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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.
Hereditary ataxia v1.321 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
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, 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).
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, 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).
Mitochondrial DNA maintenance disorder v3.3 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
Ataxia and cerebellar anomalies - narrow panel v4.7 SPG7 Sarah Leigh edited their review of gene: SPG7: Changed publications to: 9635427, 16534102, 17646629, 18200586, 20186691, 22571692; Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Hereditary spastic paraplegia v1.307 SPG7 Sarah Leigh Mode of inheritance for gene: SPG7 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary spastic paraplegia v1.306 SPG7 Sarah Leigh Publications for gene: SPG7 were set to Casari et al (1998)
Hereditary spastic paraplegia v1.305 SPG7 Sarah Leigh reviewed gene: SPG7: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mitochondrial DNA maintenance disorder v3.3 SPG7 Sarah Leigh Publications for gene: SPG7 were set to 24727571
Mitochondrial DNA maintenance disorder v3.2 SPG7 Sarah Leigh Tag Q2_23_MOI tag was added to gene: SPG7.
Mitochondrial DNA maintenance disorder v3.2 SPG7 Sarah Leigh reviewed gene: SPG7: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Inherited white matter disorders v1.172 SPG7 Sarah Leigh Publications for gene: SPG7 were set to 22571692, 17646629
Inherited white matter disorders v1.171 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, autosomal or pseudoautosomal.
Inherited white matter disorders v1.171 SPG7 Sarah Leigh edited their review of gene: SPG7: Changed rating: GREEN; Changed publications to: 9635427, 16534102, 17646629, 18200586, 20186691, 22571692; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Inherited white matter disorders v1.171 SPG7 Sarah Leigh Classified gene: SPG7 as Green List (high evidence)
Inherited white matter disorders v1.171 SPG7 Sarah Leigh Gene: spg7 has been classified as Green List (High Evidence).
Hereditary ataxia v1.320 SPG7 Sarah Leigh Publications for gene: SPG7 were set to PMID: 25681447
Hereditary ataxia v1.319 SPG7 Sarah Leigh Mode of inheritance for gene: SPG7 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary ataxia v1.318 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, 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, 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.
Ataxia and cerebellar anomalies - narrow panel v4.7 SPG7 Sarah Leigh Tag Q2_23_MOI tag was added to gene: SPG7.
Ataxia and cerebellar anomalies - narrow panel v4.7 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, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.7 SPG7 Sarah Leigh Publications for gene: SPG7 were set to 25681447; 32893728; 33774748; 32161564; 31068484; 23065789; 9635427; 16534102; 17646629; 18200586, 20186691; 22571692
Ataxia and cerebellar anomalies - narrow panel v4.6 SPG7 Sarah Leigh Publications for gene: SPG7 were set to 25681447; 32893728
White matter disorders and cerebral calcification - narrow panel v3.3 SPG7 Sarah Leigh Publications for gene: SPG7 were set to 22571692, 17646629
Adult onset neurodegenerative disorder v4.8 SPG7 Sarah Leigh edited their review of gene: SPG7: Changed publications to: 9635427, 16534102, 17646629, 18200586, 20186691, 22571692
Adult onset neurodegenerative disorder v4.8 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, autosomal or pseudoautosomal.
Adult onset neurodegenerative disorder v4.8 SPG7 Sarah Leigh Publications for gene: SPG7 were set to 25681447; 16765570; 19364936; 9635427; 18200586
Adult onset neurodegenerative disorder v4.7 SPG7 Sarah Leigh Tag Q2_23_promote_green tag was added to gene: SPG7.
Tag Q2_23_MOI tag was added to gene: SPG7.
Adult onset neurodegenerative disorder v4.7 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, autosomal or pseudoautosomal.; Changed rating: GREEN; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Adult onset neurodegenerative disorder v4.7 SPG7 Sarah Leigh Publications for gene: SPG7 were set to 25681447; 16765570; 19364936; 9635427
Adult onset neurodegenerative disorder v4.6 SPG7 Sarah Leigh Classified gene: SPG7 as Amber List (moderate evidence)
Adult onset neurodegenerative disorder v4.6 SPG7 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 v4.6 SPG7 Sarah Leigh Gene: spg7 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v3.2 SPG7 Sarah Leigh Phenotypes for gene: SPG7 were changed from Spastic paraplegia 7, 607259 to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
Hereditary neuropathy or pain disorder v3.7 SPG7 Sarah Leigh Phenotypes for gene: SPG7 were changed from Hereditary Neuropathies; Spastic paraplegia, optic atrophy, ataxia and sensory-motor axonal neuropathy in some patients to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
