TXN2 Stephanie Allen reviewed gene: TXN2: Rating: AMBER; Mode of pathogenicity: ; Publications: 26626369; Phenotypes: ?Combined oxidative phosphorylation deficiency 29 , OMIM:616811; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 TRMU Stephanie Allen reviewed gene: TRMU: Rating: RED; Mode of pathogenicity: ; Publications: 23625533; Phenotypes: Liver failure, transient infantile, OMIM:613070; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 TRIT1 Stephanie Allen reviewed gene: TRIT1: Rating: AMBER; Mode of pathogenicity: ; Publications: 32088416; Phenotypes: Combined oxidative phosphorylation deficiency 35, OMIM:617873; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 TMEM65 Stephanie Allen reviewed gene: TMEM65: Rating: AMBER; Mode of pathogenicity: ; Publications: 28295037; Phenotypes: TMEM65 related mitochondrial encephalopmyopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 TK2 Stephanie Allen reviewed gene: TK2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Mitochondrial DNA depletion syndrome 2 (myopathic type), OMIM:609560; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 SUCLA2 Stephanie Allen reviewed gene: SUCLA2: Rating: AMBER; Mode of pathogenicity: ; Publications: 17287286; Phenotypes: Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), OMIM:612073; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 SLC25A46 Stephanie Allen reviewed gene: SLC25A46: Rating: GREEN; Mode of pathogenicity: ; Publications: 28653766, 35012485, 27543974, 26951855; Phenotypes: Pontocerebellar hypoplasia, type 1E, OMIM:619303; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 SLC25A1 Stephanie Allen reviewed gene: SLC25A1: Rating: AMBER; Mode of pathogenicity: ; Publications: 23393310, 24687295, 25614306; Phenotypes: Combined D-2- and L-2-hydroxyglutaric aciduria, OMIM:615182; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 SFXN4 Stephanie Allen reviewed gene: SFXN4: Rating: AMBER; Mode of pathogenicity: ; Publications: 24119684; Phenotypes: Combined oxidative phosphorylation deficiency 18, OMIM:615578; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 SDHD Stephanie Allen reviewed gene: SDHD: Rating: RED; Mode of pathogenicity: ; Publications: 26008905; Phenotypes: Mitochondrial complex II deficiency, nuclear type 3, OMIM:619167; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 RMND1 Stephanie Allen reviewed gene: RMND1: Rating: GREEN; Mode of pathogenicity: ; Publications: 25604853, 27412952; Phenotypes: Combined oxidative phosphorylation deficiency 11, OMIM:614922; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 QRSL1 Stephanie Allen reviewed gene: QRSL1: Rating: GREEN; Mode of pathogenicity: ; Publications: 29440775, 30283131; Phenotypes: Combined oxidative phosphorylation deficiency 40, OMIM:618835; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 POLG Stephanie Allen reviewed gene: POLG: Rating: AMBER; Mode of pathogenicity: ; Publications: 29574624, 33579567, 8368248; Phenotypes: Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE), OMIM:607459, Mitochondrial DNA depletion syndrome 4A (Alpers type), OMIM:203700, Mitochondrial DNA depletion syndrome 4B (MNGIE type), OMIM:613662; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 PNPLA8 Stephanie Allen reviewed gene: PNPLA8: Rating: GREEN; Mode of pathogenicity: ; Publications: 29681094, 34177434; Phenotypes: ?Mitochondrial myopathy with lactic acidosis, OMIM:251950; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 PET100 Stephanie Allen reviewed gene: PET100: Rating: GREEN; Mode of pathogenicity: ; Publications: 25293719; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 12, OMIM:619055; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 PDHX Stephanie Allen reviewed gene: PDHX: Rating: GREEN; Mode of pathogenicity: ; Publications: 20002125, 34873726; Phenotypes: Lacticacidemia due to PDX1 deficiency, OMIM:245349; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 PDHB Stephanie Allen reviewed gene: PDHB: Rating: GREEN; Mode of pathogenicity: ; Publications: 26865159; Phenotypes: Pyruvate dehydrogenase E1-beta deficiency, OMIM:614111; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 PC Stephanie Allen reviewed gene: PC: Rating: GREEN; Mode of pathogenicity: ; Publications: 30870574, 29752808, 34485016, 10323732; Phenotypes: Pyruvate carboxylase deficiency, OMIM:266150; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 NDUFV2 Stephanie Allen reviewed gene: NDUFV2: Rating: AMBER; Mode of pathogenicity: ; Publications: 26008862; Phenotypes: Mitochondrial complex I deficiency, nuclear type 7, OMIM:618229; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 NDUFS1 Stephanie Allen reviewed gene: NDUFS1: Rating: GREEN; Mode of pathogenicity: ; Publications: 20382551, 31557978; Phenotypes: Mitochondrial complex I deficiency, nuclear type 