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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.
Childhood onset dystonia, chorea or related movement disorder 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
Childhood onset dystonia, chorea or related movement disorder v3.13 TSPOAP1 Sarah Leigh Tag Q3_23_promote_green was removed from TSPOAP1.
Childhood onset dystonia, chorea or related movement disorder 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).
Childhood onset dystonia, chorea or related movement disorder 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).
Childhood onset dystonia, chorea or related movement disorder v3.12 TSPOAP1 Sarah Leigh Tag Q3_23_promote_green tag was added to gene: TSPOAP1.
Childhood onset dystonia, chorea or related movement disorder 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
Childhood onset dystonia, chorea or related movement disorder v3.12 TSPOAP1 Sarah Leigh Classified gene: TSPOAP1 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder 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.
Childhood onset dystonia, chorea or related movement disorder 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 with onset in adulthood 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
Adult onset hereditary spastic paraplegia 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
Adult onset hereditary spastic paraplegia v3.10 PRNP Sarah Leigh Publications for gene: PRNP were set to 30240140; 8250529; 34746379; 28195350; 16227536; 19228673; 1699173; 7902971; 11709001; 10581485; 10953183; 1363810
Adult onset hereditary spastic paraplegia v3.9 PRNP Sarah Leigh Publications for gene: PRNP were set to 30240140; 8250529; 34746379; 28195350; 16227536; 19228673; 1699173; 7902971; 11709001; 10581485; 10953183
Adult onset hereditary spastic paraplegia 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
Adult onset hereditary spastic paraplegia v3.7 PRNP Sarah Leigh Classified gene: PRNP as Amber List (moderate evidence)
Adult onset hereditary spastic paraplegia 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.
Adult onset hereditary spastic paraplegia v3.7 PRNP Sarah Leigh Gene: prnp has been classified as Amber List (Moderate Evidence).
Adult onset hereditary spastic paraplegia v3.6 PRNP Sarah Leigh Publications for gene: PRNP were set to 30240140; 8250529; 34746379; 28195350; 16227536; 19228673
Adult onset hereditary spastic paraplegia v3.5 PRNP Sarah Leigh Tag Q3_23_promote_green tag was added to gene: PRNP.
Adult onset hereditary spastic paraplegia 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.
Adult onset hereditary spastic paraplegia 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
Childhood onset hereditary spastic paraplegia v4.10 CCDC82 Achchuthan Shanmugasundram Classified gene: CCDC82 as Amber List (moderate evidence)
Childhood onset hereditary spastic paraplegia v4.10 CCDC82 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are two unrelated cases and hence this gene should be rated AMBER.
Childhood onset hereditary spastic paraplegia v4.10 CCDC82 Achchuthan Shanmugasundram Gene: ccdc82 has been classified as Amber List (Moderate Evidence).
Childhood onset hereditary spastic paraplegia 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
Childhood onset dystonia, chorea or related movement disorder 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
Childhood onset dystonia, chorea or related movement disorder v3.11 NUP54 Achchuthan Shanmugasundram Classified gene: NUP54 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder 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.
Childhood onset dystonia, chorea or related movement disorder v3.11 NUP54 Achchuthan Shanmugasundram Gene: nup54 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v3.10 NUP54 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: NUP54.
Childhood onset dystonia, chorea or related movement disorder 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.
Adult onset dystonia, chorea or related movement disorder 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 - narrow panel v3.14 CLDN5 Achchuthan Shanmugasundram Classified gene: CLDN5 as Amber List (moderate evidence)
White matter disorders and cerebral calcification - narrow panel 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 - narrow panel v3.14 CLDN5 Achchuthan Shanmugasundram Gene: cldn5 has been classified as Amber List (Moderate Evidence).
White matter disorders and cerebral calcification - narrow panel 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 - narrow panel v3.13 CLDN5 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: CLDN5.
White matter disorders and cerebral calcification - narrow panel v3.13 CLDN5 Achchuthan Shanmugasundram Phenotypes for gene: CLDN5 were changed from Brain calcifications to Brain calcifications
White matter disorders and cerebral calcification - narrow panel v3.12 CLDN5 Achchuthan Shanmugasundram Phenotypes for gene: CLDN5 were changed from Brain calcifications to Brain calcifications
White matter disorders and cerebral calcification - narrow panel v3.12 CLDN5 Achchuthan Shanmugasundram Phenotypes for gene: CLDN5 were changed from epilepsy, MONDO:0005027 to Brain calcifications
White matter disorders and cerebral calcification - narrow panel 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 - narrow panel 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 - narrow panel v4.13 FEM1C Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: FEM1C.
Ataxia and cerebellar anomalies - narrow panel v4.13 FEM1C Achchuthan Shanmugasundram Classified gene: FEM1C as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel 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 - narrow panel v4.13 FEM1C Achchuthan Shanmugasundram Gene: fem1c has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel 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 - narrow panel 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
Adult onset hereditary spastic paraplegia 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
Adult onset leukodystrophy v3.8 NPC1 Achchuthan Shanmugasundram Tag watchlist tag was added to gene: NPC1.
Adult onset neurodegenerative disorder v4.26 VRK1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: VRK1.
Adult onset neurodegenerative disorder v4.26 VRK1 Achchuthan Shanmugasundram Classified gene: VRK1 as Amber List (moderate evidence)
Adult onset neurodegenerative disorder 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.
Adult onset neurodegenerative disorder v4.26 VRK1 Achchuthan Shanmugasundram Gene: vrk1 has been classified as Amber List (Moderate Evidence).
Adult onset neurodegenerative disorder 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
Adult onset neurodegenerative disorder v4.24 VRK1 Achchuthan Shanmugasundram Publications for gene: VRK1 were set to 26583493
Adult onset neurodegenerative disorder 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
Adult onset leukodystrophy v3.8 NPC1 Achchuthan Shanmugasundram edited their review of gene: NPC1: Changed rating: AMBER
Adult onset leukodystrophy v3.8 NPC1 Achchuthan Shanmugasundram Classified gene: NPC1 as Amber List (moderate evidence)
Adult onset leukodystrophy 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.
Adult onset leukodystrophy 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).
Adult onset leukodystrophy v3.7 NPC1 Achchuthan Shanmugasundram Publications for gene: NPC1 were set to 26910362; 29406968
Adult onset leukodystrophy 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
Adult onset leukodystrophy v3.6 MAN2B1 Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: MAN2B1.
Adult onset leukodystrophy v3.6 MAN2B1 Achchuthan Shanmugasundram Classified gene: MAN2B1 as Red List (low evidence)
Adult onset leukodystrophy 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.
Adult onset leukodystrophy 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
Adult onset leukodystrophy v3.5 MAN2B1 Achchuthan Shanmugasundram Deleted their comment
Adult onset leukodystrophy 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
Adult onset leukodystrophy 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).
Adult onset leukodystrophy v3.5 MAN2B1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: MAN2B1.
Adult onset leukodystrophy v3.5 MAN2B1 Achchuthan Shanmugasundram Classified gene: MAN2B1 as Amber List (moderate evidence)
Adult onset leukodystrophy 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.
Adult onset leukodystrophy v3.5 MAN2B1 Achchuthan Shanmugasundram Gene: man2b1 has been classified as Amber List (Moderate Evidence).
Adult onset leukodystrophy 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
Adult onset leukodystrophy v3.3 MAN2B1 Achchuthan Shanmugasundram Publications for gene: MAN2B1 were set to
Adult onset leukodystrophy 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
Childhood onset dystonia, chorea or related movement disorder v3.9 COASY Sarah Leigh Publications for gene: COASY were set to 27021474; 24360804
Adult onset dystonia, chorea or related movement disorder v3.2 COASY Sarah Leigh Publications for gene: COASY were set to 24360804; 27021474
Hereditary ataxia with onset in adulthood 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
Adult onset neurodegenerative disorder 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 - narrow panel v4.11 INTS11 Arina Puzriakova Entity copied from Intellectual disability - microarray and sequencing v5.151
Ataxia and cerebellar anomalies - narrow panel 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 with onset in adulthood 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 with onset in adulthood 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 with onset in adulthood 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
Childhood onset dystonia, chorea or related movement disorder v3.8 ARFGEF3 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: ARFGEF3.
Childhood onset dystonia, chorea or related movement disorder v3.8 ARFGEF3 Achchuthan Shanmugasundram Classified gene: ARFGEF3 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder 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.
Childhood onset dystonia, chorea or related movement disorder v3.8 ARFGEF3 Achchuthan Shanmugasundram Gene: arfgef3 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v3.7 ARFGEF3 Achchuthan Shanmugasundram Phenotypes for gene: ARFGEF3 were changed from Dystonia to early-onset generalized dystonia, MONDO:0100016
Childhood onset dystonia, chorea or related movement disorder 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
Confirmed 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 with onset in adulthood 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 - narrow panel v3.10 ENTPD1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: ENTPD1.
White matter disorders and cerebral calcification - narrow panel v3.10 ENTPD1 Achchuthan Shanmugasundram Classified gene: ENTPD1 as Amber List (moderate evidence)
White matter disorders and cerebral calcification - narrow panel 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 - narrow panel v3.10 ENTPD1 Achchuthan Shanmugasundram Gene: entpd1 has been classified as Amber List (Moderate Evidence).
White matter disorders and cerebral calcification - narrow panel 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 - narrow panel 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 - narrow panel 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 - narrow panel 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 - narrow panel 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 - narrow panel 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).
Childhood onset hereditary spastic paraplegia v4.8 CHMP3 Arina Puzriakova Classified gene: CHMP3 as Red List (low evidence)
Childhood onset hereditary spastic paraplegia 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.
Childhood onset hereditary spastic paraplegia 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
Childhood onset hereditary spastic paraplegia 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 with onset in adulthood 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)
Fetal anomalies v3.7 PDHB Arina Puzriakova Source Expert Review Amber was added to PDHB.
Added phenotypes Pyruvate dehydrogenase E1-beta deficiency, OMIM:614111 for gene: PDHB
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Fetal anomalies v3.7 PC Arina Puzriakova Source Expert Review Amber was added to PC.
Added phenotypes Pyruvate carboxylase deficiency, OMIM:266150 for gene: PC
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Fetal anomalies v3.7 NDUFS1 Arina Puzriakova Source Expert Review Amber was added to NDUFS1.
Added phenotypes Mitochondrial complex I deficiency, nuclear type 5, OMIM:618226 for gene: NDUFS1
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Fetal anomalies v3.7 DARS2 Arina Puzriakova Source Expert Review Amber was added to DARS2.
Added phenotypes Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, OMIM:611105 for gene: DARS2
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Fetal anomalies v3.7 TRMU Arina Puzriakova gene: TRMU was added
gene: TRMU was added to Fetal anomalies. Sources: Expert Review Red
Mode of inheritance for gene: TRMU was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TRMU were set to Liver failure, transient infantile, OMIM:613070
Fetal anomalies v3.7 SDHD Arina Puzriakova gene: SDHD was added
gene: SDHD was added to Fetal anomalies. Sources: Expert Review Red
Mode of inheritance for gene: SDHD was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SDHD were set to Mitochondrial complex II deficiency, nuclear type 3, OMIM:619167
Fetal anomalies v3.7 NDUFA12 Arina Puzriakova gene: NDUFA12 was added
gene: NDUFA12 was added to Fetal anomalies. Sources: Expert Review Red
Mode of inheritance for gene: NDUFA12 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NDUFA12 were set to Mitochondrial complex I deficiency, nuclear type 23, OMIM:618244
Fetal anomalies v3.7 WARS2 Arina Puzriakova gene: WARS2 was added
gene: WARS2 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: WARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WARS2 were set to Neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures, OMIM:617710
Fetal anomalies v3.7 VARS2 Arina Puzriakova gene: VARS2 was added
gene: VARS2 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: VARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VARS2 were set to Combined oxidative phosphorylation deficiency 20, OMIM:615917
Fetal anomalies v3.7 UQCRFS1 Arina Puzriakova gene: UQCRFS1 was added
gene: UQCRFS1 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: UQCRFS1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: UQCRFS1 were set to Mitochondrial complex III deficiency, nuclear type 10, OMIM:618775
Fetal anomalies v3.7 UQCC2 Arina Puzriakova gene: UQCC2 was added
gene: UQCC2 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: UQCC2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: UQCC2 were set to Mitochondrial complex III deficiency, nuclear type 7, OMIM:615824
Fetal anomalies v3.7 TXN2 Arina Puzriakova gene: TXN2 was added
gene: TXN2 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: TXN2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TXN2 were set to ?Combined oxidative phosphorylation deficiency 29 , OMIM:616811
Fetal anomalies v3.7 TRIT1 Arina Puzriakova gene: TRIT1 was added
gene: TRIT1 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: TRIT1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TRIT1 were set to Combined oxidative phosphorylation deficiency 35, OMIM:617873
Fetal anomalies v3.7 TMEM65 Arina Puzriakova gene: TMEM65 was added
gene: TMEM65 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: TMEM65 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TMEM65 were set to TMEM65 related mitochondrial encephalopmyopathy
Fetal anomalies v3.7 SUCLA2 Arina Puzriakova gene: SUCLA2 was added
gene: SUCLA2 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: SUCLA2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SUCLA2 were set to Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), OMIM:612073
Fetal anomalies v3.7 SLC25A46 Arina Puzriakova gene: SLC25A46 was added
gene: SLC25A46 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: SLC25A46 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC25A46 were set to Pontocerebellar hypoplasia, type 1E, OMIM:619303
Fetal anomalies v3.7 SLC25A1 Arina Puzriakova gene: SLC25A1 was added
gene: SLC25A1 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: SLC25A1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC25A1 were set to Combined D-2- and L-2-hydroxyglutaric aciduria, OMIM:615182
Fetal anomalies v3.7 SFXN4 Arina Puzriakova gene: SFXN4 was added
gene: SFXN4 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: SFXN4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SFXN4 were set to Combined oxidative phosphorylation deficiency 18, OMIM:615578
Fetal anomalies v3.7 QRSL1 Arina Puzriakova gene: QRSL1 was added
gene: QRSL1 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: QRSL1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: QRSL1 were set to Combined oxidative phosphorylation deficiency 40, OMIM:618835
Fetal anomalies v3.7 PNPLA8 Arina Puzriakova gene: PNPLA8 was added
gene: PNPLA8 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: PNPLA8 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PNPLA8 were set to ?Mitochondrial myopathy with lactic acidosis, OMIM:251950
Fetal anomalies v3.7 NDUFV2 Arina Puzriakova gene: NDUFV2 was added
gene: NDUFV2 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: NDUFV2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NDUFV2 were set to Mitochondrial complex I deficiency, nuclear type 7, OMIM:618229
Fetal anomalies v3.7 NDUFC2 Arina Puzriakova gene: NDUFC2 was added
gene: NDUFC2 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: NDUFC2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NDUFC2 were set to Mitochondrial complex I deficiency, nuclear type 36, OMIM:619170
Fetal anomalies v3.7 NDUFB7 Arina Puzriakova gene: NDUFB7 was added
gene: NDUFB7 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: NDUFB7 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NDUFB7 were set to ?Mitochondrial complex I deficiency, nuclear type 39, OMIM:620135
Fetal anomalies v3.7 NDUFB3 Arina Puzriakova gene: NDUFB3 was added
gene: NDUFB3 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: NDUFB3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NDUFB3 were set to Mitochondrial complex I deficiency, nuclear type 25, OMIM:618246
Fetal anomalies v3.7 NDUFAF8 Arina Puzriakova gene: NDUFAF8 was added
gene: NDUFAF8 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: NDUFAF8 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NDUFAF8 were set to Mitochondrial complex I deficiency, nuclear type 34, OMIM:618776
Fetal anomalies v3.7 NDUFA6 Arina Puzriakova gene: NDUFA6 was added
gene: NDUFA6 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: NDUFA6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NDUFA6 were set to Mitochondrial complex I deficiency, nuclear type 33, OMIM:618253
Fetal anomalies v3.7 NADK2 Arina Puzriakova gene: NADK2 was added
gene: NADK2 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: NADK2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NADK2 were set to 2,4-dienoyl-CoA reductase deficiency, OMIM:616034
Fetal anomalies v3.7 MTPAP Arina Puzriakova gene: MTPAP was added
gene: MTPAP was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: MTPAP was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MTPAP were set to ?Spastic ataxia 4, autosomal recessive, OMIM:613672
Fetal anomalies v3.7 MTFMT Arina Puzriakova gene: MTFMT was added
gene: MTFMT was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: MTFMT was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MTFMT were set to Combined oxidative phosphorylation deficiency 15, OMIM:614947; Mitochondrial complex I deficiency, nuclear type 27, OMIM:618248
Fetal anomalies v3.7 MRPS14 Arina Puzriakova gene: MRPS14 was added
gene: MRPS14 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: MRPS14 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MRPS14 were set to ?Combined oxidative phosphorylation deficiency 38, OMIM:618378
Fetal anomalies v3.7 MPC2 Arina Puzriakova gene: MPC2 was added
gene: MPC2 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: MPC2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MPC2 were set to Mitochondrial pyruvate carrier deficiency
Fetal anomalies v3.7 MPC1 Arina Puzriakova gene: MPC1 was added
gene: MPC1 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: MPC1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MPC1 were set to Mitochondrial pyruvate carrier deficiency, OMIM:614741
Fetal anomalies v3.7 IBA57 Arina Puzriakova gene: IBA57 was added
gene: IBA57 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: IBA57 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IBA57 were set to Multiple mitochondrial dysfunctions syndrome 3, OMIM:615330
Fetal anomalies v3.7 GFM2 Arina Puzriakova gene: GFM2 was added
gene: GFM2 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: GFM2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GFM2 were set to Combined oxidative phosphorylation deficiency 39, OMIM:618397
Fetal anomalies v3.7 GATB Arina Puzriakova gene: GATB was added
gene: GATB was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: GATB was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GATB were set to ?Combined oxidative phosphorylation deficiency 41, OMIM:618838
Fetal anomalies v3.7 ECHS1 Arina Puzriakova gene: ECHS1 was added
gene: ECHS1 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: ECHS1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ECHS1 were set to Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency, OMIM:616277
Fetal anomalies v3.7 EARS2 Arina Puzriakova gene: EARS2 was added
gene: EARS2 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: EARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: EARS2 were set to Combined oxidative phosphorylation deficiency 12, OMIM:614924
Fetal anomalies v3.7 DNA2 Arina Puzriakova gene: DNA2 was added
gene: DNA2 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: DNA2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DNA2 were set to Seckel syndrome 8, OMIM:615807
Fetal anomalies v3.7 DGUOK Arina Puzriakova gene: DGUOK was added
gene: DGUOK was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: DGUOK was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DGUOK were set to 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
Fetal anomalies v3.7 COX14 Arina Puzriakova gene: COX14 was added
gene: COX14 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: COX14 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: COX14 were set to ?Mitochondrial complex IV deficiency, nuclear type 10 , OMIM:619053
Fetal anomalies v3.7 COQ7 Arina Puzriakova gene: COQ7 was added
gene: COQ7 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: COQ7 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: COQ7 were set to ?Coenzyme Q10 deficiency, primary, 8, OMIM:616733
Fetal anomalies v3.7 COA6 Arina Puzriakova gene: COA6 was added
gene: COA6 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: COA6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: COA6 were set to Mitochondrial complex IV deficiency, nuclear type 13, OMIM:616501
Fetal anomalies v3.7 C19orf70 Arina Puzriakova gene: C19orf70 was added
gene: C19orf70 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: C19orf70 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: C19orf70 were set to Combined oxidative phosphorylation deficiency 37, OMIM:618329
Fetal anomalies v3.7 ATP5O Arina Puzriakova gene: ATP5O was added
gene: ATP5O was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: ATP5O was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ATP5O were set to Mitochondrial complex V (ATP synthase) deficiency
Fetal anomalies v3.7 AARS2 Arina Puzriakova Source Expert Review Amber was added to AARS2.
Added phenotypes Combined oxidative phosphorylation deficiency 8, OMIM:614096; Leukoencephalopathy, progressive, with ovarian failure, OMIM:615889 for gene: AARS2
Rating Changed from No List (delete) to Amber List (moderate evidence)
Mosaic skin disorders - deep sequencing v2.1 EPHB4 Tom Cullup gene: EPHB4 was added
gene: EPHB4 was added to Mosaic skin disorders - deep sequencing. Sources: Expert list
Mode of inheritance for gene: EPHB4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EPHB4 were set to PMID: 30760892
Phenotypes for gene: EPHB4 were set to Capillary malformation-arteriovenous malformation 2 (MIM 618196); Lymphatic malformation 7 (MIM 617300)
Penetrance for gene: EPHB4 were set to unknown
Review for gene: EPHB4 was set to GREEN
Added comment: EPHB4 well documented as disease-associated gene; only a single mosaic case so far reported in the literature (PMID: 30760892), but considered likely to be underestimate by Prof Kinsler's team. Important differential for RASA1-like presentation (CM-AVM).
Sources: Expert list
Mosaic skin disorders - deep sequencing v2.1 NEK9 Tom Cullup gene: NEK9 was added
gene: NEK9 was added to Mosaic skin disorders - deep sequencing. Sources: Expert list
Mode of inheritance for gene: NEK9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NEK9 were set to PMID: 27153399; 34184242; 33481271
Phenotypes for gene: NEK9 were set to nevus comedonicus (NC) (MIM: 617025)
Penetrance for gene: NEK9 were set to unknown
Mode of pathogenicity for gene: NEK9 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: NEK9 was set to GREEN
Added comment: Sources: Expert list
Mosaic skin disorders - deep sequencing v2.1 TEK Tom Cullup reviewed gene: TEK: 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: PMID: 27519652; Phenotypes: Blue rubber bleb naevus, multiple cutaneous and mucosal venous malformations (VMCM); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mosaic skin disorders - deep sequencing v2.1 PIK3R1 Tom Cullup gene: PIK3R1 was added
gene: PIK3R1 was added to Mosaic skin disorders - deep sequencing. Sources: Expert list
Mode of inheritance for gene: PIK3R1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PIK3R1 were set to PMID: 34040190; 35964931
Phenotypes for gene: PIK3R1 were set to Vascular malformation and overgrowth
Penetrance for gene: PIK3R1 were set to unknown
Mode of pathogenicity for gene: PIK3R1 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: PIK3R1 was set to GREEN
Added comment: Sources: Expert list
Segmental overgrowth disorders - Deep sequencing v3.5 PIK3R1 Tom Cullup gene: PIK3R1 was added
gene: PIK3R1 was added to Segmental overgrowth disorders - Deep sequencing. Sources: Expert list
Mode of inheritance for gene: PIK3R1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PIK3R1 were set to PMID: 34040190; 35964931
Phenotypes for gene: PIK3R1 were set to Vascular malformation and overgrowth
Penetrance for gene: PIK3R1 were set to unknown
Mode of pathogenicity for gene: PIK3R1 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: PIK3R1 was set to GREEN
Added comment: Sources: Expert list
Early onset or syndromic epilepsy v4.28 UNC13B Achchuthan Shanmugasundram Phenotypes for gene: UNC13B were changed from partial epilepsy, MONDO:0005384 to partial epilepsy, MONDO:0005384
Early onset or syndromic epilepsy v4.28 UNC13B Achchuthan Shanmugasundram Phenotypes for gene: UNC13B were changed from Epilepsy to partial epilepsy, MONDO:0005384
Early onset or syndromic epilepsy v4.27 UNC13B Achchuthan Shanmugasundram Publications for gene: UNC13B were set to 33876820; 35380625
Early onset or syndromic epilepsy v4.27 UNC13B Achchuthan Shanmugasundram Publications for gene: UNC13B were set to 33876820; 35380625
Early onset or syndromic epilepsy v4.27 UNC13B Achchuthan Shanmugasundram Publications for gene: UNC13B were set to 33876820
Early onset or syndromic epilepsy v4.26 UNC13B Achchuthan Shanmugasundram Classified gene: UNC13B as Red List (low evidence)
Early onset or syndromic epilepsy v4.26 UNC13B Achchuthan Shanmugasundram Gene: unc13b has been classified as Red List (Low Evidence).
Early onset or syndromic epilepsy v4.26 UNC13B Achchuthan Shanmugasundram Classified gene: UNC13B as Red List (low evidence)
Early onset or syndromic epilepsy v4.26 UNC13B Achchuthan Shanmugasundram Gene: unc13b has been classified as Red List (Low Evidence).
Early onset or syndromic epilepsy v4.26 UNC13B Achchuthan Shanmugasundram Classified gene: UNC13B as Red List (low evidence)
Early onset or syndromic epilepsy v4.26 UNC13B Achchuthan Shanmugasundram Gene: unc13b has been classified as Red List (Low Evidence).
Early onset or syndromic epilepsy v4.25 UNC13B Achchuthan Shanmugasundram reviewed gene: UNC13B: Rating: RED; Mode of pathogenicity: None; Publications: 33876820, 35380625; Phenotypes: partial epilepsy, MONDO:0005384; Mode of inheritance: None
Intellectual disability v5.107 SLC32A1 Achchuthan Shanmugasundram Classified gene: SLC32A1 as Amber List (moderate evidence)
Intellectual disability v5.107 SLC32A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (four unrelated cases and supporting functional studies) for this gene to be promoted to GREEN at the next GMS update.
Intellectual disability v5.107 SLC32A1 Achchuthan Shanmugasundram Gene: slc32a1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.107 SLC32A1 Achchuthan Shanmugasundram Classified gene: SLC32A1 as Amber List (moderate evidence)
Intellectual disability v5.107 SLC32A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (four unrelated cases and supporting functional studies) for this gene to be promoted to GREEN at the next GMS update.
Intellectual disability v5.107 SLC32A1 Achchuthan Shanmugasundram Gene: slc32a1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.107 SLC32A1 Achchuthan Shanmugasundram Classified gene: SLC32A1 as Amber List (moderate evidence)
Intellectual disability v5.107 SLC32A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (four unrelated cases and supporting functional studies) for this gene to be promoted to GREEN at the next GMS update.
Intellectual disability v5.107 SLC32A1 Achchuthan Shanmugasundram Gene: slc32a1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.106 SLC32A1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.106 SLC32A1 Achchuthan Shanmugasundram Classified gene: SLC32A1 as Amber List (moderate evidence)
Intellectual disability v5.106 SLC32A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (four unrelated cases and supporting functional studies) for this gene to be promoted to GREEN at the next GMS update.
Intellectual disability v5.106 SLC32A1 Achchuthan Shanmugasundram Gene: slc32a1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.106 SLC32A1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.106 SLC32A1 Achchuthan Shanmugasundram Classified gene: SLC32A1 as Amber List (moderate evidence)
Intellectual disability v5.106 SLC32A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (four unrelated cases and supporting functional studies) for this gene to be promoted to GREEN at the next GMS update.
Intellectual disability v5.106 SLC32A1 Achchuthan Shanmugasundram Gene: slc32a1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.106 SLC32A1 Achchuthan Shanmugasundram Classified gene: SLC32A1 as Amber List (moderate evidence)
Intellectual disability v5.106 SLC32A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (four unrelated cases and supporting functional studies) for this gene to be promoted to GREEN at the next GMS update.
Intellectual disability v5.106 SLC32A1 Achchuthan Shanmugasundram Gene: slc32a1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.105 SLC32A1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: SLC32A1.
Intellectual disability v5.105 SLC32A1 Achchuthan Shanmugasundram changed review comment from: PMID:36073542 reported four unrelated patients with four different de novo missense variants in SLC32A1 gene reported with global developmental delay, moderate-to-severe intellectual disability, infantile-onset epilepsy within the first 18 months of life, and a choreiform, dystonic, or dyskinetic movement disorder.

In silico modeling and functional analyses showed that these variants can impair GABAergic neurotransmission through at least two mechanisms, by affecting synaptic vesicle filling and by altering synaptic short-term plasticity.
Sources: Literature; to: PMID:36073542 reported four unrelated patients with four different de novo missense variants in SLC32A1 gene reported with global developmental delay, moderate-to-severe intellectual disability, infantile-onset epilepsy within the first 18 months of life, and a choreiform, dystonic, or dyskinetic movement disorder.

In silico modeling and functional analyses showed that these variants can impair GABAergic neurotransmission through at least two mechanisms, by affecting synaptic vesicle filling and by altering synaptic short-term plasticity.

Although this gene has not yet been associated with phenotypes in OMIM, it has been added to Gene2Phenotype with 'moderate' rating in the DD panel.

Sources: Literature
Intellectual disability v5.105 SLC32A1 Achchuthan Shanmugasundram gene: SLC32A1 was added
gene: SLC32A1 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: SLC32A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC32A1 were set to 36073542
Phenotypes for gene: SLC32A1 were set to developmental and epileptic encephalopathy, MONDO:0100062
Review for gene: SLC32A1 was set to GREEN
Added comment: PMID:36073542 reported four unrelated patients with four different de novo missense variants in SLC32A1 gene reported with global developmental delay, moderate-to-severe intellectual disability, infantile-onset epilepsy within the first 18 months of life, and a choreiform, dystonic, or dyskinetic movement disorder.

In silico modeling and functional analyses showed that these variants can impair GABAergic neurotransmission through at least two mechanisms, by affecting synaptic vesicle filling and by altering synaptic short-term plasticity.
Sources: Literature
Early onset or syndromic epilepsy v4.25 SLC32A1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Helen Lord (Oxford Medical Genetics Laboratories) and Zornitza Stark (Australian Genomics), there are 8 unrelated cases with genetic epilepsy with febrile seizures plus and 4 unrelated cases with a neurodevelopmental disorder comprising intellectual disability and infantile-onset epilepsy and there are supporting functional evidence. Hence, this gene can be promoted to GREEN at the next GMS update.; to: Comment on list classification: As reviewed by Helen Lord (Oxford Medical Genetics Laboratories) and Zornitza Stark (Australian Genomics), there are 8 unrelated cases with genetic epilepsy with febrile seizures plus and 4 unrelated cases with a neurodevelopmental disorder comprising intellectual disability and infantile-onset epilepsy and there are supporting functional evidence. Hence, this gene can be promoted to GREEN at the next GMS update.