Retinal disorders v4.5 SPG7 Sarah Leigh Phenotypes for gene: SPG7 were changed from to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
Hereditary ataxia with onset in adulthood v4.7 SPG7 Sarah Leigh Phenotypes for gene: SPG7 were changed from Spastic paraplegia 7 (#607259) complex forms of the disease. Actually associated with a range of phenotypes including adult-onset ataxia; Autosomal recessive spastic paraplegia 7, 607259 to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
Mitochondrial disorders v4.2 SPG7 Sarah Leigh Phenotypes for gene: SPG7 were changed from Disorders of mitochondrial DNA maintenance and integrity; Spastic paraplegia 7, autosomal recessive, 607259 to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
Intellectual disability v5.17 SPG7 Sarah Leigh Phenotypes for gene: SPG7 were changed from Spastic paraplegia 7, autosomal recessive, 607259 to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
Likely inborn error of metabolism v4.2 SPG7 Sarah Leigh Added comment: Comment on phenotypes: Miscellaneous disorders/unknown function (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Spastic paraplegia 7, autosomal recessive, 607259;Disorders of mitochondrial DNA maintenance and integrity
Likely inborn error of metabolism v4.2 SPG7 Sarah Leigh Phenotypes for gene: SPG7 were changed from Miscellaneous disorders/unknown function (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Spastic paraplegia 7, autosomal recessive, 607259; Disorders of mitochondrial DNA maintenance and integrity to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
Hereditary neuropathy v1.463 SPG7 Sarah Leigh Phenotypes for gene: SPG7 were changed from Hereditary Neuropathies; Spastic paraplegia, optic atrophy, ataxia and sensory-motor axonal neuropathy in some patients to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
Possible mitochondrial disorder - nuclear genes v3.2 SPG7 Sarah Leigh Phenotypes for gene: SPG7 were changed from Progressive external ophthalmoplegia with mitochondrial DNA deletions to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
Undiagnosed metabolic disorders v1.573 SPG7 Sarah Leigh Added comment: Comment on phenotypes: Miscellaneous disorders/unknown function (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Disorders of mitochondrial DNA maintenance and integrity
Undiagnosed metabolic disorders v1.573 SPG7 Sarah Leigh Phenotypes for gene: SPG7 were changed from Miscellaneous disorders/unknown function (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Disorders of mitochondrial DNA maintenance and integrity; Spastic paraplegia 7, autosomal recessive, 607259 to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
Adult onset hereditary spastic paraplegia v3.2 SPG7 Sarah Leigh Phenotypes for gene: SPG7 were changed from Spastic paraplegia 7, autosomal recessive, 607259 to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
Childhood onset hereditary spastic paraplegia v4.3 SPG7 Sarah Leigh Phenotypes for gene: SPG7 were changed from Spastic paraplegia 7, autosomal recessive, 607259 to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
Hereditary spastic paraplegia v1.305 SPG7 Sarah Leigh Phenotypes for gene: SPG7 were changed from Spastic paraplegia 7, autosomal recessive to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
Mitochondrial DNA maintenance disorder v3.2 SPG7 Sarah Leigh Phenotypes for gene: SPG7 were changed from Progressive external ophthalmoplegia with mitochondrial DNA deletions to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
Inherited white matter disorders v1.170 SPG7 Sarah Leigh Phenotypes for gene: SPG7 were changed from Spastic paraplegia 7, autosomal recessive, MIM#607259 to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
Hereditary ataxia v1.318 SPG7 Sarah Leigh Phenotypes for gene: SPG7 were changed from Spastic paraplegia 7 (#607259) complex forms of the disease. Actually associated with a range of phenotypes including adult-onset ataxia to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
Ataxia and cerebellar anomalies - narrow panel v4.5 SPG7 Sarah Leigh Phenotypes for gene: SPG7 were changed from Spastic paraplegia 7, autosomal recessive, OMIM:607259 to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
White matter disorders and cerebral calcification - narrow panel v3.2 SPG7 Sarah Leigh Phenotypes for gene: SPG7 were changed from Spastic paraplegia 7, autosomal recessive, MIM#607259 to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
Adult onset neurodegenerative disorder v4.5 SPG7 Sarah Leigh Phenotypes for gene: SPG7 were changed from Spastic paraplegia 7 (#607259) complex forms of the disease. Actually associated with a range of phenotypes including adult-onset ataxia; Spastic paraplegia 7, autosomal recessive to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
Adult onset neurodegenerative disorder v4.4 SPG7 Sarah Leigh Publications for gene: SPG7 were set to PMID: 25681447; Casari et al (1998)