5, OMIM:618226; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 NDUFC2 Stephanie Allen reviewed gene: NDUFC2: Rating: AMBER; Mode of pathogenicity: ; Publications: 32969598; Phenotypes: Mitochondrial complex I deficiency, nuclear type 36, OMIM:619170; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 NDUFB7 Stephanie Allen reviewed gene: NDUFB7: Rating: AMBER; Mode of pathogenicity: ; Publications: 33502047; Phenotypes: ?Mitochondrial complex I deficiency, nuclear type 39, OMIM:620135; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 NDUFB3 Stephanie Allen reviewed gene: NDUFB3: Rating: GREEN; Mode of pathogenicity: ; Publications: 27091925, 22277967; Phenotypes: Mitochondrial complex I deficiency, nuclear type 25, OMIM:618246; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 NDUFB11 Stephanie Allen reviewed gene: NDUFB11: Rating: GREEN; Mode of pathogenicity: ; Publications: 25772934; Phenotypes: ?Mitochondrial complex I deficiency, nuclear type 30, OMIM:301021, Linear skin defects with multiple congenital anomalies 3, OMIM:300952; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Fetal anomalies v3.8 NDUFB10 Stephanie Allen reviewed gene: NDUFB10: Rating: GREEN; Mode of pathogenicity: ; Publications: 31130284, 28040730; Phenotypes: Mitochondrial complex I deficiency, nuclear type 35, OMIM:619003; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 NDUFAF8 Stephanie Allen reviewed gene: NDUFAF8: Rating: GREEN; Mode of pathogenicity: ; Publications: 31866046; Phenotypes: Mitochondrial complex I deficiency, nuclear type 34, OMIM:618776; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 NDUFA6 Stephanie Allen reviewed gene: NDUFA6: Rating: GREEN; Mode of pathogenicity: ; Publications: 30245030; Phenotypes: Mitochondrial complex I deficiency, nuclear type 33, OMIM:618253; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 NDUFA12 Stephanie Allen reviewed gene: NDUFA12: Rating: RED; Mode of pathogenicity: ; Publications: 32341820, 35141356; Phenotypes: Mitochondrial complex I deficiency, nuclear type 23, OMIM:618244; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 NADK2 Stephanie Allen reviewed gene: NADK2: Rating: AMBER; Mode of pathogenicity: ; Publications: 27940755; Phenotypes: 2,4-dienoyl-CoA reductase deficiency, OMIM:616034; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 MTPAP Stephanie Allen reviewed gene: MTPAP: Rating: AMBER; Mode of pathogenicity: ; Publications: 31779033; Phenotypes: ?Spastic ataxia 4, autosomal recessive, OMIM:613672; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 MTFMT Stephanie Allen reviewed gene: MTFMT: Rating: GREEN; Mode of pathogenicity: ; Publications: 27393152, 30911575; Phenotypes: Combined oxidative phosphorylation deficiency 15, OMIM:614947, Mitochondrial complex I deficiency, nuclear type 27, OMIM:618248; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 MRPS14 Stephanie Allen reviewed gene: MRPS14: Rating: GREEN; Mode of pathogenicity: ; Publications: 30358850; Phenotypes: ?Combined oxidative phosphorylation deficiency 38, OMIM:618378; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 MPC2 Stephanie Allen reviewed gene: MPC2: Rating: AMBER; Mode of pathogenicity: ; Publications: 36417180; Phenotypes: Mitochondrial pyruvate carrier deficiency; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 MPC1 Stephanie Allen reviewed gene: MPC1: Rating: AMBER; Mode of pathogenicity: ; Publications: 34873722, 31145700; Phenotypes: Mitochondrial pyruvate carrier deficiency, OMIM:614741; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 IBA57 Stephanie Allen reviewed gene: IBA57: Rating: GREEN; Mode of pathogenicity: ; Publications: 23462291, 33890810; Phenotypes: Multiple mitochondrial dysfunctions syndrome 3, OMIM:615330; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 GFM2 Stephanie Allen reviewed gene: GFM2: Rating: AMBER; Mode of pathogenicity: ; Publications: 29075935, 26016410; Phenotypes: Combined oxidative phosphorylation deficiency 39, OMIM:618397; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 GATB Stephanie Allen reviewed gene: GATB: Rating: GREEN; Mode of pathogenicity: ; Publications: 30283131; Phenotypes: ?Combined oxidative phosphorylation deficiency 41, OMIM:618838; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 ECHS1 Stephanie Allen reviewed gene: ECHS1: Rating: GREEN; Mode of pathogenicity: ; Publications: 30918357, 26920905, 26000322; Phenotypes: Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency, OMIM:616277; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 EARS2 Stephanie Allen reviewed gene: EARS2: Rating: GREEN; Mode of pathogenicity: ; Publications: 27571996, 31680123; Phenotypes: Combined oxidative phosphorylation deficiency 12, OMIM:614924; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 DNA2 Stephanie Allen reviewed gene: DNA2: Rating: GREEN; Mode