Although this gene has not yet been associated with phenotypes in OMIM, it has been added to Gene2Phenotype with 'moderate' rating in the DD panel.
Early onset or syndromic epilepsy v4.25 SLC32A1 Achchuthan Shanmugasundram Deleted their comment
Early onset or syndromic epilepsy v4.25 SLC32A1 Achchuthan Shanmugasundram Deleted their comment
Early onset or syndromic epilepsy v4.25 SLC32A1 Achchuthan Shanmugasundram Classified gene: SLC32A1 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.25 SLC32A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Helen Lord (Oxford Medical Genetics Laboratories) and Zornitza Stark (Australian Genomics), there are 8 unrelated cases with genetic epilepsy with febrile seizures plus and 4 unrelated cases with a neurodevelopmental disorder comprising intellectual disability and infantile-onset epilepsy and there are supporting functional evidence. Hence, this gene can be promoted to GREEN at the next GMS update.
Early onset or syndromic epilepsy v4.25 SLC32A1 Achchuthan Shanmugasundram Gene: slc32a1 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.25 SLC32A1 Achchuthan Shanmugasundram Classified gene: SLC32A1 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.25 SLC32A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Helen Lord (Oxford Medical Genetics Laboratories) and Zornitza Stark (Australian Genomics), there are 8 unrelated cases with genetic epilepsy with febrile seizures plus and 4 unrelated cases with a neurodevelopmental disorder comprising intellectual disability and infantile-onset epilepsy and there are supporting functional evidence. Hence, this gene can be promoted to GREEN at the next GMS update.
Early onset or syndromic epilepsy v4.25 SLC32A1 Achchuthan Shanmugasundram Gene: slc32a1 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.25 SLC32A1 Achchuthan Shanmugasundram Classified gene: SLC32A1 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.25 SLC32A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Helen Lord (Oxford Medical Genetics Laboratories) and Zornitza Stark (Australian Genomics), there are 8 unrelated cases with genetic epilepsy with febrile seizures plus and 4 unrelated cases with a neurodevelopmental disorder comprising intellectual disability and infantile-onset epilepsy and there are supporting functional evidence. Hence, this gene can be promoted to GREEN at the next GMS update.
Early onset or syndromic epilepsy v4.25 SLC32A1 Achchuthan Shanmugasundram Gene: slc32a1 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.24 SLC32A1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: SLC32A1.
Early onset or syndromic epilepsy v4.24 SLC32A1 Achchuthan Shanmugasundram Phenotypes for gene: SLC32A1 were changed from developmental and epileptic encephalopathy, MONDO:0100062; generalized epilepsy with febrile seizures plus, MONDO:0018214 to developmental and epileptic encephalopathy, MONDO:0100062; generalized epilepsy with febrile seizures plus, MONDO:0018214
Early onset or syndromic epilepsy v4.24 SLC32A1 Achchuthan Shanmugasundram Phenotypes for gene: SLC32A1 were changed from developmental and epileptic encephalopathy, MONDO:0100062; generalized epilepsy with febrile seizures plus, MONDO:0018214 to developmental and epileptic encephalopathy, MONDO:0100062; generalized epilepsy with febrile seizures plus, MONDO:0018214
Early onset or syndromic epilepsy v4.24 SLC32A1 Achchuthan Shanmugasundram Phenotypes for gene: SLC32A1 were changed from Genetic epilepsy with febrile seizures plus to developmental and epileptic encephalopathy, MONDO:0100062; generalized epilepsy with febrile seizures plus, MONDO:0018214
Early onset or syndromic epilepsy v4.23 SLC32A1 Achchuthan Shanmugasundram Publications for gene: SLC32A1 were set to 34038384; 36073542
Early onset or syndromic epilepsy v4.23 SLC32A1 Achchuthan Shanmugasundram Publications for gene: SLC32A1 were set to 34038384
Early onset or syndromic epilepsy v4.22 SLC32A1 Achchuthan Shanmugasundram reviewed gene: SLC32A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34038384, 36073542; Phenotypes: developmental and epileptic encephalopathy, MONDO:0100062, generalized epilepsy with febrile seizures plus, MONDO:0018214; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.104 CSTF2 Achchuthan Shanmugasundram Phenotypes for gene: CSTF2 were changed from Intellectual disability, MONDO:0001071 to Intellectual disability, MONDO:0001071
Intellectual disability v5.104 CSTF2 Achchuthan Shanmugasundram Phenotypes for gene: CSTF2 were changed from Intellectual disability, MONDO:0001071 to Intellectual disability, MONDO:0001071
Intellectual disability v5.103 CSTF2 Achchuthan Shanmugasundram Phenotypes for gene: CSTF2 were changed from Intellectual disability, MONDO:0001071 to Intellectual disability, MONDO:0001071
Intellectual disability v5.104 CSTF2 Achchuthan Shanmugasundram Phenotypes for gene: CSTF2 were changed from Intellectual disability, MONDO:0001071 to Intellectual disability, MONDO:0001071
Intellectual disability v5.104 CSTF2 Achchuthan Shanmugasundram Phenotypes for gene: CSTF2 were changed from Intellectual disability, MONDO:0001071 to Intellectual disability, MONDO:0001071
Intellectual disability v5.103 CSTF2 Achchuthan Shanmugasundram Phenotypes for gene: CSTF2 were changed from Intellectual disability, MONDO:0001071 to Intellectual disability, MONDO:0001071
Intellectual disability v5.103 CSTF2 Achchuthan Shanmugasundram Phenotypes for gene: CSTF2 were changed from Intellectual disability, MONDO:0001071 to Intellectual disability, MONDO:0001071
Intellectual disability v5.103 CSTF2 Achchuthan Shanmugasundram Phenotypes for gene: CSTF2 were changed from Intellectual disability, MONDO:0001071 to Intellectual disability, MONDO:0001071
Intellectual disability v5.103 CSTF2 Achchuthan Shanmugasundram Phenotypes for gene: CSTF2 were changed from to Intellectual disability, MONDO:0001071
Intellectual disability v5.102 CSTF2 Achchuthan Shanmugasundram Publications for gene: CSTF2 were set to 26350204; 32816001
Intellectual disability v5.102 CSTF2 Achchuthan Shanmugasundram Publications for gene: CSTF2 were set to 26350204; 32816001
Intellectual disability v5.102 CSTF2 Achchuthan Shanmugasundram Publications for gene: CSTF2 were set to 26350204; 32816001
Intellectual disability v5.102 CSTF2 Achchuthan Shanmugasundram Publications for gene: CSTF2 were set to 26350204; 32816001
Intellectual disability v5.102 CSTF2 Achchuthan Shanmugasundram Publications for gene: CSTF2 were set to 26350204; 32816001
Intellectual disability v5.102 CSTF2 Achchuthan Shanmugasundram Publications for gene: CSTF2 were set to 26350204; 32816001
Intellectual disability v5.102 CSTF2 Achchuthan Shanmugasundram Publications for gene: CSTF2 were set to 26350204
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Mode of inheritance for gene: CSTF2 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 v5.101 CSTF2 Achchuthan Shanmugasundram Mode of inheritance for gene: CSTF2 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 v5.101 CSTF2 Achchuthan Shanmugasundram Mode of inheritance for gene: CSTF2 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 v5.101 CSTF2 Achchuthan Shanmugasundram Mode of inheritance for gene: CSTF2 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 v5.100 CSTF2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Mode of inheritance for gene: CSTF2 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 v5.100 CSTF2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Classified gene: CSTF2 as Amber List (moderate evidence)
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark (Australian Genomics), there is one family with intellectual disability, supported by functional studies. This gene should therefore be promoted to AMBER in this panel.
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Gene: cstf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Mode of inheritance for gene: CSTF2 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 v5.101 CSTF2 Achchuthan Shanmugasundram Mode of inheritance for gene: CSTF2 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 v5.100 CSTF2 Achchuthan Shanmugasundram Classified gene: CSTF2 as Amber List (moderate evidence)
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark (Australian Genomics), there is one family with intellectual disability, supported by functional studies. This gene should therefore be promoted to AMBER in this panel.
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Gene: cstf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Classified gene: CSTF2 as Amber List (moderate evidence)
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark (Australian Genomics), there is one family with intellectual disability, supported by functional studies. This gene should therefore be promoted to AMBER in this panel.
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Gene: cstf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Mode of inheritance for gene: CSTF2 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 v5.99 CSTF2 Achchuthan Shanmugasundram Classified gene: CSTF2 as Amber List (moderate evidence)
Intellectual disability v5.99 CSTF2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark (Australian Genomics), there is one family with intellectual disability, supported by functional studies. This gene should therefore be promoted to AMBER in this panel.
Intellectual disability v5.99 CSTF2 Achchuthan Shanmugasundram Gene: cstf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.99 CSTF2 Achchuthan Shanmugasundram Classified gene: CSTF2 as Amber List (moderate evidence)
Intellectual disability v5.99 CSTF2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark (Australian Genomics), there is one family with intellectual disability, supported by functional studies. This gene should therefore be promoted to AMBER in this panel.
Intellectual disability v5.99 CSTF2 Achchuthan Shanmugasundram Gene: cstf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.99 CSTF2 Achchuthan Shanmugasundram Classified gene: CSTF2 as Amber List (moderate evidence)
Intellectual disability v5.99 CSTF2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark (Australian Genomics), there is one family with intellectual disability, supported by functional studies. This gene should therefore be promoted to AMBER in this panel.
Intellectual disability v5.99 CSTF2 Achchuthan Shanmugasundram Gene: cstf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.98 CSTF2 Achchuthan Shanmugasundram reviewed gene: CSTF2: Rating: AMBER; Mode of pathogenicity: None; Publications: 32816001; Phenotypes: Intellectual disability, MONDO:0001071; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.98 HIST1H4E Ronnie Wright reviewed gene: HIST1H4E: Rating: GREEN; Mode of pathogenicity: Other; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability v5.98 SRRM2 Alistair Pagnamenta reviewed gene: SRRM2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35567594, 33057194; Phenotypes: Intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.98 PRKAR1B Achchuthan Shanmugasundram Classified gene: PRKAR1B as Amber List (moderate evidence)
Intellectual disability v5.98 PRKAR1B 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 update.
Intellectual disability v5.98 PRKAR1B Achchuthan Shanmugasundram Gene: prkar1b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.98 PRKAR1B Achchuthan Shanmugasundram Classified gene: PRKAR1B as Amber List (moderate evidence)
Intellectual disability v5.98 PRKAR1B 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 update.
Intellectual disability v5.98 PRKAR1B Achchuthan Shanmugasundram Gene: prkar1b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.98 PRKAR1B Achchuthan Shanmugasundram Classified gene: PRKAR1B as Amber List (moderate evidence)
Intellectual disability v5.98 PRKAR1B 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 update.
Intellectual disability v5.98 PRKAR1B Achchuthan Shanmugasundram Gene: prkar1b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.97 PRKAR1B Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.97 PRKAR1B Achchuthan Shanmugasundram Classified gene: PRKAR1B as Amber List (moderate evidence)
Intellectual disability v5.97 PRKAR1B 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 update.
Intellectual disability v5.97 PRKAR1B Achchuthan Shanmugasundram Gene: prkar1b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.97 PRKAR1B Achchuthan Shanmugasundram Classified gene: PRKAR1B as Amber List (moderate evidence)
Intellectual disability v5.97 PRKAR1B 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 update.
Intellectual disability v5.97 PRKAR1B Achchuthan Shanmugasundram Gene: prkar1b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.96 PRKAR1B Achchuthan Shanmugasundram Publications for gene: PRKAR1B were set to 25414040; 33833410
Intellectual disability v5.96 PRKAR1B Achchuthan Shanmugasundram Phenotypes for gene: PRKAR1B were changed from Marbach-Schaaf neurodevelopmental syndrome, OMIM:619680 to Global developmental delay; Intellectual disability; Autism; Attention deficit hyperactivity disorder; Aggressive behavior; Abnormality of movement; Upslanted palpebral fissure
Intellectual disability v5.96 PRKAR1B Achchuthan Shanmugasundram Publications for gene: PRKAR1B were set to 25414040; 33833410
Intellectual disability v5.96 PRKAR1B Achchuthan Shanmugasundram Publications for gene: PRKAR1B were set to 25414040; 33833410
Intellectual disability v5.97 PRKAR1B Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: PRKAR1B.
Intellectual disability v5.97 PRKAR1B Achchuthan Shanmugasundram Phenotypes for gene: PRKAR1B were changed from Marbach-Schaaf neurodevelopmental syndrome, OMIM:619680 to Marbach-Schaaf neurodevelopmental syndrome, OMIM:619680
Intellectual disability v5.96 PRKAR1B Achchuthan Shanmugasundram Phenotypes for gene: PRKAR1B were changed from Marbach-Schaaf neurodevelopmental syndrome, OMIM:619680 to Marbach-Schaaf neurodevelopmental syndrome, OMIM:619680
Intellectual disability v5.96 PRKAR1B Achchuthan Shanmugasundram Phenotypes for gene: PRKAR1B were changed from Global developmental delay; Intellectual disability; Autism; Attention deficit hyperactivity disorder; Aggressive behavior; Abnormality of movement; Upslanted palpebral fissure to Marbach-Schaaf neurodevelopmental syndrome, OMIM:619680
Intellectual disability v5.95 PRKAR1B Achchuthan Shanmugasundram Publications for gene: PRKAR1B were set to 25414040; 33833410
Intellectual disability v5.95 PRKAR1B Achchuthan Shanmugasundram Publications for gene: PRKAR1B were set to 25414040; 33833410
Intellectual disability v5.96 PRKAR1B Achchuthan Shanmugasundram Publications for gene: PRKAR1B were set to 25414040; 33833410
Intellectual disability v5.95 PRKAR1B Achchuthan Shanmugasundram Publications for gene: PRKAR1B were set to 25414040; 33833410
Intellectual disability v5.95 PRKAR1B Achchuthan Shanmugasundram Publications for gene: PRKAR1B were set to 25414040; 33833410
Intellectual disability v5.95 PRKAR1B Achchuthan Shanmugasundram Publications for gene: PRKAR1B were set to https://doi.org/10.1101/2020.09.10.20190314; 25414040
Intellectual disability v5.94 PRKAR1B Achchuthan Shanmugasundram Mode of inheritance for gene: PRKAR1B was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.94 PRKAR1B Achchuthan Shanmugasundram Mode of inheritance for gene: PRKAR1B was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.94 PRKAR1B Achchuthan Shanmugasundram Mode of inheritance for gene: PRKAR1B was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.94 PRKAR1B Achchuthan Shanmugasundram Mode of inheritance for gene: PRKAR1B was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.94 PRKAR1B Achchuthan Shanmugasundram Mode of inheritance for gene: PRKAR1B was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.93 PRKAR1B Achchuthan Shanmugasundram reviewed gene: PRKAR1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 33833410; Phenotypes: Marbach-Schaaf neurodevelopmental syndrome, OMIM:619680; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v4.22 PPFIBP1 Achchuthan Shanmugasundram Classified gene: PPFIBP1 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.22 PPFIBP1 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 update.
Early onset or syndromic epilepsy v4.22 PPFIBP1 Achchuthan Shanmugasundram Gene: ppfibp1 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.21 PPFIBP1 Achchuthan Shanmugasundram Phenotypes for gene: PPFIBP1 were changed from Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024 to Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024
Early onset or syndromic epilepsy v4.21 PPFIBP1 Achchuthan Shanmugasundram Phenotypes for gene: PPFIBP1 were changed from Global developmental delay; Intellectual disability; Microcephaly; Seizures; Abnormality of brain morphology; Abnormality of the cerebral white matter; Cerebral calcification; Abnormal cortical gyration; Hypertonia; Spastic tetraplegia; Generalized hypotonia; Small for gestational age; Growth delay; Failure to thrive; Feeding difficulties; abnormal heart morphology; Hearing abnormality; Cryptorchidism; Abnormality of vision to Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024
Early onset or syndromic epilepsy v4.20 PPFIBP1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: PPFIBP1.
Early onset or syndromic epilepsy v4.20 PPFIBP1 Achchuthan Shanmugasundram reviewed gene: PPFIBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35830857; Phenotypes: Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.93 PPFIBP1 Achchuthan Shanmugasundram changed review comment from: As reviewed by Konstantinos Varvagiannis, all individuals reported in PMID:35830857 (16 individuals from 12 families) shared a core phenotype of global developmental delay/intellectual disability (GDD/ID) and epilepsy. 15 were affected by profound or severe GDD/ID (15/16). They had not acquired speech (15/16) and showed impaired motor development (15/16).

This gene has already been associated with relevant phenotypes in both OMIM (MIM #620024) and Gene2Phenotype (with 'strong' rating in the DD panel).; to: As reviewed by Konstantinos Varvagiannis, all individuals (16 individuals from 12 families) reported in PMID:35830857 shared a core phenotype of global developmental delay/intellectual disability (GDD/ID) and epilepsy. 15 were affected by profound or severe GDD/ID (15/16). They had not acquired speech (15/16) and showed impaired motor development (15/16).

This gene has already been associated with relevant phenotypes in both OMIM (MIM #620024) and Gene2Phenotype (with 'strong' rating in the DD panel).
Intellectual disability v5.93 PPFIBP1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.93 PPFIBP1 Achchuthan Shanmugasundram changed review comment from: As reviewed by Konstantinos Varvagiannis, all individuals reported in PMID:35830857 shared a core phenotype of global developmental delay/intellectual disability (GDD/ID) and epilepsy. 15 were affected by profound or severe GDD/ID (15/16). They had not acquired speech (15/16) and showed impaired motor development (15/16).

This gene has already been associated with relevant phenotypes in both OMIM (MIM #620024) and Gene2Phenotype (with 'strong' rating in the DD panel).; to: As reviewed by Konstantinos Varvagiannis, all individuals reported in PMID:35830857 (16 individuals from 12 families) shared a core phenotype of global developmental delay/intellectual disability (GDD/ID) and epilepsy. 15 were affected by profound or severe GDD/ID (15/16). They had not acquired speech (15/16) and showed impaired motor development (15/16).

This gene has already been associated with relevant phenotypes in both OMIM (MIM #620024) and Gene2Phenotype (with 'strong' rating in the DD panel).
Intellectual disability v5.93 PPFIBP1 Achchuthan Shanmugasundram Classified gene: PPFIBP1 as Amber List (moderate evidence)
Intellectual disability v5.93 PPFIBP1 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 update.
Intellectual disability v5.93 PPFIBP1 Achchuthan Shanmugasundram Gene: ppfibp1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.93 PPFIBP1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.93 PPFIBP1 Achchuthan Shanmugasundram Classified gene: PPFIBP1 as Amber List (moderate evidence)
Intellectual disability v5.93 PPFIBP1 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 update.
Intellectual disability v5.93 PPFIBP1 Achchuthan Shanmugasundram Gene: ppfibp1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.93 PPFIBP1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.93 PPFIBP1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.93 PPFIBP1 Achchuthan Shanmugasundram Classified gene: PPFIBP1 as Amber List (moderate evidence)
Intellectual disability v5.93 PPFIBP1 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 update.
Intellectual disability v5.93 PPFIBP1 Achchuthan Shanmugasundram Gene: ppfibp1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.92 PPFIBP1 Achchuthan Shanmugasundram Classified gene: PPFIBP1 as Amber List (moderate evidence)
Intellectual disability v5.92 PPFIBP1 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 update.
Intellectual disability v5.92 PPFIBP1 Achchuthan Shanmugasundram Gene: ppfibp1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.92 PPFIBP1 Achchuthan Shanmugasundram Classified gene: PPFIBP1 as Amber List (moderate evidence)
Intellectual disability v5.92 PPFIBP1 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 update.
Intellectual disability v5.92 PPFIBP1 Achchuthan Shanmugasundram Gene: ppfibp1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.91 PPFIBP1 Achchuthan Shanmugasundram Phenotypes for gene: PPFIBP1 were changed from Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024 to Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024
Intellectual disability v5.92 PPFIBP1 Achchuthan Shanmugasundram Phenotypes for gene: PPFIBP1 were changed from Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024 to Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024
Intellectual disability v5.91 PPFIBP1 Achchuthan Shanmugasundram Phenotypes for gene: PPFIBP1 were changed from Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024 to Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024
Intellectual disability v5.91 PPFIBP1 Achchuthan Shanmugasundram Phenotypes for gene: PPFIBP1 were changed from Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024 to Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024
Intellectual disability v5.92 PPFIBP1 Achchuthan Shanmugasundram Phenotypes for gene: PPFIBP1 were changed from Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024 to Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024
Intellectual disability v5.91 PPFIBP1 Achchuthan Shanmugasundram Phenotypes for gene: PPFIBP1 were changed from Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024 to Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024
Intellectual disability v5.91 PPFIBP1 Achchuthan Shanmugasundram Phenotypes for gene: PPFIBP1 were changed from Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024 to Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024
Intellectual disability v5.92 PPFIBP1 Achchuthan Shanmugasundram Phenotypes for gene: PPFIBP1 were changed from Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024 to Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024
Intellectual disability v5.91 PPFIBP1 Achchuthan Shanmugasundram Phenotypes for gene: PPFIBP1 were changed from Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024 to Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024
Intellectual disability v5.91 PPFIBP1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: PPFIBP1.
Intellectual disability v5.91 PPFIBP1 Achchuthan Shanmugasundram Phenotypes for gene: PPFIBP1 were changed from Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024 to Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024
Intellectual disability v5.91 PPFIBP1 Achchuthan Shanmugasundram Phenotypes for gene: PPFIBP1 were changed from Global developmental delay; Intellectual disability; Microcephaly; Seizures; Abnormality of brain morphology; Abnormality of the cerebral white matter; Cerebral calcification; Abnormal cortical gyration; Hypertonia; Spastic tetraplegia; Generalized hypotonia; Small for gestational age; Growth delay; Failure to thrive; Feeding difficulties; abnormal heart morphology; Hearing abnormality; Cryptorchidism; Abnormality of vision to Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024
Intellectual disability v5.90 PPFIBP1 Achchuthan Shanmugasundram changed review comment from: As reviewed by Konstantinos Varvagiannis, all individuals reported in PMID:35830857 shared a core phenotype of global developmental delay/intellectual disability (GDD/ID) and epilepsy. 15 were affected by profound or severe GDD/ID (15/16). They had not acquired speech (15/16) and showed impaired motor development (15/16).; to: As reviewed by Konstantinos Varvagiannis, all individuals reported in PMID:35830857 shared a core phenotype of global developmental delay/intellectual disability (GDD/ID) and epilepsy. 15 were affected by profound or severe GDD/ID (15/16). They had not acquired speech (15/16) and showed impaired motor development (15/16).

This gene has already been associated with relevant phenotypes in both OMIM (MIM #620024) and Gene2Phenotype (with 'strong' rating in the DD panel).
Intellectual disability v5.90 PPFIBP1 Achchuthan Shanmugasundram edited their review of gene: PPFIBP1: Changed phenotypes to: Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024
Intellectual disability v5.90 PPFIBP1 Achchuthan Shanmugasundram reviewed gene: PPFIBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35830857; Phenotypes: intellectual disability, MONDO:0001071; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.90 KDM2B Achchuthan Shanmugasundram Classified gene: KDM2B as Amber List (moderate evidence)
Intellectual disability v5.90 KDM2B 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 update.
Intellectual disability v5.90 KDM2B Achchuthan Shanmugasundram Gene: kdm2b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.89 KDM2B Achchuthan Shanmugasundram Classified gene: KDM2B as Amber List (moderate evidence)
Intellectual disability v5.89 KDM2B 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 update.
Intellectual disability v5.89 KDM2B Achchuthan Shanmugasundram Gene: kdm2b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.89 KDM2B Achchuthan Shanmugasundram Classified gene: KDM2B as Amber List (moderate evidence)
Intellectual disability v5.89 KDM2B 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 update.
Intellectual disability v5.89 KDM2B Achchuthan Shanmugasundram Gene: kdm2b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.89 KDM2B Achchuthan Shanmugasundram Classified gene: KDM2B as Amber List (moderate evidence)
Intellectual disability v5.89 KDM2B 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 update.
Intellectual disability v5.89 KDM2B Achchuthan Shanmugasundram Gene: kdm2b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.88 KDM2B Achchuthan Shanmugasundram Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.88 KDM2B Achchuthan Shanmugasundram Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.88 KDM2B Achchuthan Shanmugasundram Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.87 KDM2B Achchuthan Shanmugasundram Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.87 KDM2B Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: KDM2B.
Intellectual disability v5.87 KDM2B Achchuthan Shanmugasundram Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.88 KDM2B Achchuthan Shanmugasundram Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.88 KDM2B Achchuthan Shanmugasundram Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.87 KDM2B Achchuthan Shanmugasundram Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.88 KDM2B Achchuthan Shanmugasundram Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.87 KDM2B Achchuthan Shanmugasundram Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.88 KDM2B Achchuthan Shanmugasundram Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.88 KDM2B Achchuthan Shanmugasundram Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.88 KDM2B Achchuthan Shanmugasundram Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.87 KDM2B Achchuthan Shanmugasundram Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.88 KDM2B Achchuthan Shanmugasundram Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.88 KDM2B Achchuthan Shanmugasundram Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.87 KDM2B Achchuthan Shanmugasundram Phenotypes for gene: KDM2B were changed from to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.87 KDM2B Achchuthan Shanmugasundram Publications for gene: KDM2B were set to 36322151
Intellectual disability v5.87 KDM2B Achchuthan Shanmugasundram Publications for gene: KDM2B were set to PMID: 36322151; 35128353; 35710456
Intellectual disability v5.86 KDM2B Achchuthan Shanmugasundram reviewed gene: KDM2B: Rating: GREEN; Mode of pathogenicity: None; Publications: 36322151; Phenotypes: neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mosaic skin disorders - deep sequencing v2.1 AKT2 Tom Cullup edited their review of gene: AKT2: Added comment: Hot-spot variant Glu17Lys reported multiple times de novo, at least twice mosaic (21979934; 24285683); Changed rating: GREEN; 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; Changed publications to: 21979934, 24285683; Changed phenotypes to: hypoinsulinemic hypoglycemia with hemihypertrophy (HIHGHH) (MIM 240900)
Segmental overgrowth disorders - Deep sequencing v3.5 AKT2 Tom Cullup reviewed gene: AKT2: 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: 21979934, 24285683; Phenotypes: hypoinsulinemic hypoglycemia with hemihypertrophy (HIHGHH) (MIM 240900); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mosaic skin disorders - deep sequencing v2.1 GJA4 Tom Cullup gene: GJA4 was added
gene: GJA4 was added to Mosaic skin disorders - deep sequencing. Sources: Expert list
Mode of inheritance for gene: GJA4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GJA4 were set to 33912852
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
Review for gene: GJA4 was set to GREEN
Added comment: Multiple patients with shared phenotype and hot-spot Gly41Cys somatic gain of function mutation in 33912852.
Sources: Expert list
Mosaic skin disorders - deep sequencing v2.1 KITLG Tom Cullup edited their review of gene: KITLG: Added comment: Good evidence to support causation in familial progressive hyper- and hypopigmentation (FPHH) - green on pigmentary disorders panel. Less evidence to support linear and whorled nevoid hypermelanosis (LWNH) - single case in PMID 28257793, but important as differential for mosaic pigmentary disorders as no brain involvement unlike other similarly presenting disorders (therefore no brain scanning mandated following KITLG diagnosis).; Changed rating: GREEN; Changed publications to: 28257793; Changed phenotypes to: Linear and whorled nevoid hypermelanosis (LWNH), familial progressive hyperpigmentation with or without hypopigmentation (FPHH)(MIM 145250)
Mosaic skin disorders - deep sequencing v2.1 TP63 Tom Cullup gene: TP63 was added
gene: TP63 was added to Mosaic skin disorders - deep sequencing. Sources: Expert list
Mode of inheritance for gene: TP63 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TP63 were set to 18792980
Phenotypes for gene: TP63 were set to Split hand foot malformation with whorl-like pigmentary pattern
Penetrance for gene: TP63 were set to unknown
Review for gene: TP63 was set to GREEN
Added comment: Lots of evidence to support germline variation causing disease - 2x cases now identified as somatic mosaic with pigmentary anomalies (1x in literature, 1 x Kinsler lab). Gene can be rated green based on germline occurrences, and important to be able to detect somatic mosaics as a differential in cases of Blaschkolinear pigmentary anomalies.
Sources: Expert list
Mosaic skin disorders - deep sequencing v2.1 FGFR2 Tom Cullup edited their review of gene: FGFR2: Added comment: Sufficient evidence now to promote to green; Changed rating: GREEN; 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; Changed publications to: 31937562, 30580445, 30117157; Changed phenotypes to: Keratinocytic epidermal naevi (KENs), naevoid acanthosis nigricans or RAVEN (round and velvety epidermal naevus)
Bleeding and platelet disorders v3.2 ADAMTS13 Carl Fratter edited their review of gene: ADAMTS13: Added comment: Consensus opinion from the Central & South and South West haemostasis genomics MDT is that ADAMTS13 should be classified as a green gene on the R90 (bleeding and platelet disorders) panel. Laboratory findings in patients with congenital TTP include thrombocytopenia and this is not always readily distinguishable from other causes of thrombocytopenia.; Changed phenotypes to: 274150 Thrombotic thrombocytopenic purpura, hereditary; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.86 HNRNPD Achchuthan Shanmugasundram Publications for gene: HNRNPD were set to 33057194; 33874999
Intellectual disability v5.87 HNRNPD Achchuthan Shanmugasundram Publications for gene: HNRNPD were set to 33057194; 33874999
Intellectual disability v5.87 HNRNPD Achchuthan Shanmugasundram Publications for gene: HNRNPD were set to 33057194; 33874999
Intellectual disability v5.87 HNRNPD Achchuthan Shanmugasundram Publications for gene: HNRNPD were set to 33057194; 33874999
Intellectual disability v5.86 HNRNPD Achchuthan Shanmugasundram Publications for gene: HNRNPD were set to 33057194; 33874999
Intellectual disability v5.86 HNRNPD Achchuthan Shanmugasundram Publications for gene: HNRNPD were set to 33057194; 33874999
Intellectual disability v5.86 HNRNPD Achchuthan Shanmugasundram Publications for gene: HNRNPD were set to 33057194; 33874999
Intellectual disability v5.86 HNRNPD Achchuthan Shanmugasundram Publications for gene: HNRNPD were set to 33057194
Intellectual disability v5.85 HNRNPD Achchuthan Shanmugasundram Tag watchlist tag was added to gene: HNRNPD.
Intellectual disability v5.85 HNRNPD Achchuthan Shanmugasundram changed review comment from: As reviewed by Zornitza Stark (Australian Genomics), several additional individuals with neurodevelopmental disorders carrying de novo HNRNPD variants identified in an international cohort have been reported in PMID:33874999. These probands displayed a high prevalence of DD/ID, speech delay, and ASD and/or other behavioural phenotypes. As this is a large cohort study and there is no complete information about DD/ID phenotypes in these probands, this gene should remain as AMBER.; to: As reviewed by Zornitza Stark (Australian Genomics), several additional individuals with neurodevelopmental disorders carrying de novo HNRNPD variants identified in an international cohort have been reported in PMID:33874999. These probands displayed a high prevalence of DD/ID, speech delay, and ASD and/or other behavioural phenotypes. As this is a large cohort study and there is no complete information about DD/ID phenotypes in these probands, this gene should remain as AMBER.

The 'watchlist' tag has been added to review this rating in light of new evidence in the future.
Intellectual disability v5.85 HNRNPD Achchuthan Shanmugasundram reviewed gene: HNRNPD: Rating: AMBER; Mode of pathogenicity: None; Publications: 33874999; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mosaic skin disorders - deep sequencing v2.1 AKT3 Tom Cullup edited their review of gene: AKT3: Added comment: Previously not included in R327 (R110 only), but is a differential in patients referred for R327 only.; Changed rating: GREEN; 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; Changed publications to: 22500628, 22729224; Changed phenotypes to: megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome-2 (MPPH2) (615937)
Mosaic skin disorders - deep sequencing v2.1 ATP2A2 Tom Cullup reviewed gene: ATP2A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 11121153; Phenotypes: Segmental Darier disease (MIM 124200), Darier-White disease (MIM 124200), Acrokeratosis verruciformis (MIM 101900); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Limb disorders v4.3 CDX2 Arina Puzriakova Entity copied from Fetal anomalies v3.6
Limb disorders v4.3 CDX2 Arina Puzriakova gene: CDX2 was added
gene: CDX2 was added to Limb disorders. Sources: Expert Review Amber,Literature
Q2_23_promote_green tags were added to gene: CDX2.
Mode of inheritance for gene: CDX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDX2 were set to 29177441; 32058622; 34671974
Phenotypes for gene: CDX2 were set to Multiple congenital anomalies
Penetrance for gene: CDX2 were set to unknown
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.20 CASQ1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: CASQ1.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.20 CASQ1 Achchuthan Shanmugasundram Deleted their comment
VACTERL-like phenotypes v1.34 CDX2 Arina Puzriakova Publications for gene: CDX2 were set to PMID: 34671974
Fetal anomalies v3.6 CDX2 Arina Puzriakova Publications for gene: CDX2 were set to PMID: 34671974
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.20 CASQ1 Achchuthan Shanmugasundram Classified gene: CASQ1 as Amber List (moderate evidence)
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.20 CASQ1 Achchuthan Shanmugasundram Added comment: Comment on list classification: In addition to the original founder variant, at least five other variants from this gene were identified to be associated with myopathy. There is sufficient evidence available (>20 unrelated cases and functional studies) for this gene to be promoted to GREEN at the next GMS update.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.20 CASQ1 Achchuthan Shanmugasundram Gene: casq1 has been classified as Amber List (Moderate Evidence).
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.20 CASQ1 Achchuthan Shanmugasundram Classified gene: CASQ1 as Amber List (moderate evidence)
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.20 CASQ1 Achchuthan Shanmugasundram Added comment: Comment on list classification: In addition to the original founder variant, at least five other variants from this gene were identified to be associated with myopathy. There is sufficient evidence available (>20 unrelated cases and functional studies) for this gene to be promoted to GREEN at the next GMS update.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.20 CASQ1 Achchuthan Shanmugasundram Gene: casq1 has been classified as Amber List (Moderate Evidence).
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.19 CASQ1 Achchuthan Shanmugasundram Phenotypes for gene: CASQ1 were changed from Myopathy, vacuolar, with CASQ1 aggregates, OMIM:616231 to Myopathy, vacuolar, with CASQ1 aggregates, OMIM:616231
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.20 CASQ1 Achchuthan Shanmugasundram Phenotypes for gene: CASQ1 were changed from Myopathy, vacuolar, with CASQ1 aggregates, OMIM:616231 to Myopathy, vacuolar, with CASQ1 aggregates, OMIM:616231
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.20 CASQ1 Achchuthan Shanmugasundram Phenotypes for gene: CASQ1 were changed from Myopathy, vacuolar, with CASQ1 aggregates, OMIM:616231 to Myopathy, vacuolar, with CASQ1 aggregates, OMIM:616231
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.19 CASQ1 Achchuthan Shanmugasundram Phenotypes for gene: CASQ1 were changed from Myopathy, vacuolar, with CASQ1 aggregates, OMIM:616231 to Myopathy, vacuolar, with CASQ1 aggregates, OMIM:616231
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.19 CASQ1 Achchuthan Shanmugasundram Phenotypes for gene: CASQ1 were changed from Myopathy, vacuolar, with CASQ1 aggregates, 616231 to Myopathy, vacuolar, with CASQ1 aggregates, OMIM:616231
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.18 CASQ1 Achchuthan Shanmugasundram Publications for gene: CASQ1 were set to 26136523; 28895244; 29039140; 30258016; 34908252; 36514469
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.18 CASQ1 Achchuthan Shanmugasundram Publications for gene: CASQ1 were set to 26136523; 28895244; 29039140; 30258016; 34908252; 36514469
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.18 CASQ1 Achchuthan Shanmugasundram Publications for gene: CASQ1 were set to 26136523; 28895244; 29039140; 30258016; 34908252; 36514469
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.17 CASQ1 Achchuthan Shanmugasundram Publications for gene: CASQ1 were set to 26136523; 28895244; 29039140; 30258016; 34908252; 36514469
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.17 CASQ1 Achchuthan Shanmugasundram Publications for gene: CASQ1 were set to
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.16 CASQ1 Achchuthan Shanmugasundram Mode of inheritance for gene: CASQ1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.15 CASQ1 Achchuthan Shanmugasundram reviewed gene: CASQ1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26136523, 28895244, 29039140, 30258016, 34908252, 36514469; Phenotypes: Myopathy, vacuolar, with CASQ1 aggregates, OMIM:616231; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
VACTERL-like phenotypes v1.33 CDX2 Arina Puzriakova Classified gene: CDX2 as Green List (high evidence)
VACTERL-like phenotypes v1.33 CDX2 Arina Puzriakova Added comment: Comment on list classification: New gene added by Dmitrijs Rots (RadboudUMC). At least 8 unrelated families reported with de novo or inherited pathogenic variants in CDX2. Phenotypic findings comprise a broad spectrum of caudal abnormalities including defects of the uro‐recto‐genital tract, vertebrae, and the limbs. Cdx2 mutant mice show a variable phenotype that is comparable to that of patients (including imperforate anus, sirenomelia, posterior vertebral truncations, and bladder anomalies).