Paediatric or syndromic cardiomyopathy v3.4 RRAGC Hannah Robinson gene: RRAGC was added
gene: RRAGC was added to Paediatric or syndromic cardiomyopathy. Sources: NHS GMS,Literature
Mode of inheritance for gene: RRAGC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RRAGC were set to 27234373
Penetrance for gene: RRAGC were set to unknown
Review for gene: RRAGC was set to GREEN
gene: RRAGC was marked as current diagnostic
Added comment: Newborn patient reported with syndromic DCM ventricular dilation and systolic dysfunction, bilateral cataracts, and mild facial dysmorphisms with de novo missense variant in RRAGC (PMID: 27234373). Subsequently, three unrelated patients reported with de novo variants in this gene displayed DCM and hepatopathy, plus brain anomalies including pachygyria,
polymicrogyria, and septo-optic dysplasia (https://doi.org/10.1016/j.gim.2023.100838, PMID not yet available). Additional patient identified through R14 WGS in Exeter Genomics Laboratory.
Sources: NHS GMS, Literature
Hypertrophic cardiomyopathy v4.1 TULP3 John Sayer gene: TULP3 was added
gene: TULP3 was added to Hypertrophic cardiomyopathy. Sources: Expert list
Mode of inheritance for gene: TULP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TULP3 were set to 35397207
Phenotypes for gene: TULP3 were set to hypertrophic cardiomyopathy; cystic kidney disease; congenital hepatic fibrosis
Penetrance for gene: TULP3 were set to Complete
Review for gene: TULP3 was set to RED
Added comment: 3 cases of hypertrophic cardiomyopathy reported by Devane et al. PMID 35397207
Sources: Expert list
Ductal plate malformation v1.19 TULP3 John Sayer gene: TULP3 was added
gene: TULP3 was added to Ductal plate malformation. Sources: Expert list
Mode of inheritance for gene: TULP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TULP3 were set to 36460032; 36276950; 35397207
Phenotypes for gene: TULP3 were set to cystic kidney disease; ductal plate malformation; congentital hepatic fibrosis; cardiomyopathy
Penetrance for gene: TULP3 were set to Complete
Review for gene: TULP3 was set to GREEN
Added comment: Congenital hepatic fibrosis and ductal plate malformation is a common phenotype
See OMIM 604730
Sources: Expert list
Cystic kidney disease v4.1 TULP3 John Sayer gene: TULP3 was added
gene: TULP3 was added to Cystic kidney disease. Sources: Expert list
Mode of inheritance for gene: TULP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TULP3 were set to 36460032; 36276950; 35397207
Phenotypes for gene: TULP3 were set to cystic kidney disease; ductal plate malformation; congentital hepatic fibrosis; cardiomyopathy
Penetrance for gene: TULP3 were set to Complete
Review for gene: TULP3 was set to GREEN
Added comment: TULP3 is a novel human cilipathy gene (OMIM 604730)
Hepatorenocardiac degenerative fibrosis is OMIM pehnotype
Cystic kidney disease is a typical feature
Sources: Expert list
Adult onset neurodegenerative disorder v4.3 SPG21 Sarah Leigh edited their review of gene: SPG21: 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 (PMIDs: 14564668, 24451228, 28752238), together with a supportive mouse model (PMID: 26978163).; Changed rating: GREEN
Adult onset leukodystrophy v3.2 SPG21 Sarah Leigh edited their review of gene: SPG21: 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 (PMIDs: 14564668, 24451228, 28752238), together with a supportive mouse model (PMID: 26978163).; Changed rating: GREEN
Adult onset leukodystrophy v3.2 SPG21 Sarah Leigh Tag Q2_23_promote_green tag was added to gene: SPG21.
Adult onset neurodegenerative disorder v4.3 SPG21 Sarah Leigh Tag Q2_23_promote_green tag was added to gene: SPG21.
Adult onset leukodystrophy v3.2 SPG21 Sarah Leigh Classified gene: SPG21 as Amber List (moderate evidence)
Adult onset leukodystrophy v3.2 SPG21 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 leukodystrophy v3.2 SPG21 Sarah Leigh Gene: spg21 has been classified as Amber List (Moderate Evidence).
Adult onset neurodegenerative disorder v4.3 SPG21 Sarah Leigh Classified gene: SPG21 as Amber List (moderate evidence)
Adult onset neurodegenerative disorder v4.3 SPG21 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 v4.3 SPG21 Sarah Leigh Gene: spg21 has been classified as Amber List (Moderate Evidence).
Adult onset neurodegenerative disorder v4.2 SPG21 Sarah Leigh Publications for gene: SPG21 were set to 14564668; 28752238; 24451228
Paediatric or syndromic cardiomyopathy v3.4 TBX20 Achchuthan Shanmugasundram Tag Q2_23_NHS_review tag was added to gene: TBX20.
Paediatric or syndromic cardiomyopathy v3.4 TBX20 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: TBX20.
Paediatric or syndromic cardiomyopathy v3.4 TBX20 Achchuthan Shanmugasundram changed review comment from: One of the patients reported in PMID:30384889 was identified with an autosomal dominant variant in TBX20 (p.M224V) and was presented with left ventricular noncompaction (LVNC) cardiomyopathy and IgA deficiency. The age of onset of LVNC in this patient was 9 years of age.