of pathogenicity: ; Publications: 31045292, 24389050; Phenotypes: Seckel syndrome 8, OMIM:615807; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 DGUOK Stephanie Allen reviewed gene: DGUOK: Rating: AMBER; Mode of pathogenicity: ; Publications: 22868686; Phenotypes: Mitochondrial DNA depletion syndrome 3 (hepatocerebral type), OMIM:251880, Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 4, OMIM:617070, Portal hypertension, noncirrhotic, 1, OMIM:617068; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 DARS2 Stephanie Allen reviewed gene: DARS2: Rating: GREEN; Mode of pathogenicity: ; Publications: 33977142; Phenotypes: Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, OMIM:611105; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 COX14 Stephanie Allen reviewed gene: COX14: Rating: AMBER; Mode of pathogenicity: ; Publications: 22243966; Phenotypes: ?Mitochondrial complex IV deficiency, nuclear type 10 , OMIM:619053; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 COQ7 Stephanie Allen reviewed gene: COQ7: Rating: GREEN; Mode of pathogenicity: ; Publications: 26084283, 31240163; Phenotypes: ?Coenzyme Q10 deficiency, primary, 8, OMIM:616733; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 COA6 Stephanie Allen reviewed gene: COA6: Rating: AMBER; Mode of pathogenicity: ; Publications: 22277967, 25339201; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 13, OMIM:616501; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 C1QBP Stephanie Allen reviewed gene: C1QBP: Rating: GREEN; Mode of pathogenicity: ; Publications: 33977026, 28942965; Phenotypes: Combined oxidative phosphorylation deficiency 33, OMIM:617713; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 C19orf70 Stephanie Allen reviewed gene: C19orf70: Rating: GREEN; Mode of pathogenicity: ; Publications: 27485409, 29618761; Phenotypes: Combined oxidative phosphorylation deficiency 37, OMIM:618329; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 ATP5O Stephanie Allen reviewed gene: ATP5O: Rating: GREEN; Mode of pathogenicity: ; Publications: 35621276; Phenotypes: Mitochondrial complex V (ATP synthase) deficiency; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 AARS2 Stephanie Allen reviewed gene: AARS2: Rating: GREEN; Mode of pathogenicity: ; Publications: 30819764, 28822227, 21549344; Phenotypes: Combined oxidative phosphorylation deficiency 8, OMIM:614096, Leukoencephalopathy, progressive, with ovarian failure, OMIM:615889; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.7 ZMYM2 Arina Puzriakova gene: ZMYM2 was added
gene: ZMYM2 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: ZMYM2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: ZMYM2 were set to Neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities, OMIM:619522
Fetal anomalies v3.7 LRIG2 Arina Puzriakova Added phenotypes Urofacial syndrome 2, OMIM:615112 for gene: LRIG2
Fetal anomalies v3.7 AGTR1 Arina Puzriakova gene: AGTR1 was added
gene: AGTR1 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: AGTR1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: AGTR1 were set to Renal tubular dysgenesis, OMIM:267430
Fetal anomalies v3.7 CLCN4 Arina Puzriakova gene: CLCN4 was added
gene: CLCN4 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: CLCN4 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: CLCN4 were set to Raynaud-Claes syndrome, OMIM:300114
Fetal anomalies v3.7 MECOM Arina Puzriakova Added phenotypes Radioulnar synostosis with amegakaryocytic thrombocytopenia 2, OMIM:616738 for gene: MECOM
Fetal anomalies v3.7 TK2 Arina Puzriakova Added phenotypes Mitochondrial DNA depletion syndrome 2 (myopathic type), OMIM:609560 for gene: TK2
Fetal anomalies v3.7 RMND1 Arina Puzriakova Added phenotypes Combined oxidative phosphorylation deficiency 11, OMIM:614922 for gene: RMND1
Fetal anomalies v3.7 PET100 Arina Puzriakova Added phenotypes Mitochondrial complex IV deficiency, nuclear type 12, OMIM:619055 for gene: PET100
Fetal anomalies v3.7 NDUFB10 Arina Puzriakova Added phenotypes Mitochondrial complex I deficiency, nuclear type 35, OMIM:619003 for gene: NDUFB10
Fetal anomalies v3.7 C1QBP Arina Puzriakova Added phenotypes Combined oxidative phosphorylation deficiency 33, OMIM:617713 for gene: C1QBP
Fetal anomalies v3.7 POLG Arina Puzriakova Source Expert Review Amber was added to POLG.
Added phenotypes Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE), OMIM:607459; Mitochondrial DNA depletion syndrome 4A (Alpers type), OMIM:203700; Mitochondrial DNA depletion syndrome 4B (MNGIE type), OMIM:613662 for gene: POLG
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Fetal anomalies v3.7 PDHX Arina Puzriakova Source Expert Review Amber was added to PDHX.
Added phenotypes Lacticacidemia due to PDX1 deficiency, OMIM:245349 for gene: PDHX
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)