Overall there is sufficient evidence to promote this gene to Green as the clinical phenotype in some patients shows overlap with VACTERL.
VACTERL-like phenotypes v1.33 CDX2 Arina Puzriakova Gene: cdx2 has been classified as Green List (High Evidence).
Fetal anomalies v3.5 CDX2 Arina Puzriakova Classified gene: CDX2 as Amber List (moderate evidence)
Fetal anomalies v3.5 CDX2 Arina Puzriakova Added comment: Comment on list classification: New gene added by Dmitrijs Rots (RadboudUMC). At least 8 unrelated families reported with de novo or inherited pathogenic variants in CDX2. Phenotypic findings comprise a broad spectrum of caudal abnormalities including defects of the uro‐recto‐genital tract, vertebrae, and the limbs. Cdx2 mutant mice show a variable phenotype that is comparable to that of patients (including imperforate anus, sirenomelia, posterior vertebral truncations, and bladder anomalies).

Overall there is sufficient evidence to promote this gene to Green at the next GMS panel update.
Fetal anomalies v3.5 CDX2 Arina Puzriakova Gene: cdx2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v3.4 CDX2 Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: CDX2.
Fetal anomalies v3.4 AAAS Arina Puzriakova Classified gene: AAAS as Green List (high evidence)
Fetal anomalies v3.4 AAAS Arina Puzriakova Added comment: Comment on list classification: Maintaining Green rating as this gene was previously determined to be appropriate for this panel by the NHS GMS Fetal expert group at GOSH.
Fetal anomalies v3.4 AAAS Arina Puzriakova Gene: aaas has been classified as Green List (High Evidence).
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.15 STIM1 Achchuthan Shanmugasundram reviewed gene: STIM1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Myopathy, tubular aggregate, 1, OMIM:160565; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Likely inborn error of metabolism v4.27 PNPLA2 Achchuthan Shanmugasundram Classified gene: PNPLA2 as Amber List (moderate evidence)
Likely inborn error of metabolism v4.27 PNPLA2 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.
Likely inborn error of metabolism v4.27 PNPLA2 Achchuthan Shanmugasundram Gene: pnpla2 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v4.27 PNPLA2 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: PNPLA2.
Likely inborn error of metabolism v4.27 PNPLA2 Achchuthan Shanmugasundram Classified gene: PNPLA2 as Amber List (moderate evidence)
Likely inborn error of metabolism v4.27 PNPLA2 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.
Likely inborn error of metabolism v4.27 PNPLA2 Achchuthan Shanmugasundram Gene: pnpla2 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v4.27 PNPLA2 Achchuthan Shanmugasundram Classified gene: PNPLA2 as Amber List (moderate evidence)
Likely inborn error of metabolism v4.27 PNPLA2 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.
Likely inborn error of metabolism v4.27 PNPLA2 Achchuthan Shanmugasundram Gene: pnpla2 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v4.27 PNPLA2 Achchuthan Shanmugasundram Deleted their comment
Likely inborn error of metabolism v4.27 PNPLA2 Achchuthan Shanmugasundram Classified gene: PNPLA2 as Amber List (moderate evidence)
Likely inborn error of metabolism v4.27 PNPLA2 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.
Likely inborn error of metabolism v4.27 PNPLA2 Achchuthan Shanmugasundram Gene: pnpla2 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v4.27 PNPLA2 Achchuthan Shanmugasundram Publications for gene: PNPLA2 were set to 18952067; 21544567; 25287355; 25956450; 32269696
Likely inborn error of metabolism v4.27 PNPLA2 Achchuthan Shanmugasundram Classified gene: PNPLA2 as Amber List (moderate evidence)
Likely inborn error of metabolism v4.27 PNPLA2 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.
Likely inborn error of metabolism v4.27 PNPLA2 Achchuthan Shanmugasundram Gene: pnpla2 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v4.26 PNPLA2 Achchuthan Shanmugasundram Publications for gene: PNPLA2 were set to 18952067; 21544567; 25287355; 25956450; 32269696
Likely inborn error of metabolism v4.27 PNPLA2 Achchuthan Shanmugasundram Publications for gene: PNPLA2 were set to 18952067; 21544567; 25287355; 25956450; 32269696
Likely inborn error of metabolism v4.27 PNPLA2 Achchuthan Shanmugasundram Publications for gene: PNPLA2 were set to 18952067; 21544567; 25287355; 25956450; 32269696
Likely inborn error of metabolism v4.26 PNPLA2 Achchuthan Shanmugasundram Publications for gene: PNPLA2 were set to 18952067; 21544567; 25287355; 25956450; 32269696
Likely inborn error of metabolism v4.26 PNPLA2 Achchuthan Shanmugasundram Publications for gene: PNPLA2 were set to 18952067; 21544567; 25287355; 25956450; 32269696
Likely inborn error of metabolism v4.26 PNPLA2 Achchuthan Shanmugasundram Publications for gene: PNPLA2 were set to 18952067; 21544567; 25287355; 25956450; 32269696
Likely inborn error of metabolism v4.26 PNPLA2 Achchuthan Shanmugasundram Publications for gene: PNPLA2 were set to 18952067; 25287355; 25956450
Likely inborn error of metabolism v4.25 PNPLA2 Achchuthan Shanmugasundram reviewed gene: PNPLA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 18952067, 21544567, 25287355, 25956450, 32269696; Phenotypes: Neutral lipid storage disease with myopathy, OMIM:610717; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.15 PNPLA2 Achchuthan Shanmugasundram Publications for gene: PNPLA2 were set to 32269696; 21544567
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.14 PNPLA2 Achchuthan Shanmugasundram edited their review of gene: PNPLA2: Changed publications to: 18952067, 21544567, 25956450, 32269696
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.14 PNPLA2 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: PNPLA2.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.14 PNPLA2 Achchuthan Shanmugasundram Classified gene: PNPLA2 as Amber List (moderate evidence)
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.14 PNPLA2 Achchuthan Shanmugasundram Gene: pnpla2 has been classified as Amber List (Moderate Evidence).
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.14 PNPLA2 Achchuthan Shanmugasundram Classified gene: PNPLA2 as Amber List (moderate evidence)
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.14 PNPLA2 Achchuthan Shanmugasundram Gene: pnpla2 has been classified as Amber List (Moderate Evidence).
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.13 PNPLA2 Achchuthan Shanmugasundram reviewed gene: PNPLA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 21544567, 32269696; Phenotypes: Neutral lipid storage disease with myopathy, OMIM:610717; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.13 BVES Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: BVES.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.13 BVES Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Zornitza Stark (Australian Genomics), there is sufficient evidence (five unrelated cases) for this gene to be promoted to GREEN at the next major review.; to: Comment on list classification: As reviewed by Zornitza Stark (Australian Genomics), there is sufficient evidence (five unrelated cases) for this gene to be promoted to GREEN at the next major review. All these patients showed limb-girdle muscular weakness/ dystrophy.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.13 BVES Achchuthan Shanmugasundram Publications for gene: BVES were set to 26642364; 31119192; 32528171
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.13 BVES Achchuthan Shanmugasundram Publications for gene: BVES were set to 26642364
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.12 BVES Achchuthan Shanmugasundram Classified gene: BVES as Amber List (moderate evidence)
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.12 BVES Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark (Australian Genomics), there is sufficient evidence (five unrelated cases) for this gene to be promoted to GREEN at the next major review.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.12 BVES Achchuthan Shanmugasundram Gene: bves has been classified as Amber List (Moderate Evidence).
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.11 BVES Achchuthan Shanmugasundram reviewed gene: BVES: Rating: GREEN; Mode of pathogenicity: None; Publications: 26642364, 31119192, 32528171; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 25, OMIM:616812; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.85 WIPI2 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Zornitza Stark (Australian Genomics), there are three unrelated families with homozygous variants in WIPI2 gene presenting with varying degrees of intellectual disability supported by functional evidence. Hence, this gene can be promoted to GREEN at the next major review.; to: Comment on list classification: As reviewed by Zornitza Stark (Australian Genomics), there are three unrelated families with homozygous variants in WIPI2 gene presenting with varying degrees of intellectual disability (moderate to profound) and supported by functional evidence. Hence, this gene can be promoted to GREEN at the next major review.
Intellectual disability v5.85 WIPI2 Achchuthan Shanmugasundram Publications for gene: WIPI2 were set to 30968111; 34557665
Intellectual disability v5.84 WIPI2 Achchuthan Shanmugasundram Publications for gene: WIPI2 were set to 30968111; 34557665
Intellectual disability v5.84 WIPI2 Achchuthan Shanmugasundram Publications for gene: WIPI2 were set to 30968111; 34557665
Intellectual disability v5.84 WIPI2 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: WIPI2.
Intellectual disability v5.84 WIPI2 Achchuthan Shanmugasundram Publications for gene: WIPI2 were set to 30968111; 34557665
Intellectual disability v5.83 WIPI2 Achchuthan Shanmugasundram Publications for gene: WIPI2 were set to 30968111; 34557665
Intellectual disability v5.84 WIPI2 Achchuthan Shanmugasundram Publications for gene: WIPI2 were set to 30968111
Intellectual disability v5.83 WIPI2 Achchuthan Shanmugasundram Classified gene: WIPI2 as Amber List (moderate evidence)
Intellectual disability v5.83 WIPI2 Achchuthan Shanmugasundram Gene: wipi2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.83 WIPI2 Achchuthan Shanmugasundram Classified gene: WIPI2 as Amber List (moderate evidence)
Intellectual disability v5.83 WIPI2 Achchuthan Shanmugasundram Gene: wipi2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.83 WIPI2 Achchuthan Shanmugasundram Classified gene: WIPI2 as Amber List (moderate evidence)
Intellectual disability v5.83 WIPI2 Achchuthan Shanmugasundram Gene: wipi2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.82 WIPI2 Achchuthan Shanmugasundram Classified gene: WIPI2 as Amber List (moderate evidence)
Intellectual disability v5.82 WIPI2 Achchuthan Shanmugasundram Gene: wipi2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.81 WIPI2 Achchuthan Shanmugasundram Classified gene: WIPI2 as Red List (low evidence)
Intellectual disability v5.81 WIPI2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark (Australian Genomics), there are three unrelated families with homozygous variants in WIPI2 gene presenting with varying degrees of intellectual disability supported by functional evidence. Hence, this gene can be promoted to GREEN at the next major review.
Intellectual disability v5.81 WIPI2 Achchuthan Shanmugasundram Gene: wipi2 has been classified as Red List (Low Evidence).
Intellectual disability v5.80 WIPI2 Achchuthan Shanmugasundram reviewed gene: WIPI2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30968111, 34557665; Phenotypes: ?Intellectual developmental disorder with short stature and variable skeletal anomalies, OMIM:618453; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v4.20 PLXNA1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: PLXNA1.
Early onset or syndromic epilepsy v4.20 PLXNA1 Achchuthan Shanmugasundram Deleted their comment
Early onset or syndromic epilepsy v4.20 PLXNA1 Achchuthan Shanmugasundram Classified gene: PLXNA1 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.20 PLXNA1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (five unrelated cases) available for associating monoallelic variants in this gene with epilepsy/ seizures with a GREEN rating and hence this gene can be promoted at the next major review.
Early onset or syndromic epilepsy v4.20 PLXNA1 Achchuthan Shanmugasundram Gene: plxna1 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.20 PLXNA1 Achchuthan Shanmugasundram Classified gene: PLXNA1 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.20 PLXNA1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (five unrelated cases) available for associating monoallelic variants in this gene with epilepsy/ seizures with a GREEN rating and hence this gene can be promoted at the next major review.
Early onset or syndromic epilepsy v4.20 PLXNA1 Achchuthan Shanmugasundram Gene: plxna1 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.19 PLXNA1 Achchuthan Shanmugasundram gene: PLXNA1 was added
gene: PLXNA1 was added to Early onset or syndromic epilepsy. Sources: Literature
Mode of inheritance for gene: PLXNA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PLXNA1 were set to 28464511; 34054129
Phenotypes for gene: PLXNA1 were set to developmental and epileptic encephalopathy, MONDO:0100062
Review for gene: PLXNA1 was set to GREEN
Added comment: Monoallelic cases:

PMID:28464511 reported a male patient with a de novo variant in PLXNA1 and presenting with intractable infantile onset epilepsy, and intellectual disability with autism spectrum disorder. In addition, this patient also had features suggestive of Dubowitz syndrome, including growth failure, dermatologic symptoms, and characteristic dysmorphic facial features. It has also been reviewed in this publication that one of only two previously reported cases with missense PLXNA1 variants had epileptic encephalopathy.

PMID:34054129 reported ten cases from seven families with PLXNA1 variants. Of these cases, three unrelated cases had monoallelic de novo variants and presented with global developmental delay, seizures and craniofacial, brain and eye anomalies.


Biallelic cases:

Out of ten cases reported in PMID:34054129, seven cases from four unrelated families exhibited biallelic variants in PLXNA1 gene. They presented with global developmental delay and craniofacial, brain and eye anomalies. However, seizures are not reported in biallelic cases except one family (15 episodes of febrile and nonfebrile seizures reported in family A).

The biallelic variants in this gene has been associated with phenotypes in OMIM (MIM #619955). However, both monoalellic and biallelic variants in this gene has been associated with phenotypes in Gene2Phenotype (with 'limited' rating).

Functional studies:

Structural modeling of missense variants in PLXNA1 suggests distortion in the native protein. Knockdown of plxna1a leads to cerebral anomalies and eye anomalies in zebrafish larvae.
Sources: Literature
Intellectual disability v5.80 PLXNA1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: PLXNA1.
Intellectual disability v5.80 PLXNA1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.80 PLXNA1 Achchuthan Shanmugasundram Classified gene: PLXNA1 as Amber List (moderate evidence)
Intellectual disability v5.80 PLXNA1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for this gene to be promoted to GREEN at the next major review. The MOI can also be set to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal" as there are more than three cases each with both monoallelic and biallelic variants.
Intellectual disability v5.80 PLXNA1 Achchuthan Shanmugasundram Gene: plxna1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.79 PLXNA1 Achchuthan Shanmugasundram Classified gene: PLXNA1 as Amber List (moderate evidence)
Intellectual disability v5.79 PLXNA1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for this gene to be promoted to GREEN at the next major review. The MOI can also be set to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal" as there are more than three cases each with both monoallelic and biallelic variants.
Intellectual disability v5.79 PLXNA1 Achchuthan Shanmugasundram Gene: plxna1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.78 PLXNA1 Achchuthan Shanmugasundram Phenotypes for gene: PLXNA1 were changed from Dworschak-Punetha neurodevelopmental syndrome, OMIM:619955; developmental and epileptic encephalopathy, MONDO:0100062 to Dworschak-Punetha neurodevelopmental syndrome, OMIM:619955; developmental and epileptic encephalopathy, MONDO:0100062
Intellectual disability v5.78 PLXNA1 Achchuthan Shanmugasundram Phenotypes for gene: PLXNA1 were changed from Dworschak-Punetha neurodevelopmental syndrome, OMIM:619955; developmental and epileptic encephalopathy, MONDO:0100062 to Dworschak-Punetha neurodevelopmental syndrome, OMIM:619955; developmental and epileptic encephalopathy, MONDO:0100062
Intellectual disability v5.78 PLXNA1 Achchuthan Shanmugasundram Phenotypes for gene: PLXNA1 were changed from Dworschak-Punetha neurodevelopmental syndrome, OMIM:619955; developmental and epileptic encephalopathy, MONDO:0100062 to Dworschak-Punetha neurodevelopmental syndrome, OMIM:619955; developmental and epileptic encephalopathy, MONDO:0100062
Intellectual disability v5.78 PLXNA1 Achchuthan Shanmugasundram Phenotypes for gene: PLXNA1 were changed from Dworschak-Punetha neurodevelopmental syndrome, OMIM:619955; developmental and epileptic encephalopathy, MONDO:0100062 to Dworschak-Punetha neurodevelopmental syndrome, OMIM:619955; developmental and epileptic encephalopathy, MONDO:0100062
Intellectual disability v5.78 PLXNA1 Achchuthan Shanmugasundram Phenotypes for gene: PLXNA1 were changed from Neurodevelopmental disorder with cerebral and eye anomalies; Dworschak-Punetha neurodevelopmental syndrome, OMIM:619955; developmental and epileptic encephalopathy, MONDO:0100062 to Dworschak-Punetha neurodevelopmental syndrome, OMIM:619955; developmental and epileptic encephalopathy, MONDO:0100062
Intellectual disability v5.77 PLXNA1 Achchuthan Shanmugasundram Phenotypes for gene: PLXNA1 were changed from Neurodevelopmental disorder with cerebral and eye anomalies; Dworschak-Punetha neurodevelopmental syndrome, OMIM:619955; developmental and epileptic encephalopathy, MONDO:0100062 to Neurodevelopmental disorder with cerebral and eye anomalies; Dworschak-Punetha neurodevelopmental syndrome, OMIM:619955; developmental and epileptic encephalopathy, MONDO:0100062
Intellectual disability v5.77 PLXNA1 Achchuthan Shanmugasundram Phenotypes for gene: PLXNA1 were changed from Neurodevelopmental disorder with cerebral and eye anomalies; Dworschak-Punetha neurodevelopmental syndrome, OMIM:619955; developmental and epileptic encephalopathy, MONDO:0100062 to Neurodevelopmental disorder with cerebral and eye anomalies; Dworschak-Punetha neurodevelopmental syndrome, OMIM:619955; developmental and epileptic encephalopathy, MONDO:0100062
Intellectual disability v5.77 PLXNA1 Achchuthan Shanmugasundram Phenotypes for gene: PLXNA1 were changed from Neurodevelopmental disorder with cerebral and eye anomalies to Neurodevelopmental disorder with cerebral and eye anomalies; Dworschak-Punetha neurodevelopmental syndrome, OMIM:619955; developmental and epileptic encephalopathy, MONDO:0100062
Intellectual disability v5.76 PLXNA1 Achchuthan Shanmugasundram Publications for gene: PLXNA1 were set to 28464511; 34054129; 34415653
Intellectual disability v5.76 PLXNA1 Achchuthan Shanmugasundram Publications for gene: PLXNA1 were set to 34054129
Intellectual disability v5.75 PLXNA1 Achchuthan Shanmugasundram Deleted their review
Intellectual disability v5.75 PLXNA1 Achchuthan Shanmugasundram reviewed gene: PLXNA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28464511, 34054129, 34415653; Phenotypes: Dworschak-Punetha neurodevelopmental syndrome, OMIM:619955, developmental and epileptic encephalopathy, MONDO:0100062; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v5.75 PLXNA1 Achchuthan Shanmugasundram reviewed gene: PLXNA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28464511, 34054129, 34415653; Phenotypes: Dworschak-Punetha neurodevelopmental syndrome, OMIM:619955, developmental and epileptic encephalopathy, MONDO:0100062; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v5.75 KIF4A Achchuthan Shanmugasundram Phenotypes for gene: KIF4A were changed from ?Intellectual developmental disorder, X-linked 100, OMIM:300923 to ?Intellectual developmental disorder, X-linked 100, OMIM:300923
Intellectual disability v5.75 KIF4A Achchuthan Shanmugasundram Phenotypes for gene: KIF4A were changed from ?Intellectual developmental disorder, X-linked 100, OMIM:300923 to ?Intellectual developmental disorder, X-linked 100, OMIM:300923
Intellectual disability v5.75 KIF4A Achchuthan Shanmugasundram Phenotypes for gene: KIF4A were changed from ?Intellectual developmental disorder, X-linked 100, OMIM:300923 to ?Intellectual developmental disorder, X-linked 100, OMIM:300923
Intellectual disability v5.75 KIF4A Achchuthan Shanmugasundram Phenotypes for gene: KIF4A were changed from ?Intellectual developmental disorder, X-linked 100, OMIM:300923 to ?Intellectual developmental disorder, X-linked 100, OMIM:300923
Intellectual disability v5.74 KIF4A Achchuthan Shanmugasundram Phenotypes for gene: KIF4A were changed from ?Intellectual developmental disorder, X-linked 100, OMIM:300923 to ?Intellectual developmental disorder, X-linked 100, OMIM:300923
Intellectual disability v5.75 KIF4A Achchuthan Shanmugasundram Phenotypes for gene: KIF4A were changed from ?Intellectual developmental disorder, X-linked 100, OMIM:300923 to ?Intellectual developmental disorder, X-linked 100, OMIM:300923
Intellectual disability v5.75 KIF4A Achchuthan Shanmugasundram Phenotypes for gene: KIF4A were changed from ?Intellectual developmental disorder, X-linked 100, OMIM:300923 to ?Intellectual developmental disorder, X-linked 100, OMIM:300923
Intellectual disability v5.74 KIF4A Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: KIF4A.
Intellectual disability v5.74 KIF4A Achchuthan Shanmugasundram Phenotypes for gene: KIF4A were changed from ?Intellectual developmental disorder, X-linked 100, OMIM:300923 to ?Intellectual developmental disorder, X-linked 100, OMIM:300923
Intellectual disability v5.75 KIF4A Achchuthan Shanmugasundram Phenotypes for gene: KIF4A were changed from ?Intellectual developmental disorder, X-linked 100, OMIM:300923 to ?Intellectual developmental disorder, X-linked 100, OMIM:300923
Intellectual disability v5.75 KIF4A Achchuthan Shanmugasundram Phenotypes for gene: KIF4A were changed from ?Intellectual developmental disorder, X-linked 100, OMIM:300923 to ?Intellectual developmental disorder, X-linked 100, OMIM:300923
Intellectual disability v5.75 KIF4A Achchuthan Shanmugasundram Phenotypes for gene: KIF4A were changed from ?Intellectual developmental disorder, X-linked 100, OMIM:300923 to ?Intellectual developmental disorder, X-linked 100, OMIM:300923
Intellectual disability v5.74 KIF4A Achchuthan Shanmugasundram Phenotypes for gene: KIF4A were changed from ?Intellectual developmental disorder, X-linked 100, OMIM:300923 to ?Intellectual developmental disorder, X-linked 100, OMIM:300923
Intellectual disability v5.75 KIF4A Achchuthan Shanmugasundram Phenotypes for gene: KIF4A were changed from ?Intellectual developmental disorder, X-linked 100, OMIM:300923 to ?Intellectual developmental disorder, X-linked 100, OMIM:300923
Intellectual disability v5.74 KIF4A Achchuthan Shanmugasundram Publications for gene: KIF4A were set to 24812067; 34346154
Intellectual disability v5.74 KIF4A Achchuthan Shanmugasundram Phenotypes for gene: KIF4A were changed from ?Intellectual developmental disorder, X-linked 100, OMIM:300923 to ?Intellectual developmental disorder, X-linked 100, OMIM:300923
Intellectual disability v5.74 KIF4A Achchuthan Shanmugasundram Phenotypes for gene: KIF4A were changed from ?Intellectual developmental disorder, X-linked 100, OMIM:300923 to ?Intellectual developmental disorder, X-linked 100, OMIM:300923
Intellectual disability v5.74 KIF4A Achchuthan Shanmugasundram Phenotypes for gene: KIF4A were changed from INTELLECTUAL DISABILITY to ?Intellectual developmental disorder, X-linked 100, OMIM:300923
Intellectual disability v5.74 KIF4A Achchuthan Shanmugasundram Publications for gene: KIF4A were set to 24812067; 34346154
Intellectual disability v5.73 KIF4A Achchuthan Shanmugasundram Publications for gene: KIF4A were set to 24812067; 34346154
Intellectual disability v5.73 KIF4A Achchuthan Shanmugasundram Publications for gene: KIF4A were set to 24812067
Intellectual disability v5.72 KIF4A Achchuthan Shanmugasundram Classified gene: KIF4A as Amber List (moderate evidence)
Intellectual disability v5.72 KIF4A Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark (Australian Genomics), there are at least four unrelated cases with hemizygous variants in KIF4A gene and presenting with intellectual disability. This evidence is sufficient for promoting to GREEN rating at the next major review.
Intellectual disability v5.72 KIF4A Achchuthan Shanmugasundram Gene: kif4a has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.71 KIF4A Achchuthan Shanmugasundram changed review comment from: As reviewed by Zornitza Stark (Australian Genomics), there are at least four unrelated cases with hemizygous variants in KIF4A gene and presenting with intellectual disability.

PMID:24812067 reported a family in which five males spanning three generations had intellectual disability, speech delay and global developmental delay and four of these males developed seizures in late childhood–adolescence.

PMID:34346154 reported 11 unrelated cases expanding the phenotypic spectrum to include developmental delay and intellectual disability with or without epilepsy to a congenital anomaly phenotype with hydrocephalus and various brain anomalies at the more severe end of clinical manifestations. Of eight patients with congenital anomalies, one each had severe to profound developmental delay, mild psychomotor delay and severe psychomotor delay, while the remaining five had no developmental delays. However, all three patients without congenital structural anomalies had intellectual disability (borderline intellectual functioning in one case), speech delay and global developmental delay, while motor delay and autism spectrum disorder was reported in two cases each. Isolated febrile seizure was reported in one case.

This gene has been reported in OMIM (MIM #300923) and Gene2Phenotype (with 'limited' rating) on the basis of one family from PMID:24812067.; to: PMID:24812067 reported a family in which five males spanning three generations had intellectual disability, speech delay and global developmental delay and four of these males developed seizures in late childhood–adolescence.

PMID:34346154 reported 11 unrelated cases expanding the phenotypic spectrum to include developmental delay and intellectual disability with or without epilepsy to a congenital anomaly phenotype with hydrocephalus and various brain anomalies at the more severe end of clinical manifestations. Of eight patients with congenital anomalies, one each had severe to profound developmental delay, mild psychomotor delay and severe psychomotor delay, while the remaining five had no developmental delays. However, all three patients without congenital structural anomalies had intellectual disability (borderline intellectual functioning in one case), speech delay and global developmental delay, while motor delay and autism spectrum disorder was reported in two cases each. Isolated febrile seizure was reported in one case.

This gene has been reported in OMIM (MIM #300923) and Gene2Phenotype (with 'limited' rating) on the basis of one family from PMID:24812067.
Intellectual disability v5.71 KIF4A Achchuthan Shanmugasundram changed review comment from: As reviewed by Zornitza Stark (Australian Genomics), there are at least four unrelated cases with hemizygous variants in KIF4A gene and presenting with intellectual disability.

PMID:24812067 reported a family in which five males spanning three generations had intellectual disability, speech delay and global developmental delay and four of these males developed seizures in late childhood–adolescence.

PMID:34346154 reported 11 unrelated cases expanding the phenotypic spectrum to include developmental delay and intellectual disability with or without epilepsy to a congenital anomaly phenotype with hydrocephalus and various brain anomalies at the more severe end of clinical manifestations. Of eight patients with congenital anomalies, one each had severe to profound developmental delay, mild psychomotor delay and severe psychomotor delay, while the remaining five had no developmental delays. However, all three patients without congenital structural anomalies had intellectual disability (borderline intellectual functioning in one case), speech delay and global developmental delay, while motor delay and autism spectrum disorder was reported in two cases each. Isolated febrile seizure was reported in one case.; to: As reviewed by Zornitza Stark (Australian Genomics), there are at least four unrelated cases with hemizygous variants in KIF4A gene and presenting with intellectual disability.

PMID:24812067 reported a family in which five males spanning three generations had intellectual disability, speech delay and global developmental delay and four of these males developed seizures in late childhood–adolescence.

PMID:34346154 reported 11 unrelated cases expanding the phenotypic spectrum to include developmental delay and intellectual disability with or without epilepsy to a congenital anomaly phenotype with hydrocephalus and various brain anomalies at the more severe end of clinical manifestations. Of eight patients with congenital anomalies, one each had severe to profound developmental delay, mild psychomotor delay and severe psychomotor delay, while the remaining five had no developmental delays. However, all three patients without congenital structural anomalies had intellectual disability (borderline intellectual functioning in one case), speech delay and global developmental delay, while motor delay and autism spectrum disorder was reported in two cases each. Isolated febrile seizure was reported in one case.

This gene has been reported in OMIM (MIM #300923) and Gene2Phenotype (with 'limited' rating) on the basis of one family from PMID:24812067.
Intellectual disability v5.71 KIF4A Achchuthan Shanmugasundram reviewed gene: KIF4A: Rating: GREEN; Mode of pathogenicity: None; Publications: 24812067, 34346154; Phenotypes: ?Intellectual developmental disorder, X-linked 100, OMIM:300923; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v5.6 SVIL Achchuthan Shanmugasundram Classified gene: SVIL as Amber List (moderate evidence)
Arthrogryposis v5.6 SVIL Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as there is only limited evidence available: Two unrelated cases of myofibrillar myopathy (MIM #619040) with contractures.
Arthrogryposis v5.6 SVIL Achchuthan Shanmugasundram Gene: svil has been classified as Amber List (Moderate Evidence).
Arthrogryposis v5.5 SVIL Achchuthan Shanmugasundram Phenotypes for gene: SVIL were changed from myopathy; contractures; raised CK to Myofibrillar myopathy 10, OMIM:619040
Arthrogryposis v5.4 SVIL Achchuthan Shanmugasundram reviewed gene: SVIL: Rating: AMBER; Mode of pathogenicity: None; Publications: 32779703; Phenotypes: Myofibrillar myopathy 10, OMIM:619040; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.71 DDX23 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: DDX23.
Intellectual disability v5.71 DDX23 Achchuthan Shanmugasundram Classified gene: DDX23 as Amber List (moderate evidence)
Intellectual disability v5.71 DDX23 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next GMS review.
Intellectual disability v5.71 DDX23 Achchuthan Shanmugasundram Gene: ddx23 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.70 DDX23 Achchuthan Shanmugasundram reviewed gene: DDX23: Rating: GREEN; Mode of pathogenicity: None; Publications: 34050707; Phenotypes: global developmental delay with speech and behavioral abnormalities, MONDO:0030995; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v3.22 ARHGEF10 Achchuthan Shanmugasundram Publications for gene: ARHGEF10 were set to 14508709
Hereditary neuropathy or pain disorder v3.21 ARHGEF10 Achchuthan Shanmugasundram reviewed gene: ARHGEF10: Rating: AMBER; Mode of pathogenicity: None; Publications: 14508709, 21719701, 25025039, 25275565; Phenotypes: ?Slowed nerve conduction velocity, AD, OMIM:608236; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v3.21 UBA1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: UBA1.
Hereditary neuropathy or pain disorder v3.21 UBA1 Achchuthan Shanmugasundram Classified gene: UBA1 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v3.21 UBA1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (at least nine unrelated cases and supportive functional evidence) available for this gene to be promoted to GREEN at the next major review.
Hereditary neuropathy or pain disorder v3.21 UBA1 Achchuthan Shanmugasundram Gene: uba1 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v3.20 UBA1 Achchuthan Shanmugasundram Phenotypes for gene: UBA1 were changed from Spinal muscular atrophy, X-linked 2, infantile MIM#301830 to Spinal muscular atrophy, X-linked 2, infantile, OMIM:301830
Hereditary neuropathy or pain disorder v3.19 UBA1 Achchuthan Shanmugasundram Publications for gene: UBA1 were set to 18179898
Hereditary neuropathy or pain disorder v3.18 UBA1 Achchuthan Shanmugasundram changed review comment from: As reported in PMID:18179898 and reviewed in OMIM, X-linked spinal muscular atrophy-2 (SMAX2) is characterised by neonatal onset of severe hypotonia, areflexia, and multiple congenital contractures, known as arthrogryposis, associated with loss of anterior horn cells and infantile death. Variants in UBA1 gene ( p.Asn577Asn in three families, and p.Met539Ile and p.Ser547Gly in one family each) were identified in five of screened X-linked spinal muscular atrophy families.