PMID:35282022 reported a 6 year old patient with LVNC identified with a de novo variant (p.Arg287Trp) in TBX20 gene.

PMID:17668378 reported two families with congenital heart defects, in which affected individuals carried heterozygous variants in TBX20 gene. Individuals from one of these families (with p.Gln195Ter variant) presented with dilated cardiomyopathy in addition to congenital heart defects.; to: One of the patients reported in PMID:30384889 was identified with an autosomal dominant variant in TBX20 (p.M224V) and was presented with left ventricular noncompaction (LVNC) cardiomyopathy and IgA deficiency. The age of onset of LVNC in this patient was 9 years of age. PMID:35282022 reported a 6 year old patient with LVNC identified with a de novo variant (p.Arg287Trp) in TBX20 gene. These two cases fit well with paediatric cardiomyopathy as both cases are of childhood onset (<12 years of age at onset).

In addition to cases reviewed by Matthew Edwards, PMID:17668378 also reported two families with congenital heart defects, in which affected individuals carried heterozygous variants in TBX20 gene. Individuals from one of these families (with p.Gln195Ter variant) presented with dilated cardiomyopathy in addition to congenital heart defects. All these cases with wide spectrum of phenotypes including cardiomyopathy and congenital hart defects fits well with syndromic cardiomyopathy.
Intellectual disability v5.16 SPTAN1 Sarah Leigh Phenotypes for gene: SPTAN1 were changed from Epileptic encephalopathy, early infantile, 5, 613477; EPILEPTIC ENCEPHALOPATHY EARLY INFANTILE TYPE 5 (EIEE5) to Developmental and epileptic encephalopathy 5, OMIM:613477; developmental and epileptic encephalopathy, 5, MONDO:0013277
Paediatric or syndromic cardiomyopathy v3.4 TBX20 Achchuthan Shanmugasundram Classified gene: TBX20 as Amber List (moderate evidence)
Paediatric or syndromic cardiomyopathy v3.4 TBX20 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be associated with paediatric or syndromic cardiomyopathy and hence should be promoted to green at the next major review.
Paediatric or syndromic cardiomyopathy v3.4 TBX20 Achchuthan Shanmugasundram Gene: tbx20 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.15 SPTAN1 Sarah Leigh Publications for gene: SPTAN1 were set to
Paediatric or syndromic cardiomyopathy v3.3 TBX20 Achchuthan Shanmugasundram Publications for gene: TBX20 were set to PMID: 33585493; PMID: 275101702, PMID: 28798025; PMID: 32600061, PMID: 22080862
Paediatric or syndromic cardiomyopathy v3.2 TBX20 Achchuthan Shanmugasundram Phenotypes for gene: TBX20 were changed from Cardiomyopathy, dilated with or without LVNC; Atrial septal defect, congential heart disease to Atrial septal defect 4, OMIM:611363; Cardiomyopathy, dilated with or without LVNC; Atrial septal defect, congential heart disease
Paediatric or syndromic cardiomyopathy v3.1 TBX20 Achchuthan Shanmugasundram edited their review of gene: TBX20: Changed phenotypes to: Atrial septal defect 4, OMIM:611363
Paediatric or syndromic cardiomyopathy v3.1 TBX20 Achchuthan Shanmugasundram edited their review of gene: TBX20: Changed rating: GREEN