Additional unrelated cases with variants in UBA1 gene are reported in PMIDs: 23518311, 26028276, 31932168 & 32181232.

This gene has been reported with relevant phenotypes in OMIM (MIM #301830).; to: As reported in PMID:18179898 and reviewed in OMIM, X-linked spinal muscular atrophy-2 (SMAX2) is characterised by neonatal onset of severe hypotonia, areflexia, and multiple congenital contractures, known as arthrogryposis, associated with loss of anterior horn cells and infantile death. Variants in UBA1 gene ( p.Asn577Asn in three families, and p.Met539Ile and p.Ser547Gly in one family each) were identified in five of screened X-linked spinal muscular atrophy families.

Additional unrelated cases with variants in UBA1 gene are reported in PMIDs: 23518311, 26028276, 31932168 & 32181232.

This gene has been reported with relevant phenotypes in OMIM (MIM #301830).
Hereditary neuropathy or pain disorder v3.18 UBA1 Achchuthan Shanmugasundram edited their review of gene: UBA1: Changed publications to: 18179898, 23518311, 26028276, 27699224, 29034082, 31932168, 32181232
Hereditary neuropathy or pain disorder v3.18 UBA1 Achchuthan Shanmugasundram reviewed gene: UBA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18179898, 23518311, 26028276, 31932168, 32181232; Phenotypes: Spinal muscular atrophy, X-linked 2, infantile, OMIM:301830; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Hereditary neuropathy or pain disorder v3.18 VAPB Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: VAPB.
Hereditary neuropathy or pain disorder v3.18 VAPB Achchuthan Shanmugasundram Classified gene: VAPB as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v3.18 VAPB Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (>3 unrelated cases & functional studies from mouse models) for this gene to be promoted to GREEN at the next major review.
Hereditary neuropathy or pain disorder v3.18 VAPB Achchuthan Shanmugasundram Gene: vapb has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v3.17 VAPB Achchuthan Shanmugasundram Phenotypes for gene: VAPB were changed from Adult proximal spinal muscular atrophy, autosomal dominant; dHMN/dSMA; Spinal muscular atrophy, late-onset, Finkel type, MIM# 182980 to Spinal muscular atrophy, late-onset, Finkel type, OMIM:182980; Amyotrophic lateral sclerosis 8, OMIM:608627
Hereditary neuropathy or pain disorder v3.16 VAPB Achchuthan Shanmugasundram Publications for gene: VAPB were set to 15372378; 32162544; 28993872; 28173107; 26566915
Hereditary neuropathy or pain disorder v3.15 VAPB Achchuthan Shanmugasundram reviewed gene: VAPB: Rating: GREEN; Mode of pathogenicity: None; Publications: 15372378, 20940299, 28173107, 28993872, 3216254; Phenotypes: Spinal muscular atrophy, late-onset, Finkel type, OMIM:182980, Amyotrophic lateral sclerosis 8, OMIM:608627; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebellar hypoplasia v1.72 HEATR5B Karen Stals changed review comment from: Four affected children from two families presenting with pontocerebellar hypoplasia with neonatal seizures, severe ID and motor delay. Additional family identified through the R14 WGS service in the Exeter Genomics Laboratory with the causative variant co-segregating in multiple affected family members.; to: Four affected children from two families presenting with pontocerebellar hypoplasia with neonatal seizures, severe ID and motor delay reported by Ghosh et al 2021. Additional family identified through the R14 WGS service in the Exeter Genomics Laboratory with the causative variant co-segregating in multiple affected family members.
Cerebellar hypoplasia v1.72 HEATR5B Karen Stals reviewed gene: HEATR5B: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33824466; Phenotypes: Pontocerebellar hypoplasia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability v5.70 INTS11 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: INTS11.
Intellectual disability v5.70 INTS11 Achchuthan Shanmugasundram changed review comment from: PMID:37054711 reported ten unrelated families with biallelic variants in INTS11 gene and they present with intellectual disability, global developmental and language delay, impaired motor development, and brain atrophy.

Functional studies in Drosophila showed that dIntS11 (fly ortholog of INTS11) is essential and expressed in the central nervous systems in a subset of neurons and most glia in larval and adult stages. In addition, genes with two variants (p.Arg17Leu and p.His414Tyr) fail to rescue the lethality of null mutants in the Drosophila model, indicating that they are strong loss-of-function variants. The other five variants (p.Gly55Ser, p.Leu138Phe, p.Lys396Glu, p.Val517Met and p.Ile553Glu) rescue lethality but cause a shortened lifespan and bang sensitivity and affect locomotor activity, indicating that they are partial loss-of-function variants.
Sources: Literature; to: PMID:37054711 reported ten unrelated families with biallelic variants in INTS11 gene and they present with intellectual disability, global developmental and language delay, impaired motor development, and brain atrophy.

Functional studies in Drosophila showed that dIntS11 (fly ortholog of INTS11) is essential and expressed in the central nervous systems in a subset of neurons and most glia in larval and adult stages. In addition, genes with two variants (p.Arg17Leu and p.His414Tyr) fail to rescue the lethality of null mutants in the Drosophila model, indicating that they are strong loss-of-function variants. The other five variants (p.Gly55Ser, p.Leu138Phe, p.Lys396Glu, p.Val517Met and p.Ile553Glu) rescue lethality but cause a shortened lifespan and bang sensitivity and affect locomotor activity, indicating that they are partial loss-of-function variants.

This gene has not yet been associated with relevant phenotypes in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability v5.70 INTS11 Achchuthan Shanmugasundram Classified gene: INTS11 as Amber List (moderate evidence)
Intellectual disability v5.70 INTS11 Achchuthan Shanmugasundram Gene: ints11 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.69 INTS11 Achchuthan Shanmugasundram Classified gene: INTS11 as Amber List (moderate evidence)
Intellectual disability v5.69 INTS11 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (10 unrelated cases and supporting functional evidence) for this gene to be promoted to green at the next major review.
Intellectual disability v5.69 INTS11 Achchuthan Shanmugasundram Gene: ints11 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.68 INTS11 Achchuthan Shanmugasundram gene: INTS11 was added
gene: INTS11 was added to Intellectual disability - microarray and sequencing. Sources: Literature
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 intellectual disability, MONDO:0001071
Review for gene: INTS11 was set to GREEN
Added comment: PMID:37054711 reported ten unrelated families with biallelic variants in INTS11 gene and they present with intellectual disability, global developmental and language delay, impaired motor development, and brain atrophy.

Functional studies in Drosophila showed that dIntS11 (fly ortholog of INTS11) is essential and expressed in the central nervous systems in a subset of neurons and most glia in larval and adult stages. In addition, genes with two variants (p.Arg17Leu and p.His414Tyr) fail to rescue the lethality of null mutants in the Drosophila model, indicating that they are strong loss-of-function variants. The other five variants (p.Gly55Ser, p.Leu138Phe, p.Lys396Glu, p.Val517Met and p.Ile553Glu) rescue lethality but cause a shortened lifespan and bang sensitivity and affect locomotor activity, indicating that they are partial loss-of-function variants.
Sources: Literature
Hereditary neuropathy or pain disorder v3.15 DRP2 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: DRP2.
Hereditary neuropathy or pain disorder v3.15 DRP2 Achchuthan Shanmugasundram Classified gene: DRP2 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v3.15 DRP2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark (Australian Genomics), there is sufficient evidence (3 unrelated cases and functional studies) for this gene to be promoted to GREEN at the next major review.
Hereditary neuropathy or pain disorder v3.15 DRP2 Achchuthan Shanmugasundram Gene: drp2 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v3.14 DRP2 Achchuthan Shanmugasundram Publications for gene: DRP2 were set to 26227883; 29473052
Hereditary neuropathy or pain disorder v3.13 DRP2 Achchuthan Shanmugasundram reviewed gene: DRP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22764250, 26227883, 29473052, 31217940; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Congenital myopathy v4.29 TRDN Achchuthan Shanmugasundram Tag Q2_23_NHS_review tag was added to gene: TRDN.
Congenital myopathy v4.29 TRDN Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: TRDN.
Congenital myopathy v4.29 TRDN Achchuthan Shanmugasundram Classified gene: TRDN as Amber List (moderate evidence)
Congenital myopathy v4.29 TRDN Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Anna Sarkozy (Great Ormond Street Hospital), there is sufficient evidence (9 unrelated cases) for promoting this gene to Green at the next major review.
Congenital myopathy v4.29 TRDN Achchuthan Shanmugasundram Gene: trdn has been classified as Amber List (Moderate Evidence).
Congenital myopathy v4.28 TRDN Achchuthan Shanmugasundram Publications for gene: TRDN were set to 25922419; 28202702
Congenital myopathy v4.27 TRDN Achchuthan Shanmugasundram reviewed gene: TRDN: Rating: GREEN; Mode of pathogenicity: None; Publications: 25922419, 28202702, 30649896; Phenotypes: Cardiac arrhythmia syndrome, with or without skeletal muscle weakness, OMIM:615441; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital myopathy v4.27 ZC4H2 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Anna Sarkozy (Great Ormond Street Hospital) and others, variants in ZC4H2 cause a clinical phenotype that includes congenital arthrogryposis, joint contractures and muscle weakness similar to that has been seen in structural myopathies. As there is sufficient number of cases, this gene can be promoted to green at the next major review.; to: Comment on list classification: As reviewed by Anna Sarkozy (Great Ormond Street Hospital) and others, variants in ZC4H2 cause a clinical phenotype that includes congenital arthrogryposis, joint contractures and muscle weakness similar to what has been seen in structural myopathies. As there is sufficient number of cases, this gene can be promoted to green at the next major review.
Congenital myopathy v4.27 ZC4H2 Achchuthan Shanmugasundram Tag Q2_23_NHS_review tag was added to gene: ZC4H2.
Congenital myopathy v4.27 ZC4H2 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: ZC4H2.
Congenital myopathy v4.27 ZC4H2 Achchuthan Shanmugasundram Classified gene: ZC4H2 as Amber List (moderate evidence)
Congenital myopathy v4.27 ZC4H2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Anna Sarkozy (Great Ormond Street Hospital) and others, variants in ZC4H2 cause a clinical phenotype that includes congenital arthrogryposis, joint contractures and muscle weakness similar to that has been seen in structural myopathies. As there is sufficient number of cases, this gene can be promoted to green at the next major review.
Congenital myopathy v4.27 ZC4H2 Achchuthan Shanmugasundram Gene: zc4h2 has been classified as Amber List (Moderate Evidence).
Congenital myopathy v4.26 ZC4H2 Achchuthan Shanmugasundram reviewed gene: ZC4H2: Rating: AMBER; 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)
Arthrogryposis v5.4 SVIL Tracy Lester gene: SVIL was added
gene: SVIL was added to Arthrogryposis. Sources: NHS GMS
Mode of inheritance for gene: SVIL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SVIL were set to 32779703
Phenotypes for gene: SVIL were set to myopathy; contractures; raised CK
Penetrance for gene: SVIL were set to unknown
Review for gene: SVIL was set to AMBER
Added comment: Four individuals from two unrelated consanguineous families with a childhood/adolescence onset of a myopathy associated with homozygous loss-of-function mutations in SVIL. Wide neck, anteverted shoulders and prominent trapezius muscles together with variable contractures were characteristic features. Functional studies on muscle biopsies showed complete loss protein in muscle fibres by western blot.
Sources: Literature
Sources: NHS GMS
Congenital myopathy v4.26 ACTN2 Achchuthan Shanmugasundram reviewed gene: ACTN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30701273; Phenotypes: Congenital myopathy 8, OMIM:618654; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.11 ACTN2 Achchuthan Shanmugasundram changed review comment from: Comment on mode of inheritance: There are at least 8 unrelated cases with monoallelic inheritance reported in literature.

Although there are three unrelated Japanese cases with biallelic inheritance reported in PMID:34471957, all of them were identified with the same homozygous variant.

Hence, 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' has currently been chosen as the MOI and it will be reviewed when more cases are reported with biallelic inheritance.; to: Comment on mode of inheritance: There are at least 8 unrelated cases with monoallelic inheritance reported in literature.

Although there are three unrelated Japanese cases with biallelic inheritance reported in PMID:34471957, all of them were identified with the same homozygous variant.

'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' has currently been chosen as the MOI and it will be reviewed when more cases are reported with biallelic inheritance. Hence, 'watchlist_moi' tag has been added.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.11 ACTN2 Achchuthan Shanmugasundram Tag watchlist_moi tag was added to gene: ACTN2.
Congenital myopathy v4.26 TNNI2 Achchuthan Shanmugasundram reviewed gene: TNNI2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Congenital myopathy v4.26 ECEL1 Achchuthan Shanmugasundram reviewed gene: ECEL1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Congenital myopathy v4.26 ADSSL1 Achchuthan Shanmugasundram edited their review of gene: ADSSL1: Changed rating: GREEN
Intellectual disability v5.67 PLK1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.67 PLK1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.67 PLK1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.67 TAF2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.67 TAF2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.67 GRIA1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.67 GRIA1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.67 GRIA1 Achchuthan Shanmugasundram changed review comment from: Four different heterozygous variants in GRIA1 (p.Ala636Thr, p.Gly745Asp, p.Ile627Thr & p.Arg345Gln) have been identified in six unrelated individuals and they were all reported with intellectual disability, moderate to severe cognitive impairment, delayed motor development, speech impairment and behavioural issues such as anxiety, autism spectrum disorder and attention deficit hyperactivity disorder.

Homozygous variant (p.Arg377Ter) has been identified in one individual, who presented with intellectual disability, severe cognitive impairment, delayed motor development, speech impairment (non-verbal) and self-injurious behaviour.

In vitro functional studies with major GluA1-containing AMPAR subtypes carrying the GRIA1 variant mutations showed that three of the four missense variants profoundly perturb receptor function. The homozygous stop-gain variant completely destroyed the expression of GluA1-containing AMPARs. The Xenopus gria1 models also show transient motor deficits, an intermittent seizure phenotype, and a significant impairment to working memory in mutants.; to: Four different heterozygous variants in GRIA1 (p.Ala636Thr, p.Gly745Asp, p.Ile627Thr & p.Arg345Gln) have been identified in six unrelated individuals and they were all reported with intellectual disability, moderate to severe cognitive impairment, delayed motor development, speech impairment and behavioural issues such as anxiety, autism spectrum disorder and attention deficit hyperactivity disorder.

Homozygous variant (p.Arg377Ter) has been identified in one individual, who presented with intellectual disability, severe cognitive impairment, delayed motor development, speech impairment (non-verbal) and self-injurious behaviour.

In vitro functional studies with major GluA1-containing AMPAR subtypes carrying the GRIA1 variant mutations showed that three of the four missense variants profoundly perturb receptor function. The homozygous stop-gain variant completely destroyed the expression of GluA1-containing AMPARs. The Xenopus gria1 models also show transient motor deficits, an intermittent seizure phenotype, and a significant impairment to working memory in mutants.

This gene has also been associated with relevant phenotypes in both OMIM (MIM #619927 & MIM #619931) and Gene2Phenotype (with 'moderate' rating).
Intellectual disability v5.67 GRIA1 Achchuthan Shanmugasundram Classified gene: GRIA1 as Amber List (moderate evidence)
Intellectual disability v5.67 GRIA1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (6 unrelated cases with monoallelic inheritance and functional evidence including Xenopus models) for this gene to be promoted to GREEN at the next major review.
Intellectual disability v5.67 GRIA1 Achchuthan Shanmugasundram Gene: gria1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.67 GRIA1 Achchuthan Shanmugasundram Classified gene: GRIA1 as Amber List (moderate evidence)
Intellectual disability v5.67 GRIA1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (6 unrelated cases with monoallelic inheritance and functional evidence including Xenopus models) for this gene to be promoted to GREEN at the next major review.
Intellectual disability v5.67 GRIA1 Achchuthan Shanmugasundram Gene: gria1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.66 GRIA1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.66 GRIA1 Achchuthan Shanmugasundram Classified gene: GRIA1 as Amber List (moderate evidence)
Intellectual disability v5.66 GRIA1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (6 unrelated cases with monoallelic inheritance and functional evidence including Xenopus models) for this gene to be promoted to GREEN at the next major review.
Intellectual disability v5.66 GRIA1 Achchuthan Shanmugasundram Gene: gria1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.66 GRIA1 Achchuthan Shanmugasundram Classified gene: GRIA1 as Amber List (moderate evidence)
Intellectual disability v5.66 GRIA1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (6 unrelated cases with monoallelic inheritance and functional evidence including Xenopus models) for this gene to be promoted to GREEN at the next major review.
Intellectual disability v5.66 GRIA1 Achchuthan Shanmugasundram Gene: gria1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.65 GRIA1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.65 GRIA1 Achchuthan Shanmugasundram Phenotypes for gene: GRIA1 were changed from Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931 to Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931
Intellectual disability v5.63 GRIA1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.63 GRIA1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.63 GRIA1 Achchuthan Shanmugasundram Phenotypes for gene: GRIA1 were changed from Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931 to Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931
Intellectual disability v5.65 GRIA1 Achchuthan Shanmugasundram Phenotypes for gene: GRIA1 were changed from Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931 to Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931
Intellectual disability v5.64 GRIA1 Achchuthan Shanmugasundram Phenotypes for gene: GRIA1 were changed from Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931 to Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931
Intellectual disability v5.65 GRIA1 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: The MOI should be monoallelic, as there is only one case identified with biallelic inheritance.
Intellectual disability v5.65 GRIA1 Achchuthan Shanmugasundram Mode of inheritance for gene: GRIA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.63 GRIA1 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: The MOI should be monoallelic, as there is only one case identified with biallelic inheritance.
Intellectual disability v5.63 GRIA1 Achchuthan Shanmugasundram Mode of inheritance for gene: GRIA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.64 GRIA1 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: The MOI should be monoallelic, as there is only one case identified with biallelic inheritance.
Intellectual disability v5.64 GRIA1 Achchuthan Shanmugasundram Mode of inheritance for gene: GRIA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.64 GRIA1 Achchuthan Shanmugasundram Tag watchlist was removed from gene: GRIA1.
Tag Q2_23_promote_green tag was added to gene: GRIA1.
Intellectual disability v5.64 GRIA1 Achchuthan Shanmugasundram Phenotypes for gene: GRIA1 were changed from Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931 to Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931
Intellectual disability v5.63 GRIA1 Achchuthan Shanmugasundram Publications for gene: GRIA1 were set to 28628100; 23033978; 26350204; 24896178; 35675825
Intellectual disability v5.63 GRIA1 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: The MOI should be monoallelic, as there is only one case identified with biallelic inheritance.
Intellectual disability v5.63 GRIA1 Achchuthan Shanmugasundram Mode of inheritance for gene: GRIA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.64 GRIA1 Achchuthan Shanmugasundram Phenotypes for gene: GRIA1 were changed from Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931 to Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931
Intellectual disability v5.63 GRIA1 Achchuthan Shanmugasundram Phenotypes for gene: GRIA1 were changed from Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931 to Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931
Intellectual disability v5.63 GRIA1 Achchuthan Shanmugasundram Phenotypes for gene: GRIA1 were changed from Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931 to Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931
Intellectual disability v5.62 GRIA1 Achchuthan Shanmugasundram Publications for gene: GRIA1 were set to 28628100; 23033978; 26350204; 24896178; 35675825
Intellectual disability v5.63 GRIA1 Achchuthan Shanmugasundram Phenotypes for gene: GRIA1 were changed from Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931 to Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931
Intellectual disability v5.63 GRIA1 Achchuthan Shanmugasundram Phenotypes for gene: GRIA1 were changed from Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931 to Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931
Intellectual disability v5.63 GRIA1 Achchuthan Shanmugasundram Phenotypes for gene: GRIA1 were changed from Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931 to Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931
Intellectual disability v5.63 GRIA1 Achchuthan Shanmugasundram Phenotypes for gene: GRIA1 were changed from Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931 to Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931
Intellectual disability v5.63 GRIA1 Achchuthan Shanmugasundram Phenotypes for gene: GRIA1 were changed from Intellectual disability to Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931
Intellectual disability v5.62 GRIA1 Achchuthan Shanmugasundram Publications for gene: GRIA1 were set to 28628100; 23033978; 26350204; 24896178; 35675825
Intellectual disability v5.63 GRIA1 Achchuthan Shanmugasundram Publications for gene: GRIA1 were set to 28628100; 23033978; 26350204; 24896178; 35675825
Intellectual disability v5.62 GRIA1 Achchuthan Shanmugasundram Publications for gene: GRIA1 were set to 28628100; 23033978; 26350204; 24896178; 35675825
Intellectual disability v5.62 GRIA1 Achchuthan Shanmugasundram Publications for gene: GRIA1 were set to 28628100; 23033978; 26350204; 24896178; 35675825
Intellectual disability v5.62 GRIA1 Achchuthan Shanmugasundram Publications for gene: GRIA1 were set to 28628100; 23033978; 26350204; 24896178
Intellectual disability v5.61 GRIA1 Achchuthan Shanmugasundram reviewed gene: GRIA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35675825; Phenotypes: Intellectual developmental disorder, autosomal dominant 67, OMIM:619927, ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia and cerebellar anomalies - narrow panel v4.7 PRDX3 Achchuthan Shanmugasundram changed review comment from: Comment on publications: PMID:35766882 reports a case of infantile-onset cerebellar ataxia that started ate 19 months old and presented with severe cerebellar atrophy and peripheral neuropathy early in the course of disease. This patient was identified with the homozygous variant p.Asp163Glu in PRDX3 gene.; to: Comment on publications: PMID:35766882 reports a case of infantile-onset cerebellar ataxia that started at the age of 19 months and presented with severe cerebellar atrophy and peripheral neuropathy early in the course of disease. This patient was identified with the homozygous variant p.Asp163Glu in PRDX3 gene.
Neurological ciliopathies v3.10 CCDC28B Sarah Leigh changed review comment from: Not associated with a Joubert syndrome phenotype in OMIM, Gen2Phen or MONDO. PMID: 32139166 reports one homozygous CCDC28B variant (rs1407134) in a child with features of Joubert syndrome - polydactyly, severe intellectual disability and molar tooth sign in brain imaging. The fetal sibbling of this child (terminated) was also homozygous for this variant. The allele frequency of rs1407134 (gnomAD Exomes (V 2.1.1) ƒ = 0.0326) makes it unlikely to be disease causing.
PMID: 23727834 demonstrates that CCDC28B is involved in the control of cilial length.; to: Not associated with a Joubert syndrome phenotype in OMIM, Gen2Phen or MONDO. PMID: 32139166 reports one homozygous CCDC28B variant (rs1407134) in a child with features of Joubert syndrome - polydactyly, severe intellectual disability and molar tooth sign in brain imaging. The fetal sibbling of this child (terminated) was also homozygous for this variant. The allele frequency of rs1407134 (gnomAD Exomes (V 2.1.1) ƒ = 0.0326) makes it unlikely to be disease causing, plus, it is classified as Benign in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/1271446/).
PMID: 23727834 demonstrates that CCDC28B is involved in the control of cilial length.
Neurological ciliopathies v3.10 CCDC28B Sarah Leigh reviewed gene: CCDC28B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Neurological ciliopathies v3.10 CCDC28B Sarah Leigh Publications for gene: CCDC28B were set to 32139166
Neurological ciliopathies v3.9 CCDC28B Sarah Leigh Classified gene: CCDC28B as Red List (low evidence)
Neurological ciliopathies v3.9 CCDC28B Sarah Leigh Gene: ccdc28b has been classified as Red List (Low Evidence).
Neurological ciliopathies v3.8 CCDC28B Sarah Leigh Phenotypes for gene: CCDC28B were changed from Joubert syndrome to Joubert syndrome, MONDO:0018772
Neurological ciliopathies v3.7 CCDC28B Sarah Leigh Classified gene: CCDC28B as Amber List (moderate evidence)
Neurological ciliopathies v3.7 CCDC28B Sarah Leigh Gene: ccdc28b has been classified as Amber List (Moderate Evidence).
Neurological ciliopathies v3.6 TOGARAM1 Sarah Leigh Tag Q2_23_promote_green tag was added to gene: TOGARAM1.
Neurological ciliopathies v3.6 TOGARAM1 Sarah Leigh edited their review of gene: TOGARAM1: Added comment: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. PMIDs:32747439; 32453716 report seven TOGARAM1 variants in five unrelated cases of Joubert syndrome 37, OMIM:619185. Supportive functional datawas presented PMIDs:32747439; 32453716.; Changed rating: GREEN
Neurological ciliopathies v3.6 TOGARAM1 Sarah Leigh Classified gene: TOGARAM1 as Amber List (moderate evidence)
Neurological ciliopathies v3.6 TOGARAM1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Neurological ciliopathies v3.6 TOGARAM1 Sarah Leigh Gene: togaram1 has been classified as Amber List (Moderate Evidence).
Neurological ciliopathies v3.5 TOGARAM1 Sarah Leigh Phenotypes for gene: TOGARAM1 were changed from Joubert syndrome 37, MIM# 619185 to Joubert syndrome 37, OMIM:619185; Joubert syndrome 37, MONDO:0030933
Neurological ciliopathies v3.4 IFT74 Sarah Leigh edited their review of gene: IFT74: Added comment: Associated with Joubert syndrome 40 in OMIM (OMIM:619582) and as a definitive gene for IFT74-associated ciliopathy in Gen2Phen. Five IFT74 variants have been associated with OMIM:619582, in four unrelated Chinese families, supportive functional studies have been perfomed on patient fibroblasts and zebra fish IFT74 morphants (PMID: 33531668).; Changed rating: GREEN
Neurological ciliopathies v3.4 IFT74 Sarah Leigh Tag Q2_23_promote_green tag was added to gene: IFT74.
Neurological ciliopathies v3.4 IFT74 Sarah Leigh Classified gene: IFT74 as Amber List (moderate evidence)
Neurological ciliopathies v3.4 IFT74 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Neurological ciliopathies v3.4 IFT74 Sarah Leigh Gene: ift74 has been classified as Amber List (Moderate Evidence).
Neurological ciliopathies v3.3 IFT74 Sarah Leigh Phenotypes for gene: IFT74 were changed from Joubert syndrome to Joubert syndrome 40, OMIM:619582; Joubert syndrome 40, MONDO:0030462
Neurological ciliopathies v3.2 CBY1 Sarah Leigh Tag Q2_23_promote_green tag was added to gene: CBY1.
Neurological ciliopathies v3.2 CBY1 Sarah Leigh edited their review of gene: CBY1: Added comment: Not associated with a phenotype in OMIM, Gen2Phen or MONDO. PMID: 33131181 reports two frame shifting CBY1 variants ( NM_015373.3:c.189_190del; p.(Val65*) & NM_015373.3:c.64_65dup; p.(Asn23Profs*24)), one in each of two consanguineous families, where the parents were heterozygous and the affected children were homozygous. Extensive functional studies have shown the role of CBY1 in cilial formation and function, and the disruptive effect of the variants (PMID: 33131181; 25103236; 25220153).; Changed rating: GREEN
Neurological ciliopathies v3.2 CBY1 Sarah Leigh Classified gene: CBY1 as Amber List (moderate evidence)
Neurological ciliopathies v3.2 CBY1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Neurological ciliopathies v3.2 CBY1 Sarah Leigh Gene: cby1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v3.3 KIF21A Arina Puzriakova Publications for gene: KIF21A were set to 34740919
Fetal anomalies v3.2 KIF21A Arina Puzriakova Classified gene: KIF21A as Amber List (moderate evidence)
Fetal anomalies v3.2 KIF21A Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to recommend this gene to NHS GMS for promoting to green rating.

There are two unrelated families with homozygous loss of function variants in KIF21A were reported with severe fetal akinesia with arthrogryposis multiplex in PMID:34740919. Hannah Robinson (South West Genomic Laboratory Hub) reported an additional case identified in Exeter Genomics Laboratory exhibiting homozygous nonsense variant in KIF21A and was diagnosed with arthrogryposis.

In addition, PMID:32686171 reports overlapping phenotypes observed in KIF21A null piglets, where a 63-bp insertion in exon 2 of the porcine KIF21A gene is associated with arthrogryposis multiplex congenita.
Fetal anomalies v3.2 KIF21A Arina Puzriakova Gene: kif21a has been classified as Amber List (Moderate Evidence).
Fetal anomalies v3.1 KIF21A Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: KIF21A.
Tag Q2_23_NHS_review tag was added to gene: KIF21A.
Arthrogryposis v5.4 KIF21A Arina Puzriakova Tag Q1_23_NHS_review tag was added to gene: KIF21A.
Adult onset neurodegenerative disorder v4.22 PSAP Sarah Leigh Tag Q2_23_promote_green tag was added to gene: PSAP.
Adult onset neurodegenerative disorder v4.22 PSAP Sarah Leigh edited their review of gene: PSAP: Added comment: Associated with Parkinson disease 24, autosomal dominant, susceptibility to (OMIM:619491), but not associated with the same condition in Gen2Phen. PMID: 32201884 reports three PSAP variants in three unrelated families with OMIM:619491. Supportive in vitro functional studies were also presented for the reported variants. However, it would appear that there maybe variable expressivity or incomplete penetrance of the Parkinson phenotype, as two variant carrying sibs in Family 2 had extrapyramidal signs, but did not have the full Parkinsons phenotype (PMID: 32201884).; Changed rating: GREEN
Adult onset neurodegenerative disorder v4.22 PSAP Sarah Leigh Classified gene: PSAP as Amber List (moderate evidence)
Adult onset neurodegenerative disorder v4.22 PSAP Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Adult onset neurodegenerative disorder v4.22 PSAP Sarah Leigh Gene: psap has been classified as Amber List (Moderate Evidence).
Adult onset neurodegenerative disorder v4.21 PSAP Sarah Leigh Phenotypes for gene: PSAP were changed from Parkinson disease, AD to {Parkinson disease 24, autosomal dominant, susceptibility to}, OMIM:619491
Adult onset neurodegenerative disorder v4.20 GLT8D1 Sarah Leigh reviewed gene: GLT8D1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Adult onset neurodegenerative disorder v4.20 GLT8D1 Sarah Leigh Classified gene: GLT8D1 as Amber List (moderate evidence)
Adult onset neurodegenerative disorder v4.20 GLT8D1 Sarah Leigh Gene: glt8d1 has been classified as Amber List (Moderate Evidence).
Adult onset neurodegenerative disorder v4.19 GLT8D1 Sarah Leigh Publications for gene: GLT8D1 were set to 30811981; 35525134:33581933:31653410:33714647:34746377
Adult onset neurodegenerative disorder v4.18 GLT8D1 Sarah Leigh Phenotypes for gene: GLT8D1 were changed from Amyotrophic lateral sclerosis to familial amyotrophic lateral sclerosis, MONDO:0005144
Adult onset neurodegenerative disorder v4.17 GLT8D1 Sarah Leigh Publications for gene: GLT8D1 were set to 30811981
White matter disorders and cerebral calcification - narrow panel v3.8 C2orf69 Arina Puzriakova Entity copied from Mitochondrial disorders v4.27
White matter disorders and cerebral calcification - narrow panel v3.8 C2orf69 Arina Puzriakova gene: C2orf69 was added
gene: C2orf69 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Amber,Literature
Q2_23_promote_green tags were added to gene: C2orf69.
Mode of inheritance for gene: C2orf69 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C2orf69 were set to 34038740; 33945503
Phenotypes for gene: C2orf69 were set to Combined oxidative phosphorylation deficiency 53, OMIM:619423
Intellectual disability v5.61 C2orf69 Arina Puzriakova Entity copied from Mitochondrial disorders v4.27
Intellectual disability v5.61 C2orf69 Arina Puzriakova gene: C2orf69 was added
gene: C2orf69 was added to Intellectual disability - microarray and sequencing. Sources: Expert Review Amber,Literature
Q2_23_promote_green tags were added to gene: C2orf69.
Mode of inheritance for gene: C2orf69 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C2orf69 were set to 34038740; 33945503
Phenotypes for gene: C2orf69 were set to Combined oxidative phosphorylation deficiency 53, OMIM:619423
Possible mitochondrial disorder - nuclear genes v3.27 C2orf69 Arina Puzriakova Entity copied from Mitochondrial disorders v4.27
Possible mitochondrial disorder - nuclear genes v3.27 C2orf69 Arina Puzriakova gene: C2orf69 was added
gene: C2orf69 was added to Possible mitochondrial disorder - nuclear genes. Sources: Expert Review Amber,Literature
Q2_23_promote_green tags were added to gene: C2orf69.
Mode of inheritance for gene: C2orf69 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C2orf69 were set to 34038740; 33945503
Phenotypes for gene: C2orf69 were set to Combined oxidative phosphorylation deficiency 53, OMIM:619423
Early onset or syndromic epilepsy v4.18 C2orf69 Arina Puzriakova Entity copied from Mitochondrial disorders v4.27
Early onset or syndromic epilepsy v4.18 C2orf69 Arina Puzriakova gene: C2orf69 was added
gene: C2orf69 was added to Early onset or syndromic epilepsy. Sources: Expert Review Amber,Literature
Q2_23_promote_green tags were added to gene: C2orf69.
Mode of inheritance for gene: C2orf69 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C2orf69 were set to 34038740; 33945503
Phenotypes for gene: C2orf69 were set to Combined oxidative phosphorylation deficiency 53, OMIM:619423
Mitochondrial disorders v4.27 C2orf69 Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: C2orf69.
Mitochondrial disorders v4.27 C2orf69 Arina Puzriakova Classified gene: C2orf69 as Amber List (moderate evidence)
Mitochondrial disorders v4.27 C2orf69 Arina Puzriakova Added comment: Comment on list classification: New gene added to this panel by Zornitza Stark (Australian Genomics). Associated with a relevant phenotype in OMIM (MIM# 619423) but is not yet listed in G2P. At least 13 unrelated families reported in literature (PMIDs: 33945503; 34038740). Sufficient cases plus zebrafish model to promote this gene to green at the next GMS panel update.
Mitochondrial disorders v4.27 C2orf69 Arina Puzriakova Gene: c2orf69 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.6 C2orf69 Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: C2orf69.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.6 C2orf69 Arina Puzriakova Classified gene: C2orf69 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.6 C2orf69 Arina Puzriakova Added comment: Comment on list classification: New gene added to this panel by Boaz Palterer (University of Florence). Associated with a relevant phenotype in OMIM (MIM# 619423) but is not yet listed in G2P. At least 13 unrelated families reported in literature (PMIDs: 33945503; 34038740). Sufficient cases plus zebrafish model to promote this gene to green at the next GMS panel update.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.6 C2orf69 Arina Puzriakova Gene: c2orf69 has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v4.26 C2orf69 Arina Puzriakova Phenotypes for gene: C2orf69 were changed from Combined oxidative phosphorylation deficiency-53 (COXPD53), MIM#619423 to Combined oxidative phosphorylation deficiency 53, OMIM:619423
Primary immunodeficiency or monogenic inflammatory bowel disease v4.5 C2orf69 Arina Puzriakova Phenotypes for gene: C2orf69 were changed from hypomyelination; microcephaly; liver dysfunction; autoinflammation; leukoencephalopathy to Combined oxidative phosphorylation deficiency 53, OMIM:619423
Primary immunodeficiency or monogenic inflammatory bowel disease v4.4 ATAD3A Arina Puzriakova Classified gene: ATAD3A as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.4 ATAD3A Arina Puzriakova Added comment: Comment on list classification: New gene added to this panel by Boaz Palterer (University of Florence). Although the Lepelley et al. 2021 (PMID: 34387651) paper described multiple patients with interferon signalling disturbances it does not appear likely that this would form the basis for diagnostic testing in a clinical setting. ATAD3A is associated with a wide spectrum of clinical features but immune phenotypes do not appear particularly prominent. However, as two patients in PMID: 34387651 did demonstrate signs consistent with standardised criteria for a diagnosis of the autoimmune disorder systemic sclerosis, rating Amber for now awaiting further evidence supporting inclusion on this panel.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.4 ATAD3A Arina Puzriakova Gene: atad3a has been classified as Amber List (Moderate Evidence).
Childhood onset hereditary spastic paraplegia v4.6 ATAD3A Arina Puzriakova Publications for gene: ATAD3A were set to 28158749
Childhood onset hereditary spastic paraplegia v4.5 ATAD3A Arina Puzriakova Classified gene: ATAD3A as Amber List (moderate evidence)
Childhood onset hereditary spastic paraplegia v4.5 ATAD3A Arina Puzriakova Gene: atad3a has been classified as Amber List (Moderate Evidence).
Childhood onset hereditary spastic paraplegia v4.4 ATAD3A Arina Puzriakova edited their review of gene: ATAD3A: Added comment: PMID: 34387651 - one patient with spastic diplegic gait that appeared stable since early infancy, harbouring the same p.(Gly355Asp) variant in ATAD3A as seen in the patient previously reported by Cooper et al. 2017 (PMID: 28158749). This is the second case where the early phenotype was notable for spasticity in early childhood and therefore upgrading the rating from Red to Amber.; Changed publications to: 28158749, 27640307, 33845882, 34387651; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Adult onset neurodegenerative disorder v4.16 DNAJB2 Sarah Leigh Tag Q2_23_promote_green tag was added to gene: DNAJB2.
Adult onset neurodegenerative disorder v4.16 DNAJB2 Sarah Leigh edited their review of gene: DNAJB2: Added comment: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least three variants have been reported in three unrelated cases (PMID: 22522442, 25274842).; Changed rating: GREEN
Adult onset neurodegenerative disorder v4.16 DNAJB2 Sarah Leigh Classified gene: DNAJB2 as Amber List (moderate evidence)
Adult onset neurodegenerative disorder v4.16 DNAJB2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Adult onset neurodegenerative disorder v4.16 DNAJB2 Sarah Leigh Gene: dnajb2 has been classified as Amber List (Moderate Evidence).
Adult onset neurodegenerative disorder v4.15 DNAJB2 Sarah Leigh Publications for gene: DNAJB2 were set to
Adult onset neurodegenerative disorder v4.14 DNAJB2 Sarah Leigh Phenotypes for gene: DNAJB2 were changed from Spinal muscular atrophy, distal, autosomal recessive, 5, 614881 to Spinal muscular atrophy, distal, autosomal recessive, 5, OMIM:614881; young adult-onset distal hereditary motor neuropathy, MONDO:0013947
Intellectual disability v5.60 TAF2 Achchuthan Shanmugasundram Classified gene: TAF2 as Amber List (moderate evidence)
Intellectual disability v5.60 TAF2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (at least 4 unrelated cases) for this gene to be promoted to GREEN at the next major review.
Intellectual disability v5.60 TAF2 Achchuthan Shanmugasundram Gene: taf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.60 TAF2 Achchuthan Shanmugasundram Classified gene: TAF2 as Amber List (moderate evidence)
Intellectual disability v5.60 TAF2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (at least 4 unrelated cases) for this gene to be promoted to GREEN at the next major review.
Intellectual disability v5.60 TAF2 Achchuthan Shanmugasundram Gene: taf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.59 TAF2 Achchuthan Shanmugasundram Publications for gene: TAF2 were set to 21937992; 22633631; 24084144; 26350204; 34474177
Intellectual disability v5.59 TAF2 Achchuthan Shanmugasundram Publications for gene: TAF2 were set to 21937992; 22633631; 24084144; 26350204; 34474177
Intellectual disability v5.58 TAF2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.58 TAF2 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: TAF2.
Intellectual disability v5.58 TAF2 Achchuthan Shanmugasundram Publications for gene: TAF2 were set to 21937992; 22633631; 24084144; 26350204; 34474177
Intellectual disability v5.60 TAF2 Achchuthan Shanmugasundram Classified gene: TAF2 as Amber List (moderate evidence)
Intellectual disability v5.60 TAF2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (at least 4 unrelated cases) for this gene to be promoted to GREEN at the next major review.
Intellectual disability v5.60 TAF2 Achchuthan Shanmugasundram Gene: taf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.60 TAF2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.60 TAF2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.60 TAF2 Achchuthan Shanmugasundram Classified gene: TAF2 as Amber List (moderate evidence)
Intellectual disability v5.60 TAF2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (at least 4 unrelated cases) for this gene to be promoted to GREEN at the next major review.
Intellectual disability v5.60 TAF2 Achchuthan Shanmugasundram Gene: taf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.60 TAF2 Achchuthan Shanmugasundram Classified gene: TAF2 as Amber List (moderate evidence)
Intellectual disability v5.60 TAF2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (at least 4 unrelated cases) for this gene to be promoted to GREEN at the next major review.
Intellectual disability v5.60 TAF2 Achchuthan Shanmugasundram Gene: taf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.59 TAF2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.59 TAF2 Achchuthan Shanmugasundram Classified gene: TAF2 as Amber List (moderate evidence)
Intellectual disability v5.59 TAF2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (at least 4 unrelated cases) for this gene to be promoted to GREEN at the next major review.
Intellectual disability v5.59 TAF2 Achchuthan Shanmugasundram Gene: taf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.59 TAF2 Achchuthan Shanmugasundram Classified gene: TAF2 as Amber List (moderate evidence)
Intellectual disability v5.59 TAF2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (at least 4 unrelated cases) for this gene to be promoted to GREEN at the next major review.
Intellectual disability v5.59 TAF2 Achchuthan Shanmugasundram Gene: taf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.59 TAF2 Achchuthan Shanmugasundram Publications for gene: TAF2 were set to 21937992; 22633631; 24084144; 26350204; 34474177
Intellectual disability v5.59 TAF2 Achchuthan Shanmugasundram Publications for gene: TAF2 were set to 21937992; 22633631; 24084144; 26350204; 34474177
Intellectual disability v5.58 TAF2 Achchuthan Shanmugasundram Publications for gene: TAF2 were set to 21937992; 22633631; 24084144; 26350204; 34474177
Intellectual disability v5.58 TAF2 Achchuthan Shanmugasundram Publications for gene: TAF2 were set to 21937992; 22633631; 24084144; 26350204; 34474177
Intellectual disability v5.58 TAF2 Achchuthan Shanmugasundram Publications for gene: TAF2 were set to 21937992; 22633631; 24084144; 26350204; 34474177
Intellectual disability v5.58 TAF2 Achchuthan Shanmugasundram Publications for gene: TAF2 were set to 21937992; 24084144; 26350204
Intellectual disability v5.57 TAF2 Achchuthan Shanmugasundram reviewed gene: TAF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 21937992, 24084144, 34474177; Phenotypes: Mental retardation, autosomal recessive 40, OMIM:615599; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.57 SHANK1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.57 SHANK1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: SHANK1.
Intellectual disability v5.57 SHANK1 Achchuthan Shanmugasundram Classified gene: SHANK1 as Amber List (moderate evidence)
Intellectual disability v5.57 SHANK1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (at least four unrelated cases) for this gene to be promoted to GREEN at the next major review.
Intellectual disability v5.57 SHANK1 Achchuthan Shanmugasundram Gene: shank1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.57 SHANK1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.57 SHANK1 Achchuthan Shanmugasundram Classified gene: SHANK1 as Amber List (moderate evidence)
Intellectual disability v5.57 SHANK1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (at least four unrelated cases) for this gene to be promoted to GREEN at the next major review.
Intellectual disability v5.57 SHANK1 Achchuthan Shanmugasundram Gene: shank1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.56 SHANK1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.56 SHANK1 Achchuthan Shanmugasundram Classified gene: SHANK1 as Amber List (moderate evidence)
Intellectual disability v5.56 SHANK1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (at least four unrelated cases) for this gene to be promoted to GREEN at the next major review.
Intellectual disability v5.56 SHANK1 Achchuthan Shanmugasundram Gene: shank1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.56 SHANK1 Achchuthan Shanmugasundram Classified gene: SHANK1 as Amber List (moderate evidence)
Intellectual disability v5.56 SHANK1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (at least four unrelated cases) for this gene to be promoted to GREEN at the next major review.
Intellectual disability v5.56 SHANK1 Achchuthan Shanmugasundram Gene: shank1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.55 SHANK1 Achchuthan Shanmugasundram Phenotypes for gene: SHANK1 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.55 SHANK1 Achchuthan Shanmugasundram Phenotypes for gene: SHANK1 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.55 SHANK1 Achchuthan Shanmugasundram Phenotypes for gene: SHANK1 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.55 SHANK1 Achchuthan Shanmugasundram Phenotypes for gene: SHANK1 were changed from AUTISM to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.54 SHANK1 Achchuthan Shanmugasundram changed review comment from: As reviewed by Zornitza Stark (Australian Genomics), PMID:34113010 reported six individuals who presented with neurodevelopmental disorders and identified with de novo truncating variants in SHANK1 gene. Of these six individuals, four had intellectual disability, one had severe learning difficulties and one with auditory processing disorder, difficulty with executive functioning, mathematic concepts, verbal reasoning and problem solving.; to: As reviewed by Zornitza Stark (Australian Genomics), PMID:34113010 reported six unrelated individuals who presented with neurodevelopmental disorders and identified with de novo truncating variants in SHANK1 gene. Of these six individuals, four had intellectual disability, one had severe learning difficulties and one with auditory processing disorder, difficulty with executive functioning, mathematic concepts, verbal reasoning and problem solving. Three of these patients were also reported with autism spectrum disorder.

This gene has been associated with relevant phenotypes in Gene2Phenotype (with 'strong' rating in the DD panel).
Intellectual disability v5.54 SHANK1 Achchuthan Shanmugasundram Publications for gene: SHANK1 were set to 0
Intellectual disability v5.53 SHANK1 Achchuthan Shanmugasundram edited their review of gene: SHANK1: Changed phenotypes to: neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071
Intellectual disability v5.53 SHANK1 Achchuthan Shanmugasundram edited their review of gene: SHANK1: Added comment: As reviewed by Zornitza Stark (Australian Genomics), PMID:34113010 reported six individuals who presented with neurodevelopmental disorders and identified with de novo truncating variants in SHANK1 gene. Of these six individuals, four had intellectual disability, one had severe learning difficulties and one with auditory processing disorder, difficulty with executive functioning, mathematic concepts, verbal reasoning and problem solving.; Changed phenotypes to: nearodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071
Intellectual disability v5.53 SHANK1 Achchuthan Shanmugasundram reviewed gene: SHANK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34113010; Phenotypes: neurocde; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Severe early-onset obesity v4.3 DYRK1B Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: DYRK1B.
Tag Q2_23_NHS_review tag was added to gene: DYRK1B.
Severe early-onset obesity v4.3 DYRK1B Achchuthan Shanmugasundram Classified gene: DYRK1B as Amber List (moderate evidence)
Severe early-onset obesity v4.3 DYRK1B Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Tracy Lester (Genetics laboratory, Oxford UK), there is sufficient evidence (>10 unrelated cases) available in support of promoting this gene to GREEN rating at the next major review.
Severe early-onset obesity v4.3 DYRK1B Achchuthan Shanmugasundram Gene: dyrk1b has been classified as Amber List (Moderate Evidence).
Severe early-onset obesity v4.2 DYRK1B Achchuthan Shanmugasundram Phenotypes for gene: DYRK1B were changed from obesity; diabetes to Abdominal obesity-metabolic syndrome 3, OMIM:615812
Severe early-onset obesity v4.1 DYRK1B Achchuthan Shanmugasundram reviewed gene: DYRK1B: Rating: ; Mode of pathogenicity: None; Publications: 34193236, 34786696; Phenotypes: Abdominal obesity-metabolic syndrome 3, OMIM:615812; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.53 PLK1 Achchuthan Shanmugasundram Classified gene: PLK1 as Amber List (moderate evidence)
Intellectual disability v5.53 PLK1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Dmitrijs Rots (RadboudUMC), there is sufficient evidence for this gene to be promoted to GREEN at the next major review.
Intellectual disability v5.53 PLK1 Achchuthan Shanmugasundram Gene: plk1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.53 PLK1 Achchuthan Shanmugasundram Classified gene: PLK1 as Amber List (moderate evidence)
Intellectual disability v5.53 PLK1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Dmitrijs Rots (RadboudUMC), there is sufficient evidence for this gene to be promoted to GREEN at the next major review.
Intellectual disability v5.53 PLK1 Achchuthan Shanmugasundram Gene: plk1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.53 PLK1 Achchuthan Shanmugasundram Classified gene: PLK1 as Amber List (moderate evidence)
Intellectual disability v5.53 PLK1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Dmitrijs Rots (RadboudUMC), there is sufficient evidence for this gene to be promoted to GREEN at the next major review.
Intellectual disability v5.53 PLK1 Achchuthan Shanmugasundram Gene: plk1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.53 PLK1 Achchuthan Shanmugasundram Classified gene: PLK1 as Amber List (moderate evidence)
Intellectual disability v5.53 PLK1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Dmitrijs Rots (RadboudUMC), there is sufficient evidence for this gene to be promoted to GREEN at the next major review.
Intellectual disability v5.53 PLK1 Achchuthan Shanmugasundram Gene: plk1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.52 PLK1 Achchuthan Shanmugasundram Publications for gene: PLK1 were set to 33875846
Intellectual disability v5.52 PLK1 Achchuthan Shanmugasundram Publications for gene: PLK1 were set to 33875846
Intellectual disability v5.52 PLK1 Achchuthan Shanmugasundram Publications for gene: PLK1 were set to 33875846
Intellectual disability v5.51 PLK1 Achchuthan Shanmugasundram Publications for gene: PLK1 were set to 33875846
Intellectual disability v5.51 PLK1 Achchuthan Shanmugasundram Publications for gene: PLK1 were set to PMID: 33875846
Intellectual disability v5.50 PLK1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: PLK1.
Intellectual disability v5.50 PLK1 Achchuthan Shanmugasundram reviewed gene: PLK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33875846; Phenotypes: intellectual disability, MONDO:0001071; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v4.17 PLK1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: PLK1.
Early onset or syndromic epilepsy v4.17 PLK1 Achchuthan Shanmugasundram Classified gene: PLK1 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.17 PLK1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next major review.
Early onset or syndromic epilepsy v4.17 PLK1 Achchuthan Shanmugasundram Gene: plk1 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.16 PLK1 Achchuthan Shanmugasundram Publications for gene: PLK1 were set to 33875846
Early onset or syndromic epilepsy v4.15 PLK1 Achchuthan Shanmugasundram Publications for gene: PLK1 were set to
Early onset or syndromic epilepsy v4.14 PLK1 Achchuthan Shanmugasundram changed review comment from: As reviewed by Dmitrijs Rots (RadboudUMC), PMID:33875846 reported five unrelated cases identified with homozygous variants in PLK1 gene and presenting with a neurodevelopmental disorder phenotype characterised with seizures, microcephaly and global developmental delay.; to: As reviewed by Dmitrijs Rots (RadboudUMC), PMID:33875846 reported five unrelated cases identified with homozygous variants in PLK1 gene and presenting with a neurodevelopmental disorder phenotype characterised with seizures, microcephaly and global developmental delay.

This gene has not yet been associated with relevant phenotypes in OMIM or Gene2Phenotype.
Early onset or syndromic epilepsy v4.14 PLK1 Achchuthan Shanmugasundram reviewed gene: PLK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33875846; Phenotypes: developmental and epileptic encephalopathy, MONDO:0100062; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v4.14 OTUD7A Achchuthan Shanmugasundram changed review comment from: PMID:31997314 reported a patient presenting with severe global developmental delay, language impairment and epileptic encephalopathy and was identified with homozygous variant in OTUD7A gene (c.697C>T)/ p.Leu233Phe).

PMID:33381903 reported a patient with profound hypotonia, severe intellectual disability, and seizures and identified with biallelic loss-of-function variants in OTUD7A: a 15q13.3 deletion including the OTUD7A locus, and a frameshift OTUD7A variant c.1125del/ p.Glu375Aspfs*11.

PMID:36180924 reported a patient (patient #4) presenting with severe neurodevelopmental diseases and dysmorphic features and identified with hemizygous OTUD7A frameshift variant allele c.2023_2066del/ p.D675Hfs*188 in trans with the recurrent 15q13.3 BP4-BP5 deletion.

This gene has been reported in the DD panel of Gene2Phenotype (with 'limited' rating), but has not yet been associated with phenotypes in OMIM.

OTUD7A knockout mice exhibited reduced body weight, developmental delay, abnormal electroencephalography patterns and seizures, reduced ultrasonic vocalisations, decreased grip strength, impaired motor learning/motor coordination, and reduced acoustic startle (PMID:29395075). The function evidence also suggest that OTUD7A may be the critical “driver gene” in the 15q13.3 deletion syndrome.; to: PMID:31997314 reported a patient presenting with severe global developmental delay, language impairment and epileptic encephalopathy and was identified with homozygous variant in OTUD7A gene (c.697C>T)/ p.Leu233Phe).

PMID:33381903 reported a patient with profound hypotonia, severe intellectual disability, and seizures and identified with biallelic loss-of-function variants in OTUD7A: a 15q13.3 deletion including the OTUD7A locus, and a frameshift OTUD7A variant c.1125del/ p.Glu375Aspfs*11.

PMID:36180924 reported a patient (patient #4) presenting with severe neurodevelopmental diseases and dysmorphic features and identified with hemizygous OTUD7A frameshift variant allele c.2023_2066del/ p.D675Hfs*188 in trans with the recurrent 15q13.3 BP4-BP5 deletion.

OTUD7A knockout mice exhibited reduced body weight, developmental delay, abnormal electroencephalography patterns and seizures, reduced ultrasonic vocalisations, decreased grip strength, impaired motor learning/motor coordination, and reduced acoustic startle (PMID:29395075). The function evidence also suggest that OTUD7A may be the critical “driver gene” in the 15q13.3 deletion syndrome.

This gene has been reported in the DD panel of Gene2Phenotype (with 'limited' rating), but has not yet been associated with phenotypes in OMIM.
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram changed review comment from: PMID:31997314 reported a patient presenting with severe global developmental delay, language impairment and epileptic encephalopathy and was identified with homozygous variant in OTUD7A gene (c.697C>T)/ p.Leu233Phe).

PMID:33381903 reported a patient with profound hypotonia, severe intellectual disability, and seizures and identified with biallelic loss-of-function variants in OTUD7A: a 15q13.3 deletion including the OTUD7A locus, and a frameshift OTUD7A variant c.1125del/ p.Glu375Aspfs*11.

PMID:36180924 reported a patient (patient #4) presenting with severe neurodevelopmental diseases and dysmorphic features and identified with hemizygous OTUD7A frameshift variant allele c.2023_2066del/ p.D675Hfs*188 in trans with the recurrent 15q13.3 BP4-BP5 deletion.

OTUD7A knockout mice exhibited reduced body weight, developmental delay, abnormal electroencephalography patterns and seizures, reduced ultrasonic vocalisations, decreased grip strength, impaired motor learning/motor coordination, and reduced acoustic startle (PMID:29395075). The function evidence also suggest that OTUD7A may be the critical “driver gene” in the 15q13.3 deletion syndrome.; to: PMID:31997314 reported a patient presenting with severe global developmental delay, language impairment and epileptic encephalopathy and was identified with homozygous variant in OTUD7A gene (c.697C>T)/ p.Leu233Phe).

PMID:33381903 reported a patient with profound hypotonia, severe intellectual disability, and seizures and identified with biallelic loss-of-function variants in OTUD7A: a 15q13.3 deletion including the OTUD7A locus, and a frameshift OTUD7A variant c.1125del/ p.Glu375Aspfs*11.

PMID:36180924 reported a patient (patient #4) presenting with severe neurodevelopmental diseases and dysmorphic features and identified with hemizygous OTUD7A frameshift variant allele c.2023_2066del/ p.D675Hfs*188 in trans with the recurrent 15q13.3 BP4-BP5 deletion.

OTUD7A knockout mice exhibited reduced body weight, developmental delay, abnormal electroencephalography patterns and seizures, reduced ultrasonic vocalisations, decreased grip strength, impaired motor learning/motor coordination, and reduced acoustic startle (PMID:29395075). The function evidence also suggest that OTUD7A may be the critical “driver gene” in the 15q13.3 deletion syndrome.

This gene has been reported in the DD panel of Gene2Phenotype (with 'limited' rating), but has not yet been associated with phenotypes in OMIM.
Early onset or syndromic epilepsy v4.14 OTUD7A Achchuthan Shanmugasundram changed review comment from: PMID:31997314 reported a patient presenting with severe global developmental delay, language impairment and epileptic encephalopathy and was identified with homozygous variant in OTUD7A gene (c.697C>T)/ p.Leu233Phe).

PMID:33381903 reported a patient with profound hypotonia, severe intellectual disability, and seizures and identified with biallelic loss-of-function variants in OTUD7A: a 15q13.3 deletion including the OTUD7A locus, and a frameshift OTUD7A variant c.1125del/ p.Glu375Aspfs*11.

PMID:36180924 reported a patient (patient #4) presenting with severe neurodevelopmental diseases and dysmorphic features and identified with hemizygous OTUD7A frameshift variant allele c.2023_2066del/ p.D675Hfs*188 in trans with the recurrent 15q13.3 BP4-BP5 deletion.

OTUD7A knockout mice exhibited reduced body weight, developmental delay, abnormal electroencephalography patterns and seizures, reduced ultrasonic vocalisations, decreased grip strength, impaired motor learning/motor coordination, and reduced acoustic startle (PMID:29395075). The function evidence also suggest that OTUD7A may be the critical “driver gene” in the 15q13.3 deletion syndrome.; to: PMID:31997314 reported a patient presenting with severe global developmental delay, language impairment and epileptic encephalopathy and was identified with homozygous variant in OTUD7A gene (c.697C>T)/ p.Leu233Phe).

PMID:33381903 reported a patient with profound hypotonia, severe intellectual disability, and seizures and identified with biallelic loss-of-function variants in OTUD7A: a 15q13.3 deletion including the OTUD7A locus, and a frameshift OTUD7A variant c.1125del/ p.Glu375Aspfs*11.

PMID:36180924 reported a patient (patient #4) presenting with severe neurodevelopmental diseases and dysmorphic features and identified with hemizygous OTUD7A frameshift variant allele c.2023_2066del/ p.D675Hfs*188 in trans with the recurrent 15q13.3 BP4-BP5 deletion.

This gene has been reported in the DD panel of Gene2Phenotype (with 'limited' rating), but has not yet been associated with phenotypes in OMIM.

OTUD7A knockout mice exhibited reduced body weight, developmental delay, abnormal electroencephalography patterns and seizures, reduced ultrasonic vocalisations, decreased grip strength, impaired motor learning/motor coordination, and reduced acoustic startle (PMID:29395075). The function evidence also suggest that OTUD7A may be the critical “driver gene” in the 15q13.3 deletion syndrome.
Early onset or syndromic epilepsy v4.14 OTUD7A Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: OTUD7A.
Early onset or syndromic epilepsy v4.14 OTUD7A Achchuthan Shanmugasundram Classified gene: OTUD7A as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.14 OTUD7A Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (three unrelated cases with biallelic variants and supportive functional evidence from mouse models) for this gene to be promoted to green at the next major review.
Early onset or syndromic epilepsy v4.14 OTUD7A Achchuthan Shanmugasundram Gene: otud7a has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.13 OTUD7A Achchuthan Shanmugasundram Publications for gene: OTUD7A were set to 31997314; 29395075; 29395074; 33381903; 36180924
Early onset or syndromic epilepsy v4.13 OTUD7A Achchuthan Shanmugasundram Publications for gene: OTUD7A were set to 31997314; 29395075; 29395074
Early onset or syndromic epilepsy v4.12 OTUD7A Achchuthan Shanmugasundram reviewed gene: OTUD7A: Rating: GREEN; Mode of pathogenicity: None; Publications: 29395075, 31997314, 33381903, 36180924; Phenotypes: developmental and epileptic encephalopathy, MONDO:0100062; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Classified gene: OTUD7A as Amber List (moderate evidence)
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (three unrelated cases with biallelic variants and supportive functional evidence from mouse models) for this gene to be promoted to green at the next major review.
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Gene: otud7a has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.51 OTUD7A Achchuthan Shanmugasundram Classified gene: OTUD7A as Amber List (moderate evidence)
Intellectual disability v5.51 OTUD7A Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (three unrelated cases with biallelic variants and supportive functional evidence from mouse models) for this gene to be promoted to green at the next major review.
Intellectual disability v5.51 OTUD7A Achchuthan Shanmugasundram Gene: otud7a has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Classified gene: OTUD7A as Amber List (moderate evidence)
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (three unrelated cases with biallelic variants and supportive functional evidence from mouse models) for this gene to be promoted to green at the next major review.
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Gene: otud7a has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.51 OTUD7A Achchuthan Shanmugasundram Classified gene: OTUD7A as Amber List (moderate evidence)
Intellectual disability v5.51 OTUD7A Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (three unrelated cases with biallelic variants and supportive functional evidence from mouse models) for this gene to be promoted to green at the next major review.
Intellectual disability v5.51 OTUD7A Achchuthan Shanmugasundram Gene: otud7a has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.51 OTUD7A Achchuthan Shanmugasundram Classified gene: OTUD7A as Amber List (moderate evidence)
Intellectual disability v5.51 OTUD7A Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (three unrelated cases with biallelic variants and supportive functional evidence from mouse models) for this gene to be promoted to green at the next major review.
Intellectual disability v5.51 OTUD7A Achchuthan Shanmugasundram Gene: otud7a has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.51 OTUD7A Achchuthan Shanmugasundram Classified gene: OTUD7A as Amber List (moderate evidence)
Intellectual disability v5.51 OTUD7A Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (three unrelated cases with biallelic variants and supportive functional evidence from mouse models) for this gene to be promoted to green at the next major review.
Intellectual disability v5.51 OTUD7A Achchuthan Shanmugasundram Gene: otud7a has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Classified gene: OTUD7A as Amber List (moderate evidence)
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (three unrelated cases with biallelic variants and supportive functional evidence from mouse models) for this gene to be promoted to green at the next major review.
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Gene: otud7a has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Classified gene: OTUD7A as Amber List (moderate evidence)
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (three unrelated cases with biallelic variants and supportive functional evidence from mouse models) for this gene to be promoted to green at the next major review.
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Gene: otud7a has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: OTUD7A.
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Classified gene: OTUD7A as Amber List (moderate evidence)
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (three unrelated cases with biallelic variants and supportive functional evidence from mouse models) for this gene to be promoted to green at the next major review.
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Gene: otud7a has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Classified gene: OTUD7A as Amber List (moderate evidence)
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (three unrelated cases with biallelic variants and supportive functional evidence from mouse models) for this gene to be promoted to green at the next major review.
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Gene: otud7a has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.49 OTUD7A Achchuthan Shanmugasundram Publications for gene: OTUD7A were set to 31997314; 29395075; 29395074; 33381903; 36180924
Intellectual disability v5.49 OTUD7A Achchuthan Shanmugasundram Publications for gene: OTUD7A were set to 31997314; 29395075; 29395074; 33381903; 36180924
Intellectual disability v5.49 OTUD7A Achchuthan Shanmugasundram Publications for gene: OTUD7A were set to 31997314; 29395075; 29395074; 33381903; 36180924
Intellectual disability v5.49 OTUD7A Achchuthan Shanmugasundram Publications for gene: OTUD7A were set to 31997314; 29395075; 29395074; 33381903; 36180924
Intellectual disability v5.49 OTUD7A Achchuthan Shanmugasundram Publications for gene: OTUD7A were set to 31997314; 29395075; 29395074; 33381903; 36180924
Intellectual disability v5.49 OTUD7A Achchuthan Shanmugasundram Publications for gene: OTUD7A were set to 31997314; 29395075; 29395074; 33381903; 36180924
Intellectual disability v5.48 OTUD7A Achchuthan Shanmugasundram Publications for gene: OTUD7A were set to 31997314; 29395075; 29395074; 33381903; 36180924
Intellectual disability v5.48 OTUD7A Achchuthan Shanmugasundram Publications for gene: OTUD7A were set to 31997314; 29395075; 29395074
Intellectual disability v5.47 OTUD7A Achchuthan Shanmugasundram reviewed gene: OTUD7A: Rating: GREEN; Mode of pathogenicity: None; Publications: 29395075, 31997314, 33381903, 36180924; Phenotypes: intellectual disability, MONDO:0001071; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v3.13 GBF1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: GBF1.
Hereditary neuropathy or pain disorder v3.13 GBF1 Achchuthan Shanmugasundram Phenotypes for gene: GBF1 were changed from Axonal Neuropathy to Charcot-Marie-Tooth disease, axonal, type 2GG, OMIM:606483
Hereditary neuropathy or pain disorder v3.12 GBF1 Achchuthan Shanmugasundram Classified gene: GBF1 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v3.12 GBF1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark (Australian Genomics) and Dmitrijs Rots (RadboudUMC), this gene should be promoted to GREEN at the next major review as there are four unrelated families identified with monoallelic (2 de novo and 2 dominant) variants in GBF1 gene and reported with distal hereditary motor neuropathies (HMNs)/ axonal Charcot-Marie-Tooth neuropathy (CMT2).
Hereditary neuropathy or pain disorder v3.12 GBF1 Achchuthan Shanmugasundram Gene: gbf1 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v3.11 GBF1 Achchuthan Shanmugasundram commented on gene: GBF1: GBF1 is associated with relevant phenotype (MIM #606483) in OMIM, but not in Gene2Phenotype.
Hereditary neuropathy or pain disorder v3.11 GBF1 Achchuthan Shanmugasundram reviewed gene: GBF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32937143; Phenotypes: Charcot-Marie-Tooth disease, axonal, type 2GG, OMIM:606483; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v3.11 NUDT2 Achchuthan Shanmugasundram reviewed gene: NUDT2: Rating: AMBER; Mode of pathogenicity: None; Publications: 27431290, 30059600, 33058507; Phenotypes: Intellectual developmental disorder with or without peripheral neuropathy, OMIM:619844; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.11 CAPN3 Achchuthan Shanmugasundram changed review comment from: As reviewed by Dmitrijs Rots (RadboudUMC), there are at least 15 unrelated families identified with monoallelic variants (six missense variants and 2 small in-frame deletions) in CAPN3 gene reported with limb girdle muscle dystrophy (LGMD) in literature. These variants are associated with a milder LGMD phenotype than patients identified with recessive variants, and some carriers only present with isolated hyperCKaemia. In general, the autosomal dominant variants have been associated with milder and later-onset phenotypes (disease onset at young adulthood at the earliest).; to: As reviewed by Dmitrijs Rots (RadboudUMC), there are at least 15 unrelated families identified with monoallelic variants (six missense variants and 2 small in-frame deletions) in CAPN3 gene reported with limb girdle muscle dystrophy (LGMD) in literature. These variants are associated with a milder LGMD phenotype than patients identified with recessive variants, and some carriers only present with isolated hyperCKaemia. In general, the autosomal dominant variants have been associated with milder and later-onset phenotypes (disease onset at young adulthood at the earliest).