Paediatric or syndromic cardiomyopathy v3.1 TBX20 Achchuthan Shanmugasundram reviewed gene: TBX20: Rating: ; Mode of pathogenicity: None; Publications: 17668378, 30384889, 35282022; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v3.1 AARS2 Patrick Campbell gene: AARS2 was added
gene: AARS2 was added to Fetal anomalies. Sources: NHS GMS
Mode of inheritance for gene: AARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AARS2 were set to 30819764
Phenotypes for gene: AARS2 were set to fetal hydrops; polyhydramnios; pulmonary effusion; cardiomyopathy
Penetrance for gene: AARS2 were set to Complete
Mode of pathogenicity for gene: AARS2 was set to Other
Review for gene: AARS2 was set to GREEN
Added comment: This gene is not on R21. It can cause fetal phenotype and early neonatal death with bi-allelic variants. We had a fetus present locally with fetal hydrops from around 28 weeks. The result was discovered on whole genome sequencing after miscarriage (R14). It would not have been identified on R21 for fetal anomalies. The local finding of presentation antenatally is corroborated by recent publication (PMID 30819764) with a case showing polyhydramnios and nonimmune hydrops, with small pulmonary effusions and significant ascites first detected at 35 wk of pregnancy.
Consideration should be given to adding the gene to R21.
Sources: NHS GMS
Retinal disorders v4.4 SGSH 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 review. These include at least four cases with retinal disorders in literature and additional two cases reported by Siying Lin (Moorfields Eye Hospital).; to: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next major review. These include at least four unrelated cases with retinal disorders in literature and additional two cases reported by Siying Lin (Moorfields Eye Hospital).
Retinal disorders v4.4 SGSH Achchuthan Shanmugasundram Classified gene: SGSH as Amber List (moderate evidence)
Retinal disorders v4.4 SGSH 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. These include at least four cases with retinal disorders in literature and additional two cases reported by Siying Lin (Moorfields Eye Hospital).
Retinal disorders v4.4 SGSH Achchuthan Shanmugasundram Gene: sgsh has been classified as Amber List (Moderate Evidence).
Retinal disorders v4.3 SGSH Achchuthan Shanmugasundram Phenotypes for gene: SGSH were changed from to Retinal dystrophy, HP:0000556; retinitis pigmentosa, MONDO:0019200
Retinal disorders v4.2 SGSH Achchuthan Shanmugasundram Publications for gene: SGSH were set to PMID 31718697
Retinal disorders v4.1 SGSH Achchuthan Shanmugasundram edited their review of gene: SGSH: Changed publications to: 31718697, 32195255
Retinal disorders v4.1 SGSH Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: SGSH.
Tag Q2_23_NHS_review tag was added to gene: SGSH.
Retinal disorders v4.1 SGSH Achchuthan Shanmugasundram changed review comment from: PMID:31718697 reported that patients from three unrelated families with Mucopolysaccharidosis type III (MPS-III) presented with retinal dystrophy and another unrelated patient was presented with retinitis pigmentosa. They were identified with compound heterozygous variants in SGSH gene.