Both monoallelic and biallelic variants of this gene have been associated with relevant phenotypes in OMIM, but not in Gene2Phenotype.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.11 CAPN3 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There is sufficient evidence (~15 unrelated cases with monoallelic inheritance) for updating the MOI of this gene from 'BIALLELIC, autosomal or pseudoautosomal' to 'BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal' at the next major review.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.11 CAPN3 Achchuthan Shanmugasundram Mode of inheritance for gene: CAPN3 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.10 CAPN3 Achchuthan Shanmugasundram Tag Q2_23_MOI tag was added to gene: CAPN3.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.10 CAPN3 Achchuthan Shanmugasundram Phenotypes for gene: CAPN3 were changed from Muscular dystrophy, limb-girdle, autosomal recessive 1, OMIM:253600; Muscular dystrophy, limb-girdle, autosomal dominant 4, OMIM:618129 to Muscular dystrophy, limb-girdle, autosomal recessive 1, OMIM:253600; Muscular dystrophy, limb-girdle, autosomal dominant 4, OMIM:618129
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.9 CAPN3 Achchuthan Shanmugasundram Phenotypes for gene: CAPN3 were changed from Muscular dystrophy, limb-girdle, autosomal recessive 1, OMIM:253600; Muscular dystrophy, limb-girdle, autosomal dominant 4, OMIM:618129 to Muscular dystrophy, limb-girdle, autosomal recessive 1, OMIM:253600; Muscular dystrophy, limb-girdle, autosomal dominant 4, OMIM:618129
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.9 CAPN3 Achchuthan Shanmugasundram Phenotypes for gene: CAPN3 were changed from Muscular dystrophy, limb-girdle, autosomal recessive 1, OMIM:253600 to Muscular dystrophy, limb-girdle, autosomal recessive 1, OMIM:253600; Muscular dystrophy, limb-girdle, autosomal dominant 4, OMIM:618129
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.8 CAPN3 Achchuthan Shanmugasundram Publications for gene: CAPN3 were set to http://www.ncbi.nlm.nih.gov/books/NBK1408/; 32994280
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.7 CAPN3 Achchuthan Shanmugasundram changed review comment from: As reviewed by Dmitrijs Rots (RadboudUMC), there are at least 15 unrelated families identified with monoallelic variants (six missense variants and 2 small in-frame deletions) in CAPN3 gene reported with limb girdle muscle dystrophy (LGMD) in literature. These variants are associated with a milder LGMD phenotype than patients identified with recessive variants, and some carriers only present with isolated hyperCKaemia. In general, the autosomal dominant variants have been associated with milder and later-onset phenotypes (disease onset at young adulthood at the earliest).; to: As reviewed by Dmitrijs Rots (RadboudUMC), there are at least 15 unrelated families identified with monoallelic variants (six missense variants and 2 small in-frame deletions) in CAPN3 gene reported with limb girdle muscle dystrophy (LGMD) in literature. These variants are associated with a milder LGMD phenotype than patients identified with recessive variants, and some carriers only present with isolated hyperCKaemia. In general, the autosomal dominant variants have been associated with milder and later-onset phenotypes (disease onset at young adulthood at the earliest).
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.7 CAPN3 Achchuthan Shanmugasundram reviewed gene: CAPN3: Rating: GREEN; Mode of pathogenicity: None; Publications: 28881388, 32342993, 32557990, 32896923; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 1, OMIM:253600, Muscular dystrophy, limb-girdle, autosomal dominant 4, OMIM:618129; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.7 ACTN2 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: ACTN2.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.7 ACTN2 Achchuthan Shanmugasundram Classified gene: ACTN2 as Amber List (moderate evidence)
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.7 ACTN2 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.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.7 ACTN2 Achchuthan Shanmugasundram Gene: actn2 has been classified as Amber List (Moderate Evidence).
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.6 ACTN2 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There are at least 8 unrelated cases with monoallelic inheritance reported in literature.

Although there are three unrelated Japanese cases with biallelic inheritance reported in PMID:34471957, all of them were identified with the same homozygous variant.

Hence, 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' has currently been chosen as the MOI and it will be reviewed when more cases are reported with biallelic inheritance.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.6 ACTN2 Achchuthan Shanmugasundram Mode of inheritance for gene: ACTN2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.5 ACTN2 Achchuthan Shanmugasundram Phenotypes for gene: ACTN2 were changed from Myopathy, distal, 6, adult onset, OMIM:618655 to Myopathy, distal, 6, adult onset, OMIM:618655
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.5 ACTN2 Achchuthan Shanmugasundram Phenotypes for gene: ACTN2 were changed from Muscular dystrophy; hyperCKemia to Myopathy, distal, 6, adult onset, OMIM:618655
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.4 ACTN2 Achchuthan Shanmugasundram Publications for gene: ACTN2 were set to 30900782; 34170073; 34386585; 34471957; 36116040
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.4 ACTN2 Achchuthan Shanmugasundram Publications for gene: ACTN2 were set to 30900782; 34170073; 34386585; 34471957; 36116040
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.4 ACTN2 Achchuthan Shanmugasundram Publications for gene: ACTN2 were set to PMID: 34471957; 30701273; 30900782
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.3 ACTN2 Achchuthan Shanmugasundram reviewed gene: ACTN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30900782, 34170073, 34386585, 34471957, 36116040; Phenotypes: Myopathy, distal, 6, adult onset, OMIM:618655; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.47 CLCN4 Arina Puzriakova Phenotypes for gene: CLCN4 were changed from Mental retardation, X-linked 49-15 300114 to Raynaud-Claes syndrome, OMIM:300114
Early onset or syndromic epilepsy v4.12 CLCN4 Arina Puzriakova Phenotypes for gene: CLCN4 were changed from Raynaud-Claes syndrome 300114; Mental retardation, X-linked 49/15 to Raynaud-Claes syndrome, OMIM:300114
Limb disorders v4.2 MECOM Arina Puzriakova Phenotypes for gene: MECOM were changed from Radioulnar synostosis with amegakaryocytic thrombocytopenia 2, OMIM:616738; radioulnar synostosis with amegakaryocytic thrombocytopenia 2, MONDO:0014758 to Radioulnar synostosis with amegakaryocytic thrombocytopenia 2, OMIM:616738
Inherited bleeding disorders v1.175 MECOM Arina Puzriakova Phenotypes for gene: MECOM were changed from transcription factor and gives the same pathology (thrombocytopenia with bone defects) as HOXA11; Radioulnar synostosis with amegakaryocytic thrombocytopenia 2 to Radioulnar synostosis with amegakaryocytic thrombocytopenia 2, OMIM:616738
Bleeding and platelet disorders v3.2 MECOM Arina Puzriakova Phenotypes for gene: MECOM were changed from 616738 Radioulnar synostosis with amegakaryocytic thrombocytopenia 2 to Radioulnar synostosis with amegakaryocytic thrombocytopenia 2, OMIM:616738
Cytopenia - NOT Fanconi anaemia v3.2 MECOM Arina Puzriakova Phenotypes for gene: MECOM were changed from Radioulnar synostosis with amegakaryocytic thrombocytopenia 2, 616738; 616738 Radioulnar synostosis with amegakaryocytic thrombocytopenia 2 to Radioulnar synostosis with amegakaryocytic thrombocytopenia 2, OMIM:616738
Mitochondrial disorders v4.25 PDHX Arina Puzriakova Phenotypes for gene: PDHX were changed from Lacticacidemia due to PDX1 deficiency to Lacticacidemia due to PDX1 deficiency, OMIM:245349
Intellectual disability v5.46 PDHX Arina Puzriakova Phenotypes for gene: PDHX were changed from Lacticacidemia due to PDX1 deficiency 245349 to Lacticacidemia due to PDX1 deficiency, OMIM:245349
Early onset or syndromic epilepsy v4.11 PDHX Arina Puzriakova Phenotypes for gene: PDHX were changed from Lacticacidemia due to PDX1 deficiency 245349 to Lacticacidemia due to PDX1 deficiency, OMIM:245349
Likely inborn error of metabolism v4.25 PDHX Arina Puzriakova Phenotypes for gene: PDHX were changed from Lacticacidemia due to PDX1 deficiency; Pyruvate dehydrogenase E3 binding protein deficiency (Disorders of pyruvate metabolism) to Lacticacidemia due to PDX1 deficiency, OMIM:245349
Possible mitochondrial disorder - nuclear genes v3.26 PDHX Arina Puzriakova Phenotypes for gene: PDHX were changed from PYRUVATE DEHYDROGENASE E3-BINDING PROTEIN DEFICIENCY, 245349 to Lacticacidemia due to PDX1 deficiency, OMIM:245349
Undiagnosed metabolic disorders v1.583 PDHX Arina Puzriakova Phenotypes for gene: PDHX were changed from Pyruvate dehydrogenase E3 binding protein deficiency (Disorders of pyruvate metabolism); Lacticacidemia due to PDX1 deficiency to Lacticacidemia due to PDX1 deficiency, OMIM:245349
Pyruvate dehydrogenase (PDH) deficiency v1.34 PDHX Arina Puzriakova Phenotypes for gene: PDHX were changed from PYRUVATE DEHYDROGENASE E3-BINDING PROTEIN DEFICIENCY OMIM:245349; pyruvate dehydrogenase E3-binding protein deficiency MONDO:0009503 to Lacticacidemia due to PDX1 deficiency, OMIM:245349
Mitochondrial disorders v4.24 PDHB Arina Puzriakova Phenotypes for gene: PDHB were changed from Pyruvate dehydrogenase E1-beta deficiency, 614111 to Pyruvate dehydrogenase E1-beta deficiency, OMIM:614111
Intellectual disability v5.45 PDHB Arina Puzriakova Phenotypes for gene: PDHB were changed from Pyruvate dehydrogenase E1-beta deficiency, MIM#614111 to Pyruvate dehydrogenase E1-beta deficiency, OMIM:614111
Likely inborn error of metabolism v4.24 PDHB Arina Puzriakova Phenotypes for gene: PDHB were changed from Pyruvate dehydrogenase E1? subunit deficiency (Disorders of pyruvate metabolism); Pyruvate dehydrogenase E1-beta deficiency, 614111 to Pyruvate dehydrogenase E1-beta deficiency, OMIM:614111
Possible mitochondrial disorder - nuclear genes v3.25 PDHB Arina Puzriakova Phenotypes for gene: PDHB were changed from PYRUVATE DEHYDROGENASE E1-BETA DEFICIENCY, 614111 to Pyruvate dehydrogenase E1-beta deficiency, OMIM:614111
Undiagnosed metabolic disorders v1.582 PDHB Arina Puzriakova Phenotypes for gene: PDHB were changed from Pyruvate dehydrogenase E1? subunit deficiency (Disorders of pyruvate metabolism); Pyruvate dehydrogenase E1-beta deficiency, 614111 to Pyruvate dehydrogenase E1-beta deficiency, OMIM:614111
Pyruvate dehydrogenase (PDH) deficiency v1.33 PDHB Arina Puzriakova Phenotypes for gene: PDHB were changed from PYRUVATE DEHYDROGENASE E1-BETA DEFICIENCY OMIM:614111; pyruvate dehydrogenase E1-beta deficiency MONDO:0013580 to Pyruvate dehydrogenase E1-beta deficiency, OMIM:614111
Mitochondrial disorders v4.23 PC Arina Puzriakova Phenotypes for gene: PC were changed from Pyruvate carboxylase deficiency to Pyruvate carboxylase deficiency, OMIM:266150
Intellectual disability v5.44 PC Arina Puzriakova Phenotypes for gene: PC were changed from Pyruvate carboxylase deficiency, 266150; PYRUVATE CARBOXYLASE DEFICIENCY (PC DEFICIENCY) to Pyruvate carboxylase deficiency, OMIM:266150
Likely inborn error of metabolism v4.23 PC Arina Puzriakova Phenotypes for gene: PC were changed from Pyruvate carboxylase deficiency (Disorders of gluconeogenesis); lactic acidosis, hypotonia, encephalopathy; Pyruvate carboxylase deficiency 266150; Pyruvate carboxylase deficiency to Pyruvate carboxylase deficiency, OMIM:266150
Possible mitochondrial disorder - nuclear genes v3.24 PC Arina Puzriakova Phenotypes for gene: PC were changed from Pyruvate carboxylase deficiency, 266150 to Pyruvate carboxylase deficiency, OMIM:266150
Ketotic hypoglycaemia v1.8 PC Arina Puzriakova Phenotypes for gene: PC were changed from lactic acidosis, hypotonia, encephalopathy to Pyruvate carboxylase deficiency, OMIM:266150
Hyperammonaemia v1.14 PC Arina Puzriakova Phenotypes for gene: PC were changed from Pyruvate carboxylase deficiency 266150 to Pyruvate carboxylase deficiency, OMIM:266150
Undiagnosed metabolic disorders v1.581 PC Arina Puzriakova Phenotypes for gene: PC were changed from Pyruvate carboxylase deficiency (Disorders of gluconeogenesis); lactic acidosis, hypotonia, encephalopathy; Pyruvate carboxylase deficiency 266150; Pyruvate carboxylase deficiency to Pyruvate carboxylase deficiency, OMIM:266150
Childhood onset dystonia, chorea or related movement disorder v3.6 NDUFS1 Arina Puzriakova Phenotypes for gene: NDUFS1 were changed from Mitochondrial complex I deficiency, nuclear type 5, 618226 to Mitochondrial complex I deficiency, nuclear type 5, OMIM:618226
Mitochondrial disorders v4.22 NDUFS1 Arina Puzriakova Phenotypes for gene: NDUFS1 were changed from Isolated complex I deficiency; Mitochondrial complex I deficiency, 252010; Mitochondrial Diseases; Mitochondrial Respiratory Chain Complex I Deficiency to Mitochondrial complex I deficiency, nuclear type 5, OMIM:618226
Intellectual disability v5.43 NDUFS1 Arina Puzriakova Phenotypes for gene: NDUFS1 were changed from Mitochondrial complex I deficiency, 252010; LEIGH SYNDROME (NUCLEAR DNA MUTATION) to Mitochondrial complex I deficiency, nuclear type 5, OMIM:618226
Paediatric or syndromic cardiomyopathy v3.9 NDUFS1 Arina Puzriakova Phenotypes for gene: NDUFS1 were changed from Mitochondrial complex I deficiency, nuclear type 5, 618226 to Mitochondrial complex I deficiency, nuclear type 5, OMIM:618226
Early onset or syndromic epilepsy v4.10 NDUFS1 Arina Puzriakova Phenotypes for gene: NDUFS1 were changed from Mitochondrial complex I deficiency, 252010; LEIGH SYNDROME; MITOCHONDRIAL RESPIRATORY CHAIN COMPLEX I DEFICIENCY to Mitochondrial complex I deficiency, nuclear type 5, OMIM:618226
Likely inborn error of metabolism v4.22 NDUFS1 Arina Puzriakova Phenotypes for gene: NDUFS1 were changed from Mitochondrial complex I deficiency, 252010; Mitochondrial Diseases; Isolated complex I deficiency; Complex I (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits); Mitochondrial Respiratory Chain Complex I Deficiency to Mitochondrial complex I deficiency, nuclear type 5, OMIM:618226 Complex I (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits); Isolated complex I deficiency
Possible mitochondrial disorder - nuclear genes v3.23 NDUFS1 Arina Puzriakova Phenotypes for gene: NDUFS1 were changed from Mitochondrial complex I deficiency, nuclear type 5, 618226 to Mitochondrial complex I deficiency, nuclear type 5, OMIM:618226
Undiagnosed metabolic disorders v1.580 NDUFS1 Arina Puzriakova Phenotypes for gene: NDUFS1 were changed from Complex I (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits); Isolated complex I deficiency; Mitochondrial complex I deficiency, 252010; Mitochondrial Diseases; Mitochondrial Respiratory Chain Complex I Deficiency to Mitochondrial complex I deficiency, nuclear type 5, OMIM:618226 Complex I (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits); Isolated complex I deficiency
Mitochondrial disorder with complex I deficiency v3.5 NDUFS1 Arina Puzriakova Phenotypes for gene: NDUFS1 were changed from Mitochondrial complex I deficiency, nuclear type 5, 618226 to Mitochondrial complex I deficiency, nuclear type 5, OMIM:618226
Optic neuropathy v4.2 NDUFS1 Arina Puzriakova Phenotypes for gene: NDUFS1 were changed from MITOCHONDRIAL COMPLEX I DEFICIENCY, NUCLEAR TYPE 5, 618226 to Mitochondrial complex I deficiency, nuclear type 5, OMIM:618226
Inherited white matter disorders v1.175 NDUFS1 Arina Puzriakova Phenotypes for gene: NDUFS1 were changed from Mitochondrial complex I disorders; Mitochondrial complex I deficiency; Mitochondrial Leukoencephalopathy; General Leukodystrophy & Mitochondrial Leukoencephalopathy; MITOCHONDRIAL RESPIRATORY CHAIN COMPLEX I DEFICIENCY to Mitochondrial complex I deficiency, nuclear type 5, OMIM:618226
White matter disorders and cerebral calcification - narrow panel v3.7 NDUFS1 Arina Puzriakova Phenotypes for gene: NDUFS1 were changed from Mitochondrial complex I deficiency; Mitochondrial complex I disorders; General Leukodystrophy & Mitochondrial Leukoencephalopathy; Mitochondrial Leukoencephalopathy; MITOCHONDRIAL RESPIRATORY CHAIN COMPLEX I DEFICIENCY to Mitochondrial complex I deficiency, nuclear type 5, OMIM:618226
Intellectual disability v5.42 DARS2 Arina Puzriakova Phenotypes for gene: DARS2 were changed from Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, 611105; LEUKOENCEPHALOPATHY WITH BRAINSTEM AND SPINAL CORD INVOLVEMENT AND LACTATE ELEVATION to Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, OMIM:611105
White matter disorders and cerebral calcification - narrow panel v3.6 DARS2 Arina Puzriakova Phenotypes for gene: DARS2 were changed from General Leukodystrophy & Mitochondrial Leukoencephalopathy; Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation (LBSL); Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, 611105 to Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, OMIM:611105
Hereditary ataxia with onset in adulthood v4.9 DARS2 Arina Puzriakova Phenotypes for gene: DARS2 were changed from Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation; Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, 611105 to Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, OMIM:611105
Mitochondrial disorders v4.21 UQCC2 Arina Puzriakova Phenotypes for gene: UQCC2 were changed from Mitochondrial complex III deficiency, nuclear type 7, 615824 to Mitochondrial complex III deficiency, nuclear type 7, OMIM:615824
Likely inborn error of metabolism v4.21 UQCC2 Arina Puzriakova Phenotypes for gene: UQCC2 were changed from Isolated complex III deficiency to Mitochondrial complex III deficiency, nuclear type 7, OMIM:615824
Paediatric or syndromic cardiomyopathy v3.8 UQCC2 Arina Puzriakova Phenotypes for gene: UQCC2 were changed from Mitochondrial complex III deficiency, nuclear type 7, 615824 to Mitochondrial complex III deficiency, nuclear type 7, OMIM:615824
Clefting v4.2 UQCC2 Arina Puzriakova Phenotypes for gene: UQCC2 were changed from MITOCHONDRIAL COMPLEX III DEFICIENCY, NUCLEAR TYPE 7; MC3DN7 to Mitochondrial complex III deficiency, nuclear type 7, OMIM:615824
Possible mitochondrial disorder - nuclear genes v3.22 UQCC2 Arina Puzriakova Phenotypes for gene: UQCC2 were changed from Mitochondrial complex III deficiency, nuclear type 7, 615824 to Mitochondrial complex III deficiency, nuclear type 7, OMIM:615824
Mitochondrial disorder with complex III deficiency v2.2 UQCC2 Arina Puzriakova Phenotypes for gene: UQCC2 were changed from Mitochondrial complex III deficiency, nuclear type 7, 615824 to Mitochondrial complex III deficiency, nuclear type 7, OMIM:615824
Mitochondrial disorders v4.20 SUCLA2 Arina Puzriakova Phenotypes for gene: SUCLA2 were changed from Disorders of mitochondrial DNA maintenance and integrity; Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonicaciduria), 612073; Mitochondrial DNA Depletion Syndrome to Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), OMIM:612073; Required for mtDNA maintenance (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Disorders of mitochondrial DNA maintenance and integrity
Childhood onset dystonia, chorea or related movement disorder v3.5 SUCLA2 Arina Puzriakova Phenotypes for gene: SUCLA2 were changed from Dystonia; Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), 612073 to Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), OMIM:612073
Intellectual disability v5.41 SUCLA2 Arina Puzriakova Phenotypes for gene: SUCLA2 were changed from Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria); OMIM #612073 to Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), OMIM:612073
Hereditary neuropathy or pain disorder v3.11 SUCLA2 Arina Puzriakova Phenotypes for gene: SUCLA2 were changed from Leigh like syndrome, deafness, progressive dystonia, mild methylmaolic acidaemia; Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), 612073 to Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), OMIM:612073
Early onset or syndromic epilepsy v4.9 SUCLA2 Arina Puzriakova Phenotypes for gene: SUCLA2 were changed from Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), 612073 to Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), OMIM:612073
Likely inborn error of metabolism v4.20 SUCLA2 Arina Puzriakova Phenotypes for gene: SUCLA2 were changed from Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonicaciduria), 612073; Mitochondrial DNA Depletion Syndrome; Disorders of mitochondrial DNA maintenance and integrity; Required for mtDNA maintenance (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) to Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), OMIM:612073; Required for mtDNA maintenance (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Disorders of mitochondrial DNA maintenance and integrity
Hereditary neuropathy v1.466 SUCLA2 Arina Puzriakova Phenotypes for gene: SUCLA2 were changed from Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), 612073; Leigh like syndrome, deafness, progressive dystonia, mild methylmaolic acidaemia to Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), OMIM:612073
Possible mitochondrial disorder - nuclear genes v3.21 SUCLA2 Arina Puzriakova Phenotypes for gene: SUCLA2 were changed from Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), 612073 to Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), OMIM:612073
Undiagnosed metabolic disorders v1.579 SUCLA2 Arina Puzriakova Phenotypes for gene: SUCLA2 were changed from Required for mtDNA maintenance (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Disorders of mitochondrial DNA maintenance and integrity; Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonicaciduria), 612073; Mitochondrial DNA Depletion Syndrome to Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), OMIM:612073; Required for mtDNA maintenance (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Disorders of mitochondrial DNA maintenance and integrity
Mitochondrial DNA maintenance disorder v3.4 SUCLA2 Arina Puzriakova Phenotypes for gene: SUCLA2 were changed from Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), 612073 to Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), OMIM:612073
Inherited white matter disorders v1.174 SUCLA2 Arina Puzriakova Phenotypes for gene: SUCLA2 were changed from Mitochondrial Leukoencephalopathy; Mitochondrial DNA depletion syndrome 5; Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria) to Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), OMIM:612073
Structural basal ganglia disorders v1.36 SUCLA2 Arina Puzriakova Phenotypes for gene: SUCLA2 were changed from to Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), OMIM:612073
White matter disorders and cerebral calcification - narrow panel v3.5 SUCLA2 Arina Puzriakova Phenotypes for gene: SUCLA2 were changed from Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria); Mitochondrial Leukoencephalopathy; Mitochondrial DNA depletion syndrome 5 to Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), OMIM:612073
Rhabdomyolysis and metabolic muscle disorders v3.2 SUCLA2 Arina Puzriakova Phenotypes for gene: SUCLA2 were changed from Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria) 612073 to Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), OMIM:612073
Mitochondrial disorders v4.19 NDUFV2 Arina Puzriakova Phenotypes for gene: NDUFV2 were changed from Isolated complex I deficiency; Mitochondrial complex I deficiency, 252010; Mitochondrial Respiratory Chain Complex I Deficiency to Mitochondrial complex I deficiency, nuclear type 7, OMIM:618229
Likely inborn error of metabolism v4.19 NDUFV2 Arina Puzriakova Phenotypes for gene: NDUFV2 were changed from Mitochondrial complex I deficiency, 252010; Isolated complex I deficiency; Complex I (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits); Mitochondrial Respiratory Chain Complex I Deficiency to Mitochondrial complex I deficiency, nuclear type 7, OMIM:618229; Complex I (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits)
Undiagnosed metabolic disorders v1.578 NDUFV2 Arina Puzriakova Phenotypes for gene: NDUFV2 were changed from Complex I (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits); Isolated complex I deficiency; Mitochondrial complex I deficiency, 252010; Mitochondrial Respiratory Chain Complex I Deficiency to Mitochondrial complex I deficiency, nuclear type 7, OMIM:618229; Complex I (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits)
Mitochondrial disorders v4.18 NDUFB7 Arina Puzriakova Phenotypes for gene: NDUFB7 were changed from Congenital lactic acidosis; hypertrophic cardiomyopathy to ?Mitochondrial complex I deficiency, nuclear type 39, OMIM:620135
Likely inborn error of metabolism v4.18 NDUFB7 Arina Puzriakova Phenotypes for gene: NDUFB7 were changed from Congenital lactic acidosis; hypertrophic cardiomyopathy to ?Mitochondrial complex I deficiency, nuclear type 39, OMIM:620135
Possible mitochondrial disorder - nuclear genes v3.20 NDUFB7 Arina Puzriakova Mode of inheritance for gene: NDUFB7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Possible mitochondrial disorder - nuclear genes v3.19 NDUFB7 Arina Puzriakova Phenotypes for gene: NDUFB7 were changed from No OMIM phenotype to ?Mitochondrial complex I deficiency, nuclear type 39, OMIM:620135
Mitochondrial disorder with complex I deficiency v3.4 NDUFB7 Arina Puzriakova Phenotypes for gene: NDUFB7 were changed from Congenital lactic acidosis; hypertrophic cardiomyopathy to ?Mitochondrial complex I deficiency, nuclear type 39, OMIM:620135
Mitochondrial disorders v4.17 NDUFB3 Arina Puzriakova Phenotypes for gene: NDUFB3 were changed from Isolated complex I deficiency; Mitochondrial complex I deficiency, 252010 to Mitochondrial complex I deficiency, nuclear type 25, OMIM:618246
Likely inborn error of metabolism v4.17 NDUFB3 Arina Puzriakova Phenotypes for gene: NDUFB3 were changed from Complex I (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits); Mitochondrial complex I deficiency, 252010; Isolated complex I deficiency to Mitochondrial complex I deficiency, nuclear type 25, OMIM:618246
Paediatric or syndromic cardiomyopathy v3.7 NDUFB3 Arina Puzriakova Phenotypes for gene: NDUFB3 were changed from Mitochondrial complex I deficiency, nuclear type 25, 618246 to Mitochondrial complex I deficiency, nuclear type 25, OMIM:618246
Possible mitochondrial disorder - nuclear genes v3.18 NDUFB3 Arina Puzriakova Phenotypes for gene: NDUFB3 were changed from Mitochondrial complex I deficiency, nuclear type 25, 618246 to Mitochondrial complex I deficiency, nuclear type 25, OMIM:618246
Undiagnosed metabolic disorders v1.577 NDUFB3 Arina Puzriakova Phenotypes for gene: NDUFB3 were changed from Complex I (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits); Isolated complex I deficiency; Mitochondrial complex I deficiency, 252010 to Mitochondrial complex I deficiency, nuclear type 25, OMIM:618246
Mitochondrial disorder with complex I deficiency v3.3 NDUFB3 Arina Puzriakova Phenotypes for gene: NDUFB3 were changed from Mitochondrial complex I deficiency, nuclear type 25, 618246 to Mitochondrial complex I deficiency, nuclear type 25, OMIM:618246
Mitochondrial disorders v4.16 NDUFA6 Arina Puzriakova Phenotypes for gene: NDUFA6 were changed from Mitochondrial complex I deficiency, nuclear type 33, 618253 to Mitochondrial complex I deficiency, nuclear type 33, OMIM:618253
Likely inborn error of metabolism v4.16 NDUFA6 Arina Puzriakova Phenotypes for gene: NDUFA6 were changed from Mitochondrial complex I deficiency, nuclear type 33, 618253; No OMIM phenotype; Isolated complex I deficiency to Mitochondrial complex I deficiency, nuclear type 33, OMIM:618253
Paediatric or syndromic cardiomyopathy v3.6 NDUFA6 Arina Puzriakova Phenotypes for gene: NDUFA6 were changed from Mitochondrial complex I deficiency, nuclear type 33, 618253 to Mitochondrial complex I deficiency, nuclear type 33, OMIM:618253
Possible mitochondrial disorder - nuclear genes v3.17 NDUFA6 Arina Puzriakova Phenotypes for gene: NDUFA6 were changed from Mitochondrial complex I deficiency, nuclear type 33, 618253 to Mitochondrial complex I deficiency, nuclear type 33, OMIM:618253
Mitochondrial disorder with complex I deficiency v3.2 NDUFA6 Arina Puzriakova Phenotypes for gene: NDUFA6 were changed from Mitochondrial complex I deficiency, nuclear type 33, 618253 to Mitochondrial complex I deficiency, nuclear type 33, OMIM:618253
Likely inborn error of metabolism v4.15 NADK2 Arina Puzriakova Phenotypes for gene: NADK2 were changed from ?2,4-dienoyl-CoA reductase deficiency 616034 to 2,4-dienoyl-CoA reductase deficiency, OMIM:616034
Intellectual disability v5.40 NADK2 Arina Puzriakova Phenotypes for gene: NADK2 were changed from ?2,4-dienoyl-CoA reductase deficiency to 2,4-dienoyl-CoA reductase deficiency, OMIM:616034
Possible mitochondrial disorder - nuclear genes v3.16 NADK2 Arina Puzriakova Phenotypes for gene: NADK2 were changed from ?2,4-dienoyl-CoA reductase deficiency, 616034 to 2,4-dienoyl-CoA reductase deficiency, OMIM:616034
Mitochondrial disorders v4.15 NADK2 Arina Puzriakova Phenotypes for gene: NADK2 were changed from ?2,4-dienoyl-CoA reductase deficiency 616034 to 2,4-dienoyl-CoA reductase deficiency, OMIM:616034
White matter disorders and cerebral calcification - narrow panel v3.4 MTFMT Arina Puzriakova Phenotypes for gene: MTFMT were changed from Combined oxidative phosphorylation deficiency 15; 22499348; 614947; 23499752 to Combined oxidative phosphorylation deficiency 15, OMIM:614947
Mitochondrial disorders v4.14 MRPS14 Arina Puzriakova Phenotypes for gene: MRPS14 were changed from No OMIM phenotype to ?Combined oxidative phosphorylation deficiency 38, OMIM:618378
Likely inborn error of metabolism v4.14 MRPS14 Arina Puzriakova Phenotypes for gene: MRPS14 were changed from ?Combined oxidative phosphorylation deficiency 38, 618378 to ?Combined oxidative phosphorylation deficiency 38, OMIM:618378
Possible mitochondrial disorder - nuclear genes v3.15 MRPS14 Arina Puzriakova Phenotypes for gene: MRPS14 were changed from No OMIM phenotype to ?Combined oxidative phosphorylation deficiency 38, OMIM:618378
Likely inborn error of metabolism v4.13 MPC1 Arina Puzriakova Phenotypes for gene: MPC1 were changed from Mitochondrial pyruvate carrier deficiency, 614741 to Mitochondrial pyruvate carrier deficiency, OMIM:614741
Mitochondrial disorders v4.13 MPC1 Arina Puzriakova Phenotypes for gene: MPC1 were changed from Mitochondrial pyruvate carrier deficiency, 614741 to Mitochondrial pyruvate carrier deficiency, OMIM:614741
Possible mitochondrial disorder - nuclear genes v3.14 MPC1 Arina Puzriakova Phenotypes for gene: MPC1 were changed from Lactic acidosis and hyperpyruvatemia to Mitochondrial pyruvate carrier deficiency, OMIM:614741
Possible mitochondrial disorder - nuclear genes v3.13 GFM2 Arina Puzriakova Publications for gene: GFM2 were set to 29075935
Mitochondrial disorders v4.12 GFM2 Arina Puzriakova Phenotypes for gene: GFM2 were changed from Early-onset neurological presentations of mitochondrial disease; Multiple respiratory chain complex deficiencies (disorders of protein synthesis) to Combined oxidative phosphorylation deficiency 39, OMIM:618397; Early-onset neurological presentations of mitochondrial disease and impaired expression of OXPHOS subunits
Arthrogryposis v5.4 GFM2 Arina Puzriakova Phenotypes for gene: GFM2 were changed from Combined oxidative phosphorylation deficiency 39, 618397; arthrogryposis multiplex congenita to Combined oxidative phosphorylation deficiency 39, OMIM:618397
Likely inborn error of metabolism v4.12 GFM2 Arina Puzriakova Phenotypes for gene: GFM2 were changed from Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Early-onset neurological presentations of mitochondrial disease to Combined oxidative phosphorylation deficiency 39, OMIM:618397
Possible mitochondrial disorder - nuclear genes v3.12 GFM2 Arina Puzriakova Phenotypes for gene: GFM2 were changed from Early-onset neurological presentations of mitochondrial disease and impaired expression of OXPHOS subunits to Combined oxidative phosphorylation deficiency 39, OMIM:618397; Early-onset neurological presentations of mitochondrial disease and impaired expression of OXPHOS subunits
Likely inborn error of metabolism v4.11 GATB Arina Puzriakova Mode of inheritance for gene: GATB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v4.11 GATB Arina Puzriakova Mode of inheritance for gene: GATB was changed from to BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v4.10 GATB Arina Puzriakova Phenotypes for gene: GATB were changed from Multiple respiratory chain complex deficiencies (disorders of protein synthesis) to ?Combined oxidative phosphorylation deficiency 41, OMIM:618838
Possible mitochondrial disorder - nuclear genes v3.11 GATB Arina Puzriakova Phenotypes for gene: GATB were changed from Mitochondrial cardiomyopathy disorder to ?Combined oxidative phosphorylation deficiency 41, OMIM:618838
Mitochondrial disorders v4.10 GATB Arina Puzriakova Phenotypes for gene: GATB were changed from Multiple respiratory chain complex deficiencies (disorders of protein synthesis) to ?Combined oxidative phosphorylation deficiency 41, OMIM:618838
Likely inborn error of metabolism v4.9 ECHS1 Arina Puzriakova Phenotypes for gene: ECHS1 were changed from Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency to Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency, OMIM:616277
Pyruvate dehydrogenase (PDH) deficiency v1.32 ECHS1 Arina Puzriakova Phenotypes for gene: ECHS1 were changed from MITOCHONDRIAL SHORT-CHAIN ENOYL-CoA HYDRATASE 1 DEFICIENCY OMIM:616277; mitochondrial short-chain Enoyl-Coa hydratase 1 deficiency MONDO:0014563 to Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency, OMIM:616277
Undiagnosed metabolic disorders v1.576 ECHS1 Arina Puzriakova Phenotypes for gene: ECHS1 were changed from Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency to Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency, OMIM:616277
Mitochondrial disorders v4.9 ECHS1 Arina Puzriakova Phenotypes for gene: ECHS1 were changed from Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency to Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency, OMIM:616277
Possible mitochondrial disorder - nuclear genes v3.10 ECHS1 Arina Puzriakova Phenotypes for gene: ECHS1 were changed from MITOCHONDRIAL SHORT-CHAIN ENOYL-CoA HYDRATASE 1 DEFICIENCY, 616277 to Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency, OMIM:616277
Childhood onset dystonia, chorea or related movement disorder v3.4 ECHS1 Arina Puzriakova Phenotypes for gene: ECHS1 were changed from Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency, 616277 to Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency, OMIM:616277
Intellectual disability v5.39 COX14 Arina Puzriakova Mode of inheritance for gene: COX14 was changed from MITOCHONDRIAL to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v4.8 COA6 Arina Puzriakova Phenotypes for gene: COA6 were changed from Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 4 616501 to Mitochondrial complex IV deficiency, nuclear type 13, OMIM:616501
Likely inborn error of metabolism v4.8 COA6 Arina Puzriakova Phenotypes for gene: COA6 were changed from ?{Fatal infantile cardiomyopathy, association with}, 604377 to Mitochondrial complex IV deficiency, nuclear type 13, OMIM:616501
Paediatric or syndromic cardiomyopathy v3.5 COA6 Arina Puzriakova Phenotypes for gene: COA6 were changed from Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 4 616501 to Mitochondrial complex IV deficiency, nuclear type 13, OMIM:616501
Possible mitochondrial disorder - nuclear genes v3.9 COA6 Arina Puzriakova Phenotypes for gene: COA6 were changed from Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 4 616501 to Mitochondrial complex IV deficiency, nuclear type 13, OMIM:616501
Mitochondrial disorder with complex IV deficiency v3.2 COA6 Arina Puzriakova Phenotypes for gene: COA6 were changed from Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 4 616501 to Mitochondrial complex IV deficiency, nuclear type 13, OMIM:616501
Possible mitochondrial disorder - nuclear genes v3.8 C19orf70 Arina Puzriakova Phenotypes for gene: C19orf70 were changed from No OMIM phenotype to Combined oxidative phosphorylation deficiency 37, OMIM:618329
Likely inborn error of metabolism v4.7 ATP5O Arina Puzriakova Phenotypes for gene: ATP5O were changed from No OMIM phenotype to Mitochondrial complex V (ATP synthase) deficiency
Mitochondrial disorders v4.7 ATP5O Arina Puzriakova Phenotypes for gene: ATP5O were changed from No OMIM phenotype to Mitochondrial complex V (ATP synthase) deficiency
Likely inborn error of metabolism v4.6 ATP5O Arina Puzriakova Publications for gene: ATP5O were set to 34954817; 35621276
Mitochondrial disorders v4.6 ATP5O Arina Puzriakova Publications for gene: ATP5O were set to
Likely inborn error of metabolism v4.6 ATP5O Arina Puzriakova Publications for gene: ATP5O were set to
Possible mitochondrial disorder - nuclear genes v3.7 ATP5O Arina Puzriakova Phenotypes for gene: ATP5O were changed from No OMIM phenotype to Mitochondrial complex V (ATP synthase) deficiency
Mitochondrial disorders v4.5 ATP5O Arina Puzriakova Mode of inheritance for gene: ATP5O was changed from to BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v4.5 ATP5O Arina Puzriakova Mode of inheritance for gene: ATP5O was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Possible mitochondrial disorder - nuclear genes v3.6 ATP5O Arina Puzriakova Mode of inheritance for gene: ATP5O was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Possible mitochondrial disorder - nuclear genes v3.5 ATP5O Arina Puzriakova Publications for gene: ATP5O were set to
Mitochondrial disorders v4.4 ATP5O Arina Puzriakova Classified gene: ATP5O as Amber List (moderate evidence)
Mitochondrial disorders v4.4 ATP5O Arina Puzriakova Added comment: Comment on list classification: There are now sufficient unrelated cases reported (3) to promote this gene to Green at the next GMS panel update.
Mitochondrial disorders v4.4 ATP5O Arina Puzriakova Gene: atp5o has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v4.3 ATP5O Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: ATP5O.
Likely inborn error of metabolism v4.4 ATP5O Arina Puzriakova Classified gene: ATP5O as Amber List (moderate evidence)
Likely inborn error of metabolism v4.4 ATP5O Arina Puzriakova Added comment: Comment on list classification: There are now sufficient unrelated cases reported (3) to promote this gene to Green at the next GMS panel update.
Likely inborn error of metabolism v4.4 ATP5O Arina Puzriakova Gene: atp5o has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v4.3 ATP5O Arina Puzriakova reviewed gene: ATP5O: Rating: GREEN; Mode of pathogenicity: None; Publications: 34954817, 35621276; Phenotypes: Mitochondrial complex V (ATP synthase) deficiency; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Possible mitochondrial disorder - nuclear genes v3.4 ATP5O Arina Puzriakova Classified gene: ATP5O as Amber List (moderate evidence)
Possible mitochondrial disorder - nuclear genes v3.4 ATP5O Arina Puzriakova Added comment: Comment on list classification: There are now sufficient unrelated cases reported (3) to promote this gene to Green at the next GMS panel update.
Possible mitochondrial disorder - nuclear genes v3.4 ATP5O Arina Puzriakova Gene: atp5o has been classified as Amber List (Moderate Evidence).
Possible mitochondrial disorder - nuclear genes v3.3 ATP5O Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: ATP5O.
Possible mitochondrial disorder - nuclear genes v3.3 ATP5O Arina Puzriakova reviewed gene: ATP5O: Rating: GREEN; Mode of pathogenicity: None; Publications: 34954817, 35621276; Phenotypes: Mitochondrial complex V (ATP synthase) deficiency; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v4.3 ATP5O Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: ATP5O.
Likely inborn error of metabolism v4.3 ATP5O Arina Puzriakova reviewed gene: ATP5O: Rating: GREEN; Mode of pathogenicity: None; Publications: 34954817, 35621276; Phenotypes: Mitochondrial complex V (ATP synthase) deficiency; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Distal myopathies v3.5 ADSSL1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: ADSSL1.
Distal myopathies v3.5 ADSSL1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There are sufficient evidence (~70 unrelated cases) for the association of biallelic variants from this gene with distal myopathies. The onset of distal muscle weakness is during adolescence/ adulthood.