In addition, MPS-IIIA mice exhibited a progressive retinal dystrophy characterized by significant alterations in visual function (PMID:32195255).

Although SGSH gene has already been associated with MPS-IIIA in both OMIM and Gene2Phenotype, retinal phenotypes have not yet been included in these records.; to: PMID:31718697 reported that patients from three unrelated families with Mucopolysaccharidosis type III (MPS-III) presented with retinal dystrophy and another unrelated patient was presented with retinitis pigmentosa. They were identified with compound heterozygous variants in SGSH gene.

Siying Lin (Moorfields Eye Hospital) also reviewed about two additional cases of retinal dystrophy identified with biallelic SGSH variants in their patient cohort.

In addition, MPS-IIIA mice exhibited a progressive retinal dystrophy characterized by significant alterations in visual function (PMID:32195255).

Although SGSH gene has already been associated with MPS-IIIA in both OMIM and Gene2Phenotype, retinal phenotypes have not yet been included in these records.
Retinal disorders v4.1 SGSH Achchuthan Shanmugasundram reviewed gene: SGSH: Rating: GREEN; Mode of pathogenicity: None; Publications: 31718697; Phenotypes: Retinal dystrophy, HP:0000556, retinitis pigmentosa, MONDO:0019200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v3.6 TDP1 Achchuthan Shanmugasundram changed review comment from: As reviewed by Ian Berry (Leeds Genetics Laboratory), there are now three unrelated families reported in literature with Spinocerebellar ataxia with axonal neuropathy-1 (SCAN1) and identified with homozygous variant in TDP1 gene. However, all three families are of Arab descent (one family from Saudi Arabia and two families from Oman) and they presented with the same homozygous variant (p.His493Arg).

This gene has been associated with phenotypes in OMIM (MIM #607250), but not in Gene2Phenotype.; to: As reviewed by Ian Berry (Leeds Genetics Laboratory), there are now three unrelated families reported in literature with Spinocerebellar ataxia with axonal neuropathy-1 (SCAN1) and identified with homozygous variant in TDP1 gene. However, all three families are of Arab descent (one family from Saudi Arabia and two families from Oman) and they presented with the same homozygous variant (p.His493Arg).

There are a number of functional studies characterising the function of H493R variant in vitro (PMIDs:15920477, 17948061 & 31723605).

This gene has been associated with phenotypes in OMIM (MIM #607250), but not in Gene2Phenotype.
Hereditary ataxia with onset in adulthood v4.6 TDP1 Achchuthan Shanmugasundram changed review comment from: As reviewed by Ian Berry (Leeds Genetics Laboratory), there are now three unrelated families reported in literature with Spinocerebellar ataxia with axonal neuropathy-1 (SCAN1) and identified with homozygous variant in TDP1 gene. However, all three families are of Arab descent (one family from Saudi Arabia and two families from Oman) and they presented with the same homozygous variant (p.His493Arg).

There are a number of functional studies characterising the function of H493R variant in vitro (PMIDs:15920477, 17948061 & 31723605)

This gene has been associated with phenotypes in OMIM (MIM #607250), but not in Gene2Phenotype.; to: As reviewed by Ian Berry (Leeds Genetics Laboratory), there are now three unrelated families reported in literature with Spinocerebellar ataxia with axonal neuropathy-1 (SCAN1) and identified with homozygous variant in TDP1 gene. However, all three families are of Arab descent (one family from Saudi Arabia and two families from Oman) and they presented with the same homozygous variant (p.His493Arg).

There are a number of functional studies characterising the function of H493R variant in vitro (PMIDs:15920477, 17948061 & 31723605).

This gene has been associated with phenotypes in OMIM (MIM #607250), but not in Gene2Phenotype.
Hereditary neuropathy or pain disorder v3.6 TDP1 Achchuthan Shanmugasundram edited their review of gene: TDP1: Changed publications to: 12244316, 15920477, 17948061, 31182267, 31723605
Hereditary ataxia with onset in adulthood v4.6 TDP1 Achchuthan Shanmugasundram Publications for gene: TDP1 were set to 12244316; 31182267
Hereditary ataxia with onset in adulthood v4.5 TDP1 Achchuthan Shanmugasundram changed review comment from: As reviewed by Ian Berry (Leeds Genetics Laboratory), there are now three unrelated families reported in literature with Spinocerebellar ataxia with axonal neuropathy-1 (SCAN1) and identified with homozygous variant in TDP1 gene. However, all three families are of Arab descent (one family from Saudi Arabia and two families from Oman) and they presented with the same homozygous variant (p.His493Arg).

This gene has been associated with phenotypes in OMIM (MIM #607250), but not in Gene2Phenotype.; to: As reviewed by Ian Berry (Leeds Genetics Laboratory), there are now three unrelated families reported in literature with Spinocerebellar ataxia with axonal neuropathy-1 (SCAN1) and identified with homozygous variant in TDP1 gene. However, all three families are of Arab descent (one family from Saudi Arabia and two families from Oman) and they presented with the same homozygous variant (p.His493Arg).

There are a number of functional studies characterising the function of H493R variant in vitro (PMIDs:15920477, 17948061 & 31723605)

This gene has been associated with phenotypes in OMIM (MIM #607250), but not in Gene2Phenotype.
Hereditary ataxia with onset in adulthood v4.5 TDP1 Achchuthan Shanmugasundram edited their review of gene: TDP1: Changed publications to: 12244316, 15920477, 17948061, 31182267, 31723605
Hereditary neuropathy or pain disorder v3.6 TDP1 Achchuthan Shanmugasundram Classified gene: TDP1 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v3.6 TDP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene can now be promoted to AMBER as there are three unrelated cases. The "founder-effect" tag has been added as they are all of Middle Eastern descent and harboured the same homozygous variant. Hence, it cannot be promoted to green rating.
Hereditary neuropathy or pain disorder v3.6 TDP1 Achchuthan Shanmugasundram Gene: tdp1 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v3.5 TDP1 Achchuthan Shanmugasundram Publications for gene: TDP1 were set to 12244316; 31182267
Hereditary neuropathy or pain disorder v3.4 TDP1 Achchuthan Shanmugasundram Tag founder-effect tag was added to gene: TDP1.
Hereditary neuropathy or pain disorder v3.4 TDP1 Achchuthan Shanmugasundram Phenotypes for gene: TDP1 were changed from Hereditary Neuropathies to ?Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1, OMIM:607250
Hereditary neuropathy or pain disorder v3.3 TDP1 Achchuthan Shanmugasundram Publications for gene: TDP1 were set to 12244316
Hereditary neuropathy or pain disorder v3.2 TDP1 Achchuthan Shanmugasundram reviewed gene: TDP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 12244316, 31182267; Phenotypes: ?Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1, OMIM:607250; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary ataxia with onset in adulthood v4.5 TDP1 Achchuthan Shanmugasundram Classified gene: TDP1 as Amber List (moderate evidence)
Hereditary ataxia with onset in adulthood v4.5 TDP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene can now be promoted to AMBER as there are three unrelated cases. The "founder-effect" tag has been added as they are all of Middle Eastern descent and harboured the same homozygous variant. Hence, it cannot be promoted to green rating.
Hereditary ataxia with onset in adulthood v4.5 TDP1 Achchuthan Shanmugasundram Gene: tdp1 has been classified as Amber List (Moderate Evidence).
Hereditary ataxia with onset in adulthood v4.4 TDP1 Achchuthan Shanmugasundram Tag founder-effect tag was added to gene: TDP1.
Hereditary ataxia with onset in adulthood v4.4 TDP1 Achchuthan Shanmugasundram Phenotypes for gene: TDP1 were changed from Autosomal recessive spinocerebellar ataxia with axonal neuropathy, 607250; Spinocerebellar ataxia, autosomal recessive with axonal neuropathy to ?Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1, OMIM:607250
Hereditary ataxia with onset in adulthood v4.3 TDP1 Achchuthan Shanmugasundram Publications for gene: TDP1 were set to 12244316; 31182267
Hereditary ataxia with onset in adulthood v4.2 TDP1 Achchuthan Shanmugasundram Publications for gene: TDP1 were set to
Hereditary ataxia with onset in adulthood v4.1 TDP1 Achchuthan Shanmugasundram reviewed gene: TDP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 12244316, 31182267; Phenotypes: ?Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1, OMIM:607250; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital muscular dystrophy v4.9 PYROXD1 Achchuthan Shanmugasundram Deleted their comment
Congenital muscular dystrophy v4.9 PYROXD1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient evidence (>3 unrelated cases) with childhood-onset dystrophy for this gene to be promoted to GREEN in this panel in the next major review.; to: Comment on list classification: There is sufficient evidence (>3 unrelated cases) with childhood-onset muscular dystrophy for this gene to be promoted to GREEN in this panel in the next major review.
Congenital muscular dystrophy v4.9 PYROXD1 Achchuthan Shanmugasundram Tag Q2_23_NHS_review tag was added to gene: PYROXD1.
Congenital muscular dystrophy v4.9 PYROXD1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: PYROXD1.