This gene has also been associated with distal myopathy in OMIM (MIM #617030).

This gene can therefore be promoted to GREEN at the next major review.; to: Comment on list classification: There is sufficient evidence (~70 unrelated cases) for the association of biallelic variants from this gene with distal myopathies. The onset of distal muscle weakness is during adolescence/ adulthood.

This gene has also been associated with distal myopathy in OMIM (MIM #617030).

This gene can therefore be promoted to GREEN at the next major review.
Early onset or syndromic epilepsy v4.8 ATP5O Arina Puzriakova Entity copied from Mitochondrial disorder with complex V deficiency v2.5
Early onset or syndromic epilepsy v4.8 ATP5O Arina Puzriakova gene: ATP5O was added
gene: ATP5O was added to Early onset or syndromic epilepsy. Sources: NHS GMS,Expert Review Amber
new-gene-name, Q2_23_promote_green tags were added to gene: ATP5O.
Mode of inheritance for gene: ATP5O was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP5O were set to 34954817; 35621276
Phenotypes for gene: ATP5O were set to Mitochondrial complex V (ATP synthase) deficiency
Mitochondrial disorder with complex V deficiency v2.5 ATP5O Arina Puzriakova Phenotypes for gene: ATP5O were changed from No OMIM phenotype to Mitochondrial complex V (ATP synthase) deficiency
Mitochondrial disorder with complex V deficiency v2.4 ATP5O Arina Puzriakova Publications for gene: ATP5O were set to
Distal myopathies v3.5 ADSSL1 Achchuthan Shanmugasundram Publications for gene: ADSSL1 were set to 26506222; 28268051; 32331917; 32646962; 35668205
Mitochondrial disorder with complex V deficiency v2.3 ATP5O Arina Puzriakova Mode of inheritance for gene: ATP5O was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Distal myopathies v3.6 ADSSL1 Achchuthan Shanmugasundram Publications for gene: ADSSL1 were set to 26506222; 28268051; 32331917; 32646962; 35668205
Distal myopathies v3.6 ADSSL1 Achchuthan Shanmugasundram Publications for gene: ADSSL1 were set to 26506222; 28268051; 32331917; 32646962; 35668205
Mitochondrial disorder with complex V deficiency v2.2 ATP5O Arina Puzriakova Classified gene: ATP5O as Amber List (moderate evidence)
Mitochondrial disorder with complex V deficiency v2.2 ATP5O Arina Puzriakova Added comment: Comment on list classification: There are now sufficient unrelated cases reported (3) to promote this gene to Green at the next GMS panel update.
Mitochondrial disorder with complex V deficiency v2.2 ATP5O Arina Puzriakova Gene: atp5o has been classified as Amber List (Moderate Evidence).
Distal myopathies v3.6 ADSSL1 Achchuthan Shanmugasundram Publications for gene: ADSSL1 were set to 26506222; 28268051; 32331917; 32646962; 35668205
Distal myopathies v3.4 ADSSL1 Achchuthan Shanmugasundram Deleted their comment
Distal myopathies v3.4 ADSSL1 Achchuthan Shanmugasundram Phenotypes for gene: ADSSL1 were changed from Myopathy, distal, 5, OMIM:617030 to Myopathy, distal, 5, OMIM:617030
Distal myopathies v3.5 ADSSL1 Achchuthan Shanmugasundram Publications for gene: ADSSL1 were set to 26506222; 28268051; 32331917; 32646962; 35668205
Distal myopathies v3.5 ADSSL1 Achchuthan Shanmugasundram Publications for gene: ADSSL1 were set to 26506222; 28268051; 32331917; 32646962; 35668205
Distal myopathies v3.5 ADSSL1 Achchuthan Shanmugasundram Publications for gene: ADSSL1 were set to 26506222
Distal myopathies v3.4 ADSSL1 Achchuthan Shanmugasundram Phenotypes for gene: ADSSL1 were changed from Myopathy, distal, 5, OMIM:617030 to Myopathy, distal, 5, OMIM:617030
Distal myopathies v3.4 ADSSL1 Achchuthan Shanmugasundram Phenotypes for gene: ADSSL1 were changed from Myopathy, distal, 5, OMIM:617030 to Myopathy, distal, 5, OMIM:617030
Distal myopathies v3.4 ADSSL1 Achchuthan Shanmugasundram Phenotypes for gene: ADSSL1 were changed from Myopathy, distal, 5, OMIM:617030 to Myopathy, distal, 5, OMIM:617030
Distal myopathies v3.3 ADSSL1 Achchuthan Shanmugasundram Phenotypes for gene: ADSSL1 were changed from Myopathy, distal, 5, OMIM:617030 to Myopathy, distal, 5, OMIM:617030
Mitochondrial disorder with complex V deficiency v2.1 ATP5O Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: ATP5O.
Distal myopathies v3.3 ADSSL1 Achchuthan Shanmugasundram Phenotypes for gene: ADSSL1 were changed from Myopathy, distal, 5, OMIM:617030 to Myopathy, distal, 5, OMIM:617030
Distal myopathies v3.3 ADSSL1 Achchuthan Shanmugasundram Phenotypes for gene: ADSSL1 were changed from Myopathy, distal, 5, 617030 to Myopathy, distal, 5, OMIM:617030
Mitochondrial disorder with complex V deficiency v2.1 ATP5O Arina Puzriakova reviewed gene: ATP5O: Rating: GREEN; Mode of pathogenicity: None; Publications: 34954817, 35621276; Phenotypes: Mitochondrial complex V (ATP synthase) deficiency; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Distal myopathies v3.2 ADSSL1 Achchuthan Shanmugasundram Classified gene: ADSSL1 as Amber List (moderate evidence)
Distal myopathies v3.2 ADSSL1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are sufficient evidence (~70 unrelated cases) for the association of biallelic variants from this gene with distal myopathies. The onset of distal muscle weakness is during adolescence/ adulthood.

This gene has also been associated with distal myopathy in OMIM (MIM #617030).

This gene can therefore be promoted to GREEN at the next major review.
Distal myopathies v3.2 ADSSL1 Achchuthan Shanmugasundram Gene: adssl1 has been classified as Amber List (Moderate Evidence).
Distal myopathies v3.2 ADSSL1 Achchuthan Shanmugasundram Classified gene: ADSSL1 as Amber List (moderate evidence)
Distal myopathies v3.2 ADSSL1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are sufficient evidence (~70 unrelated cases) for the association of biallelic variants from this gene with distal myopathies. The onset of distal muscle weakness is during adolescence/ adulthood.

This gene has also been associated with distal myopathy in OMIM (MIM #617030).

This gene can therefore be promoted to GREEN at the next major review.
Distal myopathies v3.2 ADSSL1 Achchuthan Shanmugasundram Gene: adssl1 has been classified as Amber List (Moderate Evidence).
Distal myopathies v3.1 ADSSL1 Achchuthan Shanmugasundram reviewed gene: ADSSL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26506222, 28268051, 32331917, 32646962, 35668205; Phenotypes: Myopathy, distal, 5, OMIM:617030; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital myopathy v4.26 ADSSL1 Achchuthan Shanmugasundram changed review comment from: As reviewed by Zornitza Stark (Australian Genomics), evidence from scientific literature show that the onset of distal myopathy caused by ADSSL1 variants is during late childhood/ adolescence in majority of reported cases.

Patients with ADSSL1 myopathy typically visit the hospital for muscle weakness during adulthood; however, all the patients have a history of being the slowest runner among their peers during childhood, which is a characteristic feature of ADSSL1 myopathy. Patients with ADSSL1 myopathy develop distal muscle weakness, including significant post-puberty grip weakness, which occurs in all patients (PMID:35668205).

However, the review of previously reported patients in PMID:28268051 described patients with early childhood onset, with the youngest patient reported at 5 years of age.

PMID:31680123 reported one case identified with homozygous frameshift variant and presented with congenital joint contractures and a more severe neurological phenotype,; to: As reviewed by Zornitza Stark (Australian Genomics), evidence from scientific literature show that the onset of distal myopathy caused by ADSSL1 variants is during late childhood/ adolescence in the reported cases.

Patients with ADSSL1 myopathy typically visit the hospital for muscle weakness during adulthood; however, all the patients have a history of being the slowest runner among their peers during childhood, which is a characteristic feature of ADSSL1 myopathy. Patients with ADSSL1 myopathy develop distal muscle weakness, including significant post-puberty grip weakness, which occurs in all patients (PMID:35668205).

Patients reported in PMIDs: 26506222 & 28268051 developed diffuse muscle weakness initially around 5-8 years of age, although distal leg weakness started at adolescence (13-17 years of age).

PMID:31680123 reported one case identified with homozygous frameshift variant and presented with congenital joint contractures and a more severe neurological phenotype.

As the diffuse muscle weakness started at childhood in at least nine cases and there is a case with congenital joint contractures, and this gene was added green as per expert review, we should keep this gene green on this panel.
Congenital myopathy v4.26 CCDC78 Achchuthan Shanmugasundram Tag Q4_22_MOI was removed from gene: CCDC78.
Congenital myopathy v4.26 CCDC78 Achchuthan Shanmugasundram edited their review of gene: CCDC78: Changed phenotypes to: centronuclear myopathy-4, OMIM:614807
Congenital myopathy v4.26 ADSSL1 Achchuthan Shanmugasundram changed review comment from: As reviewed by Zornitza Stark (Australian Genomics), evidence from scientific literature show that the onset of distal myopathy caused by ADSSL1 variants is during late childhood/ adolescence in majority of reported cases.

Patients with ADSSL1 myopathy typically visit the hospital for muscle weakness during adulthood; however, all the patients have a history of being the slowest runner among their peers during childhood, which is a characteristic feature of ADSSL1 myopathy. Patients with ADSSL1 myopathy develop distal muscle weakness, including significant post-puberty grip weakness, which occurs in all patients.

However, the review of previously reported patients in PMID:28268051 described patients with early childhood onset, with the youngest patient reported at 5 years of age.

PMID:31680123 reported one case identified with homozygous frameshift variant and presented with congenital joint contractures and a more severe neurological phenotype,; to: As reviewed by Zornitza Stark (Australian Genomics), evidence from scientific literature show that the onset of distal myopathy caused by ADSSL1 variants is during late childhood/ adolescence in majority of reported cases.

Patients with ADSSL1 myopathy typically visit the hospital for muscle weakness during adulthood; however, all the patients have a history of being the slowest runner among their peers during childhood, which is a characteristic feature of ADSSL1 myopathy. Patients with ADSSL1 myopathy develop distal muscle weakness, including significant post-puberty grip weakness, which occurs in all patients (PMID:35668205).

However, the review of previously reported patients in PMID:28268051 described patients with early childhood onset, with the youngest patient reported at 5 years of age.

PMID:31680123 reported one case identified with homozygous frameshift variant and presented with congenital joint contractures and a more severe neurological phenotype,
Congenital myopathy v4.26 ADSSL1 Achchuthan Shanmugasundram reviewed gene: ADSSL1: Rating: AMBER; Mode of pathogenicity: None; Publications: 26506222, 28268051, 31680123, 32331917, 32646962, 35668205; Phenotypes: Myopathy, distal, 5, OMIM:617030; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.38 NAPB Arina Puzriakova Phenotypes for gene: NAPB were changed from Early infantile epileptic encephalopathy to Developmental and epileptic encephalopathy 107, OMIM:620033
Early onset or syndromic epilepsy v4.7 NAPB Arina Puzriakova Phenotypes for gene: NAPB were changed from Early infantile epileptic encephalopathy to Developmental and epileptic encephalopathy 107, OMIM:620033
Severe microcephaly v4.8 NAPB Arina Puzriakova Phenotypes for gene: NAPB were changed from Early infantile epileptic encephalopathy to Developmental and epileptic encephalopathy 107, OMIM:620033
Intellectual disability v5.37 IQSEC2 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There is sufficient evidence (>3 female cases with monoallelic variants causing ID) to suggest that MOI should be updated to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' in the next major review.

In addition, intellectual disability (MIM #309530) has been associated in both OMIM and Gene2Phenotype with X-linked dominant inheritance.
Intellectual disability v5.37 IQSEC2 Achchuthan Shanmugasundram Mode of inheritance for gene: IQSEC2 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 v5.37 IQSEC2 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There is sufficient evidence (>3 female cases with monoallelic variants causing ID) to suggest that MOI should be updated to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' in the next major review.

In addition, intellectual disability (MIM #309530) has been associated in both OMIM and Gene2Phenotype with X-linked dominant inheritance.
Intellectual disability v5.37 IQSEC2 Achchuthan Shanmugasundram Mode of inheritance for gene: IQSEC2 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 v5.37 IQSEC2 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There is sufficient evidence (>3 female cases with monoallelic variants causing ID) to suggest that MOI should be updated to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' in the next major review.

In addition, intellectual disability (MIM #309530) has been associated in both OMIM and Gene2Phenotype with X-linked dominant inheritance.
Intellectual disability v5.37 IQSEC2 Achchuthan Shanmugasundram Mode of inheritance for gene: IQSEC2 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 v5.37 IQSEC2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.37 IQSEC2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.37 IQSEC2 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There is sufficient evidence (>3 female cases with monoallelic variants causing ID) to suggest that MOI should be updated to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' in the next major review.

In addition, intellectual disability (MIM #309530) has been associated in both OMIM and Gene2Phenotype with X-linked dominant inheritance.
Intellectual disability v5.37 IQSEC2 Achchuthan Shanmugasundram Mode of inheritance for gene: IQSEC2 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 v5.36 IQSEC2 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There is sufficient evidence (>3 female cases with monoallelic variants causing ID) to suggest that MOI should be updated to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' in the next major review.

In addition, intellectual disability (MIM #309530) has been associated in both OMIM and Gene2Phenotype with X-linked dominant inheritance.
Intellectual disability v5.36 IQSEC2 Achchuthan Shanmugasundram Mode of inheritance for gene: IQSEC2 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 v5.36 IQSEC2 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There is sufficient evidence (>3 female cases with monoallelic variants causing ID) to suggest that MOI should be updated to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' in the next major review.

In addition, intellectual disability (MIM #309530) has been associated in both OMIM and Gene2Phenotype with X-linked dominant inheritance.
Intellectual disability v5.36 IQSEC2 Achchuthan Shanmugasundram Mode of inheritance for gene: IQSEC2 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 v5.35 IQSEC2 Achchuthan Shanmugasundram changed review comment from: There are more than 20 unrelated cases identified with variants in IQSEC2 gene, as reported in publications. Moderate to severe intellectual disability was present in all affected males.

De novo, truncating variants correlate with severe disease in both female and male patients harboring an IQSEC2 alteration. Missense variants in male and female patients account for a milder disease overall, with more severe symptoms in males than females. This evidence suggests that the MOI should be 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)'.

Both OMIM and Gene2Phenotype have associated X-linked dominant variants in IQSEC2 with intellectual disability (MIM #309530); to: There are more than 20 unrelated cases identified with variants in IQSEC2 gene, as reported in publications. Moderate to severe intellectual disability was present in all affected males.

De novo, truncating variants correlate with severe disease in both female and male patients harboring an IQSEC2 alteration. Missense variants in male and female patients account for a milder disease overall, with more severe symptoms in males than females.
Intellectual disability v5.35 IQSEC2 Achchuthan Shanmugasundram Publications for gene: IQSEC2 were set to 20473311; 23674175; 30842726; 31415821; 33368194
Intellectual disability v5.36 IQSEC2 Achchuthan Shanmugasundram Publications for gene: IQSEC2 were set to 20473311; 23674175; 30842726; 31415821; 33368194
Intellectual disability v5.36 IQSEC2 Achchuthan Shanmugasundram Publications for gene: IQSEC2 were set to 20473311; 23674175; 30842726; 31415821; 33368194
Intellectual disability v5.36 IQSEC2 Achchuthan Shanmugasundram Publications for gene: IQSEC2 were set to 20473311; 23674175; 30842726; 31415821; 33368194
Intellectual disability v5.35 IQSEC2 Achchuthan Shanmugasundram Publications for gene: IQSEC2 were set to 20473311; 23674175; 30842726; 31415821; 33368194
Intellectual disability v5.36 IQSEC2 Achchuthan Shanmugasundram Publications for gene: IQSEC2 were set to 20473311; 23674175; 30842726; 31415821; 33368194
Intellectual disability v5.35 IQSEC2 Achchuthan Shanmugasundram Publications for gene: IQSEC2 were set to 20473311; 23674175; 30842726; 31415821; 33368194
Intellectual disability v5.35 IQSEC2 Achchuthan Shanmugasundram Publications for gene: IQSEC2 were set to 20473311; 23674175; 30842726; 31415821; 33368194
Intellectual disability v5.35 IQSEC2 Achchuthan Shanmugasundram Publications for gene: IQSEC2 were set to
Intellectual disability v5.34 IQSEC2 Achchuthan Shanmugasundram Tag Q2_23_MOI tag was added to gene: IQSEC2.
Intellectual disability v5.34 IQSEC2 Achchuthan Shanmugasundram reviewed gene: IQSEC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20473311, 23674175, 30842726, 31415821, 33368194; Phenotypes: Intellectual developmental disorder, X-linked 1, OMIM:309530; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Inherited breast cancer and ovarian cancer v2.6 Eleanor Williams Panel version 2.5 has been signed off on 2023-04-12
Inherited breast cancer and ovarian cancer v2.5 RAD51D Eleanor Williams commented on gene: RAD51D
Inherited breast cancer and ovarian cancer v2.5 RAD51D Eleanor Williams Classified gene: RAD51D as Green List (high evidence)
Inherited breast cancer and ovarian cancer v2.5 RAD51D Eleanor Williams Gene: rad51d has been classified as Green List (High Evidence).
Inherited breast cancer and ovarian cancer v2.4 RAD51D Eleanor Williams gene: RAD51D was added
gene: RAD51D was added to Inherited breast cancer and ovarian cancer. Sources: Expert list
Mode of inheritance for gene: RAD51D was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: RAD51D were set to {Breast-ovarian cancer, familial, susceptibility to, 4}, OMIM:614291
Inherited breast cancer and ovarian cancer v2.3 RAD51C Eleanor Williams commented on gene: RAD51C
Inherited breast cancer and ovarian cancer v2.3 RAD51C Eleanor Williams Classified gene: RAD51C as Green List (high evidence)
Inherited breast cancer and ovarian cancer v2.3 RAD51C Eleanor Williams Gene: rad51c has been classified as Green List (High Evidence).
Inherited breast cancer and ovarian cancer v2.2 RAD51C Eleanor Williams gene: RAD51C was added
gene: RAD51C was added to Inherited breast cancer and ovarian cancer. Sources: Expert list
Mode of inheritance for gene: RAD51C was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: RAD51C were set to {Breast-ovarian cancer, familial, susceptibility to, 3}, OMIM:613399
Unexplained young onset end-stage renal disease v3.1 RET Achchuthan Shanmugasundram Tag Q2_23_MOI tag was added to gene: RET.
Unexplained young onset end-stage renal disease v3.1 RET Achchuthan Shanmugasundram reviewed gene: RET: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.34 HUWE1 Achchuthan Shanmugasundram Tag Q2_23_MOI tag was added to gene: HUWE1.
Intellectual disability v5.34 HUWE1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.34 HUWE1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.34 HUWE1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.34 HUWE1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.34 HUWE1 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There is sufficient evidence for updating the MOI of this gene 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)'.
Intellectual disability v5.34 HUWE1 Achchuthan Shanmugasundram Mode of inheritance for gene: HUWE1 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 v5.34 HUWE1 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There is sufficient evidence for updating the MOI of this gene 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)'.
Intellectual disability v5.34 HUWE1 Achchuthan Shanmugasundram Mode of inheritance for gene: HUWE1 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 v5.34 HUWE1 Achchuthan Shanmugasundram changed review comment from: Comment on mode of inheritance: There is sufficient evidence for updating the MOI of this gene 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)'.; to: Comment on mode of inheritance: There is sufficient evidence for updating the MOI of this gene 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)' in the next major review.
Intellectual disability v5.34 HUWE1 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There is sufficient evidence for updating the MOI of this gene 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)'.
Intellectual disability v5.34 HUWE1 Achchuthan Shanmugasundram Mode of inheritance for gene: HUWE1 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 v5.33 HUWE1 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There is sufficient evidence for updating the MOI of this gene 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)'.
Intellectual disability v5.33 HUWE1 Achchuthan Shanmugasundram Mode of inheritance for gene: HUWE1 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 v5.33 HUWE1 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There is sufficient evidence for updating the MOI of this gene 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)'.
Intellectual disability v5.33 HUWE1 Achchuthan Shanmugasundram Mode of inheritance for gene: HUWE1 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 v5.32 HUWE1 Achchuthan Shanmugasundram Publications for gene: HUWE1 were set to 7943042; 18252223; 24896178; 25529582; 29180823
Intellectual disability v5.34 HUWE1 Achchuthan Shanmugasundram Publications for gene: HUWE1 were set to 7943042; 18252223; 24896178; 25529582; 29180823
Intellectual disability v5.32 HUWE1 Achchuthan Shanmugasundram Publications for gene: HUWE1 were set to 7943042; 18252223; 24896178; 25529582; 29180823
Intellectual disability v5.33 HUWE1 Achchuthan Shanmugasundram Publications for gene: HUWE1 were set to 7943042; 18252223; 24896178; 25529582; 29180823
Intellectual disability v5.31 HUWE1 Achchuthan Shanmugasundram Phenotypes for gene: HUWE1 were changed from Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590 to Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590
Intellectual disability v5.33 HUWE1 Achchuthan Shanmugasundram Publications for gene: HUWE1 were set to 7943042; 18252223; 24896178; 25529582; 29180823
Intellectual disability v5.33 HUWE1 Achchuthan Shanmugasundram Publications for gene: HUWE1 were set to 7943042; 18252223; 24896178; 25529582; 29180823
Intellectual disability v5.32 HUWE1 Achchuthan Shanmugasundram Phenotypes for gene: HUWE1 were changed from Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590 to Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590
Intellectual disability v5.32 HUWE1 Achchuthan Shanmugasundram Phenotypes for gene: HUWE1 were changed from Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590 to Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590
Intellectual disability v5.32 HUWE1 Achchuthan Shanmugasundram Publications for gene: HUWE1 were set to
Intellectual disability v5.32 HUWE1 Achchuthan Shanmugasundram Phenotypes for gene: HUWE1 were changed from Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590 to Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590
Intellectual disability v5.32 HUWE1 Achchuthan Shanmugasundram Phenotypes for gene: HUWE1 were changed from Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590 to Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590
Intellectual disability v5.32 HUWE1 Achchuthan Shanmugasundram Phenotypes for gene: HUWE1 were changed from Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590 to Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590
Intellectual disability v5.32 HUWE1 Achchuthan Shanmugasundram Phenotypes for gene: HUWE1 were changed from Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590 to Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590
Intellectual disability v5.31 HUWE1 Achchuthan Shanmugasundram Phenotypes for gene: HUWE1 were changed from Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590 to Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590
Intellectual disability v5.31 HUWE1 Achchuthan Shanmugasundram Phenotypes for gene: HUWE1 were changed from Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590 to Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590
Intellectual disability v5.31 HUWE1 Achchuthan Shanmugasundram Phenotypes for gene: HUWE1 were changed from Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590 to Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590
Intellectual disability v5.31 HUWE1 Achchuthan Shanmugasundram Phenotypes for gene: HUWE1 were changed from Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590 to Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590
Intellectual disability v5.31 HUWE1 Achchuthan Shanmugasundram Phenotypes for gene: HUWE1 were changed from Mental retardation, X-linked syndromic, Turner type, 300706; MENTAL RETARDATION SYNDROMIC X-LINKED TURNER TYPE (MRXST) to Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590
Intellectual disability v5.30 HUWE1 Achchuthan Shanmugasundram reviewed gene: HUWE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29180823; Phenotypes: Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590; 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 v5.30 TRAPPC10 Achchuthan Shanmugasundram Classified gene: TRAPPC10 as Amber List (moderate evidence)
Intellectual disability v5.30 TRAPPC10 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as there are only two unrelated cases with intellectual disability and global developmental delay. Although there are functional studies available, no cognitive defects were reported in the mouse model.

The 'watchlist' tag has been added to review this gene rating regularly in light of any new evidence.
Intellectual disability v5.30 TRAPPC10 Achchuthan Shanmugasundram Gene: trappc10 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.30 TRAPPC10 Achchuthan Shanmugasundram Classified gene: TRAPPC10 as Amber List (moderate evidence)
Intellectual disability v5.30 TRAPPC10 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as there are only two unrelated cases with intellectual disability and global developmental delay. Although there are functional studies available, no cognitive defects were reported in the mouse model.

The 'watchlist' tag has been added to review this gene rating regularly in light of any new evidence.
Intellectual disability v5.30 TRAPPC10 Achchuthan Shanmugasundram Gene: trappc10 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.30 TRAPPC10 Achchuthan Shanmugasundram Classified gene: TRAPPC10 as Amber List (moderate evidence)
Intellectual disability v5.30 TRAPPC10 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as there are only two unrelated cases with intellectual disability and global developmental delay. Although there are functional studies available, no cognitive defects were reported in the mouse model.

The 'watchlist' tag has been added to review this gene rating regularly in light of any new evidence.
Intellectual disability v5.30 TRAPPC10 Achchuthan Shanmugasundram Gene: trappc10 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.30 TRAPPC10 Achchuthan Shanmugasundram Classified gene: TRAPPC10 as Amber List (moderate evidence)
Intellectual disability v5.30 TRAPPC10 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as there are only two unrelated cases with intellectual disability and global developmental delay. Although there are functional studies available, no cognitive defects were reported in the mouse model.

The 'watchlist' tag has been added to review this gene rating regularly in light of any new evidence.
Intellectual disability v5.30 TRAPPC10 Achchuthan Shanmugasundram Gene: trappc10 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.30 TRAPPC10 Achchuthan Shanmugasundram Classified gene: TRAPPC10 as Amber List (moderate evidence)
Intellectual disability v5.30 TRAPPC10 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as there are only two unrelated cases with intellectual disability and global developmental delay. Although there are functional studies available, no cognitive defects were reported in the mouse model.

The 'watchlist' tag has been added to review this gene rating regularly in light of any new evidence.
Intellectual disability v5.30 TRAPPC10 Achchuthan Shanmugasundram Gene: trappc10 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.29 TRAPPC10 Achchuthan Shanmugasundram Classified gene: TRAPPC10 as Amber List (moderate evidence)
Intellectual disability v5.29 TRAPPC10 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as there are only two unrelated cases with intellectual disability and global developmental delay. Although there are functional studies available, no cognitive defects were reported in the mouse model.

The 'watchlist' tag has been added to review this gene rating regularly in light of any new evidence.
Intellectual disability v5.29 TRAPPC10 Achchuthan Shanmugasundram Gene: trappc10 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.29 TRAPPC10 Achchuthan Shanmugasundram Classified gene: TRAPPC10 as Amber List (moderate evidence)
Intellectual disability v5.29 TRAPPC10 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as there are only two unrelated cases with intellectual disability and global developmental delay. Although there are functional studies available, no cognitive defects were reported in the mouse model.

The 'watchlist' tag has been added to review this gene rating regularly in light of any new evidence.
Intellectual disability v5.29 TRAPPC10 Achchuthan Shanmugasundram Gene: trappc10 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.28 TRAPPC10 Achchuthan Shanmugasundram Phenotypes for gene: TRAPPC10 were changed from Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027 to Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027
Intellectual disability v5.28 TRAPPC10 Achchuthan Shanmugasundram Phenotypes for gene: TRAPPC10 were changed from Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027 to Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027
Intellectual disability v5.27 TRAPPC10 Achchuthan Shanmugasundram Phenotypes for gene: TRAPPC10 were changed from Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027 to Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027
Intellectual disability v5.28 TRAPPC10 Achchuthan Shanmugasundram Phenotypes for gene: TRAPPC10 were changed from Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027 to Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027
Intellectual disability v5.28 TRAPPC10 Achchuthan Shanmugasundram Phenotypes for gene: TRAPPC10 were changed from Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027 to Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027
Intellectual disability v5.29 TRAPPC10 Achchuthan Shanmugasundram Phenotypes for gene: TRAPPC10 were changed from Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027 to Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027
Intellectual disability v5.30 TRAPPC10 Achchuthan Shanmugasundram Phenotypes for gene: TRAPPC10 were changed from Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027 to Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027
Intellectual disability v5.27 TRAPPC10 Achchuthan Shanmugasundram Phenotypes for gene: TRAPPC10 were changed from Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027 to Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027
Intellectual disability v5.28 TRAPPC10 Achchuthan Shanmugasundram Phenotypes for gene: TRAPPC10 were changed from Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027 to Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027
Intellectual disability v5.28 TRAPPC10 Achchuthan Shanmugasundram Tag watchlist tag was added to gene: TRAPPC10.
Intellectual disability v5.28 TRAPPC10 Achchuthan Shanmugasundram Phenotypes for gene: TRAPPC10 were changed from Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027 to Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027
Intellectual disability v5.28 TRAPPC10 Achchuthan Shanmugasundram Phenotypes for gene: TRAPPC10 were changed from Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027 to Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027
Intellectual disability v5.29 TRAPPC10 Achchuthan Shanmugasundram Phenotypes for gene: TRAPPC10 were changed from Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027 to Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027
Intellectual disability v5.27 TRAPPC10 Achchuthan Shanmugasundram Publications for gene: TRAPPC10 were set to 30167849; 35298461
Intellectual disability v5.28 TRAPPC10 Achchuthan Shanmugasundram Phenotypes for gene: TRAPPC10 were changed from Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027 to Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027
Intellectual disability v5.28 TRAPPC10 Achchuthan Shanmugasundram Phenotypes for gene: TRAPPC10 were changed from Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027 to Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027
Intellectual disability v5.28 TRAPPC10 Achchuthan Shanmugasundram Phenotypes for gene: TRAPPC10 were changed from Intellectual disability, MONDO:0001071 to Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027
Intellectual disability v5.27 TRAPPC10 Achchuthan Shanmugasundram Publications for gene: TRAPPC10 were set to 30167849; 35298461
Intellectual disability v5.27 TRAPPC10 Achchuthan Shanmugasundram Publications for gene: TRAPPC10 were set to 30167849; 35298461
Intellectual disability v5.27 TRAPPC10 Achchuthan Shanmugasundram Publications for gene: TRAPPC10 were set to 30167849; 35298461
Intellectual disability v5.26 TRAPPC10 Achchuthan Shanmugasundram Publications for gene: TRAPPC10 were set to 30167849; 35298461
Intellectual disability v5.26 TRAPPC10 Achchuthan Shanmugasundram Publications for gene: TRAPPC10 were set to 30167849; 35298461
Intellectual disability v5.27 TRAPPC10 Achchuthan Shanmugasundram Publications for gene: TRAPPC10 were set to 30167849; 35298461
Intellectual disability v5.27 TRAPPC10 Achchuthan Shanmugasundram Publications for gene: TRAPPC10 were set to 30167849; 35298461
Intellectual disability v5.27 TRAPPC10 Achchuthan Shanmugasundram Publications for gene: TRAPPC10 were set to 30167849; 35298461
Intellectual disability v5.27 TRAPPC10 Achchuthan Shanmugasundram Publications for gene: TRAPPC10 were set to 30167849; 35298461
Intellectual disability v5.26 TRAPPC10 Achchuthan Shanmugasundram Publications for gene: TRAPPC10 were set to 30167849; 35298461
Intellectual disability v5.26 TRAPPC10 Achchuthan Shanmugasundram Publications for gene: TRAPPC10 were set to 30167849; 35298461
Intellectual disability v5.26 TRAPPC10 Achchuthan Shanmugasundram Publications for gene: TRAPPC10 were set to 30167849
Intellectual disability v5.25 TRAPPC10 Achchuthan Shanmugasundram reviewed gene: TRAPPC10: Rating: AMBER; Mode of pathogenicity: None; Publications: 30167849, 35298461; Phenotypes: Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Adult onset neurodegenerative disorder v4.13 SPG7 Sarah Leigh changed review comment from: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be both monoallelic and biallelic, autosomal or pseudoautosomal.; to: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal.
Severe microcephaly v4.7 TRAPPC10 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: TRAPPC10.
Severe microcephaly v4.7 TRAPPC10 Achchuthan Shanmugasundram Classified gene: TRAPPC10 as Amber List (moderate evidence)
Severe microcephaly v4.7 TRAPPC10 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for associating this gene with severe microcephaly (two unrelated cases and supporting functional evidence) and hence can be promoted to GREEN at the next major review.
Severe microcephaly v4.7 TRAPPC10 Achchuthan Shanmugasundram Gene: trappc10 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v4.6 TRAPPC10 Achchuthan Shanmugasundram changed review comment from: Biallelic variants in TRAPPC10 have been identified in two unrelated consanguineous Pakistani families that have been reported with severe microcephalic neurodevelopmental disorder. In addition, neuroanatomical brain defects and microcephaly, paralleling findings seen in the human patients were seen in Trappc9-/- mouse model.

This gene has been associated with relevant phenotypes in both OMIM (MIM #620027) and Gene2Phenotype (with 'limited' rating).; to: Biallelic variants in TRAPPC10 have been identified in two unrelated consanguineous Pakistani families that have been reported with severe microcephalic neurodevelopmental disorder. In addition, neuroanatomical brain defects and microcephaly (paralleling findings seen in the human patients) were seen in Trappc9-/- mouse model.

This gene has been associated with relevant phenotypes in both OMIM (MIM #620027) and Gene2Phenotype (with 'limited' rating).
Severe microcephaly v4.6 TRAPPC10 Achchuthan Shanmugasundram Phenotypes for gene: TRAPPC10 were changed from microcephaly (disease), MONDO:0001149; Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027 to Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027
Severe microcephaly v4.5 TRAPPC10 Achchuthan Shanmugasundram Phenotypes for gene: TRAPPC10 were changed from microcephaly (disease), MONDO:0001149 to microcephaly (disease), MONDO:0001149; Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027
Severe microcephaly v4.4 TRAPPC10 Achchuthan Shanmugasundram Publications for gene: TRAPPC10 were set to 30167849
Severe microcephaly v4.3 TRAPPC10 Achchuthan Shanmugasundram reviewed gene: TRAPPC10: Rating: GREEN; Mode of pathogenicity: None; Publications: 30167849, 35298461; Phenotypes: Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Adult onset neurodegenerative disorder v4.13 GBE1 Sarah Leigh reviewed gene: GBE1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Adult onset neurodegenerative disorder v4.13 GBE1 Sarah Leigh Tag Q2_23_promote_green tag was added to gene: GBE1.
Adult onset neurodegenerative disorder v4.13 GBE1 Sarah Leigh Phenotypes for gene: GBE1 were changed from Polyglucosan body disease, adult form, OMIM:263570 to Polyglucosan body disease, adult form, OMIM:263570; adult polyglucosan body disease, MONDO:0009897
Adult onset neurodegenerative disorder v4.12 GBE1 Sarah Leigh Publications for gene: GBE1 were set to 20301758; 26194201
Intellectual disability v5.25 KDM5A Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Tracy Lester (Genetics laboratory, Oxford UK), there is sufficient evidence for this gene to be promoted to GREEN in the next major review.

This gene can be associated with both monoallelic and biallelic inheritance as there are at least three cases each for both of them.; to: Comment on list classification:, There is sufficient evidence for this gene to be promoted to GREEN at the next major review.

This gene can be associated with both monoallelic and biallelic inheritance as there are at least three cases each for both of them.
Intellectual disability v5.25 KDM5A Achchuthan Shanmugasundram Tag Q2_23_NHS_review tag was added to gene: KDM5A.
Intellectual disability v5.25 KDM5A Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: KDM5A.
Intellectual disability v5.25 KDM5A Achchuthan Shanmugasundram Phenotypes for gene: KDM5A were changed from AUTOSOMAL RECESSIVE MENTAL RETARDATION; autism spectrum disorder, MONDO:0005258; intellectual disability, MONDO:0001071 to AUTOSOMAL RECESSIVE MENTAL RETARDATION; autism spectrum disorder, MONDO:0005258; intellectual disability, MONDO:0001071
Intellectual disability v5.25 KDM5A Achchuthan Shanmugasundram Phenotypes for gene: KDM5A were changed from AUTOSOMAL RECESSIVE MENTAL RETARDATION; autism spectrum disorder, MONDO:0005258; intellectual disability, MONDO:0001071 to AUTOSOMAL RECESSIVE MENTAL RETARDATION; autism spectrum disorder, MONDO:0005258; intellectual disability, MONDO:0001071
Intellectual disability v5.25 KDM5A Achchuthan Shanmugasundram Phenotypes for gene: KDM5A were changed from AUTOSOMAL RECESSIVE MENTAL RETARDATION; autism spectrum disorder, MONDO:0005258; intellectual disability, MONDO:0001071 to AUTOSOMAL RECESSIVE MENTAL RETARDATION; autism spectrum disorder, MONDO:0005258; intellectual disability, MONDO:0001071
Intellectual disability v5.25 KDM5A Achchuthan Shanmugasundram Phenotypes for gene: KDM5A were changed from AUTOSOMAL RECESSIVE MENTAL RETARDATION to AUTOSOMAL RECESSIVE MENTAL RETARDATION; autism spectrum disorder, MONDO:0005258; intellectual disability, MONDO:0001071
Intellectual disability v5.24 KDM5A Achchuthan Shanmugasundram changed review comment from: PMID:21937992 reported a family with recessive missense KDM5A variant presenting with an undefined developmental disorder characterised with intellectual disability and facial dysmorphisms.

PMID:33350388 reported nine patients from seven unrelated families identified with variants in KDM5A, of which three unrelated patients harboured heterozygous variants, while six patients from four unrelated families had homozygous variants. These patients presented with autism spectrum disorder (ASD) and a spectrum of neurodevelopmental phenotypes including intellectual disability, lack of speech, developmental delay and motor impairment.

In addition, loss of KDM5A has resulted in repetitive behaviors, sociability deficits, cognitive dysfunction, and abnormal dendritic morphogenesis in mice.; to: PMID:21937992 reported a family with recessive missense KDM5A variant presenting with an undefined developmental disorder characterised with intellectual disability and facial dysmorphisms.

PMID:33350388 reported nine patients from seven unrelated families identified with variants in KDM5A, of which three unrelated patients harboured heterozygous variants, while six patients from four unrelated families had homozygous variants. These patients presented with autism spectrum disorder (ASD) and a spectrum of neurodevelopmental phenotypes including intellectual disability, lack of speech, developmental delay and motor impairment.

In addition, loss of KDM5A has resulted in repetitive behaviors, sociability deficits, cognitive dysfunction, and abnormal dendritic morphogenesis in mice.

This gene has already been associated with phenotype in Gene2Phenotype (biallelic inheritance with 'limited' rating), but not in OMIM.
Adult onset neurodegenerative disorder v4.11 GBE1 Sarah Leigh Classified gene: GBE1 as Amber List (moderate evidence)
Adult onset neurodegenerative disorder v4.11 GBE1 Sarah Leigh Gene: gbe1 has been classified as Amber List (Moderate Evidence).
Adult onset neurodegenerative disorder v4.10 SS18L1 Sarah Leigh Tag Q2_23_promote_green tag was added to gene: SS18L1.
Intellectual disability v5.24 KDM5A Achchuthan Shanmugasundram Classified gene: KDM5A as Amber List (moderate evidence)
Intellectual disability v5.24 KDM5A Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Tracy Lester (Genetics laboratory, Oxford UK), there is sufficient evidence for this gene to be promoted to GREEN in the next major review.

This gene can be associated with both monoallelic and biallelic inheritance as there are at least three cases each for both of them.
Intellectual disability v5.24 KDM5A Achchuthan Shanmugasundram Gene: kdm5a has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.23 KDM5A Achchuthan Shanmugasundram changed review comment from: PMID:21937992 reported a family with recessive missense KDM5A variant presenting with an undefined developmental disorder characterised with intellectual disability and facial dysmorphisms.

PMID:33350388 reported nine patients from seven unrelated families identified with variants in KDM5A, of which three unrelated patients harboured heterozygous variants, while six patients from four unrelated families had homozygous variants. These patients presented with autism spectrum disorder (ASD) and a spectrum of neurodevelopmental phenotypes including intellectual disability, lack of speech, developmental delay and motor impairment.; to: PMID:21937992 reported a family with recessive missense KDM5A variant presenting with an undefined developmental disorder characterised with intellectual disability and facial dysmorphisms.

PMID:33350388 reported nine patients from seven unrelated families identified with variants in KDM5A, of which three unrelated patients harboured heterozygous variants, while six patients from four unrelated families had homozygous variants. These patients presented with autism spectrum disorder (ASD) and a spectrum of neurodevelopmental phenotypes including intellectual disability, lack of speech, developmental delay and motor impairment.

In addition, loss of KDM5A has resulted in repetitive behaviors, sociability deficits, cognitive dysfunction, and abnormal dendritic morphogenesis in mice.
Adult onset neurodegenerative disorder v4.10 SS18L1 Sarah Leigh Classified gene: SS18L1 as Amber List (moderate evidence)
Adult onset neurodegenerative disorder v4.10 SS18L1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Adult onset neurodegenerative disorder v4.10 SS18L1 Sarah Leigh Gene: ss18l1 has been classified as Amber List (Moderate Evidence).
Adult onset neurodegenerative disorder v4.9 SS18L1 Sarah Leigh reviewed gene: SS18L1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v5.23 KDM5A Achchuthan Shanmugasundram Publications for gene: KDM5A were set to 21937992; 33350388
Intellectual disability v5.22 KDM5A Achchuthan Shanmugasundram Publications for gene: KDM5A were set to 21937992; 33350388
Intellectual disability v5.23 KDM5A Achchuthan Shanmugasundram Publications for gene: KDM5A were set to 21937992; 33350388
Intellectual disability v5.22 KDM5A Achchuthan Shanmugasundram Publications for gene: KDM5A were set to 21937992; 33350388
Intellectual disability v5.22 KDM5A Achchuthan Shanmugasundram Publications for gene: KDM5A were set to 21937992; 33350388
Intellectual disability v5.22 KDM5A Achchuthan Shanmugasundram Publications for gene: KDM5A were set to 21937992; 33350388
Intellectual disability v5.22 KDM5A Achchuthan Shanmugasundram Publications for gene: KDM5A were set to 21937992; 33350388
Intellectual disability v5.22 KDM5A Achchuthan Shanmugasundram Publications for gene: KDM5A were set to 21937992; 33350388
Intellectual disability v5.22 KDM5A Achchuthan Shanmugasundram Publications for gene: KDM5A were set to 21937992; 33350388
Intellectual disability v5.22 KDM5A Achchuthan Shanmugasundram Publications for gene: KDM5A were set to 21937992; 33350388
Intellectual disability v5.22 KDM5A Achchuthan Shanmugasundram Publications for gene: KDM5A were set to 21937992; 33350388
Intellectual disability v5.22 KDM5A Achchuthan Shanmugasundram Publications for gene: KDM5A were set to 21937992; 33350388
Intellectual disability v5.22 KDM5A Achchuthan Shanmugasundram Publications for gene: KDM5A were set to 21937992; 33350388
Intellectual disability v5.22 KDM5A Achchuthan Shanmugasundram Publications for gene: KDM5A were set to 21937992; 33350388
Intellectual disability v5.22 KDM5A Achchuthan Shanmugasundram Publications for gene: KDM5A were set to 21937992; 33350388
Intellectual disability v5.21 KDM5A Achchuthan Shanmugasundram Publications for gene: KDM5A were set to 21937992
Intellectual disability v5.21 KDM5A Achchuthan Shanmugasundram Mode of inheritance for gene: KDM5A was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v5.21 KDM5A Achchuthan Shanmugasundram Mode of inheritance for gene: KDM5A was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v5.21 KDM5A Achchuthan Shanmugasundram Mode of inheritance for gene: KDM5A was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v5.20 KDM5A Achchuthan Shanmugasundram Mode of inheritance for gene: KDM5A was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v5.20 KDM5A Achchuthan Shanmugasundram Mode of inheritance for gene: KDM5A was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v5.19 KDM5A Achchuthan Shanmugasundram changed review comment from: PMID:21937992 reported a family with recessive missense KDM5A variant presenting with an undefined developmental disorder characterised with intellectual disability and facial dysmorphisms.

PMID:33350388 reported nine patients from seven unrelated families identified with variants in KDM5A, of which three unrelated patients harboured heterozygous variants, while six patients from four unrelated families had homozygous variants. These patients presented with autism spectrum disorder (ASD) and a spectrum of neurodevelopmental phenotypes including intellectual disability, lack of speech and developmental delay.; to: PMID:21937992 reported a family with recessive missense KDM5A variant presenting with an undefined developmental disorder characterised with intellectual disability and facial dysmorphisms.

PMID:33350388 reported nine patients from seven unrelated families identified with variants in KDM5A, of which three unrelated patients harboured heterozygous variants, while six patients from four unrelated families had homozygous variants. These patients presented with autism spectrum disorder (ASD) and a spectrum of neurodevelopmental phenotypes including intellectual disability, lack of speech, developmental delay and motor impairment.
Intellectual disability v5.19 KDM5A Achchuthan Shanmugasundram reviewed gene: KDM5A: Rating: GREEN; Mode of pathogenicity: None; Publications: 21937992, 33350388; Phenotypes: autism spectrum disorder, MONDO:0005258, intellectual disability, MONDO:0001071; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder v3.3 SPG7 Sarah Leigh commented on gene: SPG7
Childhood onset dystonia, chorea or related movement disorder v3.3 SPG7 Sarah Leigh Mode of inheritance for gene: SPG7 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v3.10 SPG7 Sarah Leigh Publications for gene: SPG7 were set to
Hereditary neuropathy or pain disorder v3.9 SPG7 Sarah Leigh changed review comment from: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form) autosomal or pseudoautosomal; to: Associated with OMIM:607259 and as definitive Gen2Phen gene for the same condition. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form) autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v3.9 SPG7 Sarah Leigh commented on gene: SPG7
Hereditary neuropathy or pain disorder v3.9 SPG7 Sarah Leigh Mode of inheritance for gene: SPG7 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Retinal disorders v4.7 SPG7 Sarah Leigh Classified gene: SPG7 as Amber List (moderate evidence)
Retinal disorders v4.7 SPG7 Sarah Leigh Gene: spg7 has been classified as Amber List (Moderate Evidence).
Retinal disorders v4.6 SPG7 Sarah Leigh reviewed gene: SPG7: Rating: AMBER; 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
Ataxia and cerebellar anomalies - narrow panel v4.7 SPG7 Sarah Leigh Deleted their comment
Monogenic hearing loss v4.6 LMX1A Achchuthan Shanmugasundram Publications for gene: LMX1A were set to 29754270; 29971487; 32840933; 19540218; 18985389
Hereditary neuropathy or pain disorder v3.8 IGHMBP2 Achchuthan Shanmugasundram Publications for gene: IGHMBP2 were set to 26392352; 34726235
Retinal disorders v4.6 SPG7 Sarah Leigh Mode of inheritance for gene: SPG7 was changed from to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Hereditary ataxia with onset in adulthood v4.8 SPG7 Sarah Leigh reviewed gene: SPG7: Rating: ; 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
Ataxia and cerebellar anomalies - narrow panel v4.7 SPG7 Sarah Leigh commented on gene: SPG7: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form) autosomal or pseudoautosomal.
Hereditary ataxia with onset in adulthood v4.8 SPG7 Sarah Leigh Publications for gene: SPG7 were set to 25681447
Hereditary ataxia with onset in adulthood v4.7 SPG7 Sarah Leigh Tag Q2_23_MOI tag was added to gene: SPG7.
Mitochondrial disorders v4.3 SPG7 Sarah Leigh Publications for gene: SPG7 were set to
Mitochondrial disorders v4.2 SPG7 Sarah Leigh Tag Q2_23_MOI tag was added to gene: SPG7.
Mitochondrial disorders v4.2 SPG7 Sarah Leigh reviewed gene: SPG7: Rating: ; 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
Intellectual disability v5.19 SPG7 Sarah Leigh commented on gene: SPG7
Intellectual disability v5.19 SPG7 Sarah Leigh Publications for gene: SPG7 were set to 22571692
Intellectual disability v5.18 SPG7 Sarah Leigh Mode of inheritance for gene: SPG7 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Hereditary neuropathy v1.465 SPG7 Sarah Leigh commented on gene: SPG7
Hereditary neuropathy v1.465 SPG7 Sarah Leigh Publications for gene: SPG7 were set to
Hereditary neuropathy v1.464 SPG7 Sarah Leigh Mode of inheritance for gene: SPG7 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Possible mitochondrial disorder - nuclear genes v3.3 SPG7 Sarah Leigh commented on gene: SPG7
Possible mitochondrial disorder - nuclear genes v3.3 SPG7 Sarah Leigh Publications for gene: SPG7 were set to 24727571
Likely inborn error of metabolism v4.3 SPG7 Sarah Leigh Tag Q2_23_MOI tag was added to gene: SPG7.
Likely inborn error of metabolism v4.3 SPG7 Sarah Leigh Publications for gene: SPG7 were set to 27604308
Likely inborn error of metabolism v4.2 SPG7 Sarah Leigh edited their review of gene: SPG7: Added comment: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form) autosomal or pseudoautosomal.; Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Undiagnosed metabolic disorders v1.575 SPG7 Sarah Leigh Publications for gene: SPG7 were set to 27604308
Undiagnosed metabolic disorders v1.574 SPG7 Sarah Leigh Mode of inheritance for gene: SPG7 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Undiagnosed metabolic disorders v1.573 SPG7 Sarah Leigh edited their review of gene: SPG7: Added comment: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form) autosomal or pseudoautosomal.; Changed rating: GREEN; Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Adult onset neurodegenerative disorder v4.9 SPG7 Sarah Leigh edited their review of gene: SPG7: Changed publications to: 9635427, 16534102, 17646629, 18200586, 20186691, 22571692
Adult onset neurodegenerative disorder v4.9 SPG7 Sarah Leigh changed review comment from: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form) autosomal or pseudoautosomal.; to: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be both monoallelic and biallelic, autosomal or pseudoautosomal.
Adult onset neurodegenerative disorder v4.9 SPG7 Sarah Leigh edited their review of gene: SPG7: Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Adult onset neurodegenerative disorder v4.9 SPG7 Sarah Leigh changed review comment from: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be both monoallelic and biallelic, autosomal or pseudoautosomal.; to: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form) autosomal or pseudoautosomal.
Adult onset neurodegenerative disorder v4.9 SPG7 Sarah Leigh Mode of inheritance for gene: SPG7 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Adult onset hereditary spastic paraplegia v3.3 SPG7 Sarah Leigh Publications for gene: SPG7 were set to
Adult onset hereditary spastic paraplegia v3.2 SPG7 Sarah Leigh Tag Q2_23_MOI tag was added to gene: SPG7.
Adult onset hereditary spastic paraplegia v3.2 SPG7 Sarah Leigh reviewed gene: SPG7: Rating: ; Mode of pathogenicity: None; Publications: 9635427, 16534102, 17646629, 18200586, 20186691, 22571692; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia v4.4 SPG7 Sarah Leigh reviewed gene: SPG7: Rating: ; 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
Childhood onset hereditary spastic paraplegia v4.4 SPG7 Sarah Leigh Tag Q2_23_MOI tag was added to gene: SPG7.
Childhood onset hereditary spastic paraplegia v4.4 SPG7 Sarah Leigh Publications for gene: SPG7 were set to 9635427
Hereditary spastic paraplegia v1.308 SPG7 Sarah Leigh changed review comment from: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be BOTH monoallelic and biallelic, autosomal or pseudoautosomal.; to: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal.
Hereditary spastic paraplegia v1.308 SPG7 Sarah Leigh edited their review of gene: SPG7: Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Hereditary spastic paraplegia v1.308 SPG7 Sarah Leigh Mode of inheritance for gene: SPG7 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Inherited white matter disorders v1.173 SPG7 Sarah Leigh changed review comment from: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be BOTH monoallelic and biallelic, autosomal or pseudoautosomal.; to: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal.
Inherited white matter disorders v1.173 SPG7 Sarah Leigh edited their review of gene: SPG7: Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Inherited white matter disorders v1.173 SPG7 Sarah Leigh Mode of inheritance for gene: SPG7 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mitochondrial DNA maintenance disorder v3.3 SPG7 Sarah Leigh Tag Q2_23_MOI was removed from gene: SPG7.
Mitochondrial DNA maintenance disorder v3.3 SPG7 Sarah Leigh changed review comment from: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form).; to: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal.
Ataxia and cerebellar anomalies - narrow panel v4.7 SPG7 Sarah Leigh changed review comment from: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form).; to: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form) autosomal or pseudoautosomal.