Congenital muscular dystrophy v4.9 PYROXD1 Achchuthan Shanmugasundram Classified gene: PYROXD1 as Amber List (moderate evidence)
Congenital muscular dystrophy v4.9 PYROXD1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (>3 unrelated cases) with childhood-onset dystrophy for this gene to be promoted to GREEN in this panel in the next major review.
Congenital muscular dystrophy v4.9 PYROXD1 Achchuthan Shanmugasundram Gene: pyroxd1 has been classified as Amber List (Moderate Evidence).
Congenital muscular dystrophy v4.9 PYROXD1 Achchuthan Shanmugasundram Classified gene: PYROXD1 as Amber List (moderate evidence)
Congenital muscular dystrophy v4.9 PYROXD1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (>3 unrelated cases) with childhood-onset dystrophy for this gene to be promoted to GREEN in this panel in the next major review.
Congenital muscular dystrophy v4.9 PYROXD1 Achchuthan Shanmugasundram Gene: pyroxd1 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v4.4 NFASC Sarah Leigh Deleted their comment
Ataxia and cerebellar anomalies - narrow panel v4.4 NFASC Sarah Leigh Deleted their comment
Ataxia and cerebellar anomalies - narrow panel v4.4 NFASC Sarah Leigh Classified gene: NFASC as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v4.4 NFASC Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v4.4 NFASC Sarah Leigh Gene: nfasc has been classified as Amber List (Moderate Evidence).
Congenital muscular dystrophy v4.8 PYROXD1 Achchuthan Shanmugasundram Publications for gene: PYROXD1 were set to 33694278; 30515627
Ataxia and cerebellar anomalies - narrow panel v4.3 NFASC Sarah Leigh Tag Q2_23_promote_green tag was added to gene: NFASC.
Congenital muscular dystrophy v4.8 PYROXD1 Achchuthan Shanmugasundram Publications for gene: PYROXD1 were set to 33694278; 30515627
Congenital muscular dystrophy v4.8 PYROXD1 Achchuthan Shanmugasundram Publications for gene: PYROXD1 were set to PMID: 33694278; 30515627
Ataxia and cerebellar anomalies - narrow panel v4.3 NFASC Sarah Leigh Classified gene: NFASC as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v4.3 NFASC Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v4.3 NFASC Sarah Leigh Gene: nfasc has been classified as Amber List (Moderate Evidence).
Congenital muscular dystrophy v4.7 PYROXD1 Achchuthan Shanmugasundram reviewed gene: PYROXD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33694278; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.2 NFASC Sarah Leigh Entity copied from Hereditary ataxia v1.317
Ataxia and cerebellar anomalies - narrow panel v4.2 NFASC Sarah Leigh gene: NFASC was added
gene: NFASC was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature,Expert Review Green
Mode of inheritance for gene: NFASC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NFASC were set to 30850329; 31608123; 31501903
Phenotypes for gene: NFASC were set to Neurodevelopmental disorder with central and peripheral motor dysfunction, OMIM:618356; neurodevelopmental disorder with central and peripheral motor dysfunction, MONDO:0032698
Penetrance for gene: NFASC were set to Complete
Hereditary ataxia v1.317 NFASC Sarah Leigh edited their review of gene: NFASC: Added comment: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least three variants have been reported in three cases of OMIM:618356, where early onset ataxia is part of the phenotype (PMID: 30850329, 31608123, 31501903).; Changed rating: GREEN
Hereditary ataxia v1.317 NFASC Sarah Leigh Classified gene: NFASC as Green List (high evidence)
Hereditary ataxia v1.317 NFASC Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Hereditary ataxia v1.317 NFASC Sarah Leigh Gene: nfasc has been classified as Green List (High Evidence).
Hereditary ataxia v1.316 NFASC Sarah Leigh Publications for gene: NFASC were set to PMID: 30850329, 31608123, 31501903
Hereditary ataxia v1.315 NFASC Sarah Leigh Phenotypes for gene: NFASC were changed from Cerebellar ataxia, Demyelinating neuropathy to Neurodevelopmental disorder with central and peripheral motor dysfunction, OMIM:618356; neurodevelopmental disorder with central and peripheral motor dysfunction, MONDO:0032698
Intellectual disability v5.14 NFASC Sarah Leigh Phenotypes for gene: NFASC were changed from Neurodevelopmental disorder with central and peripheral motor dysfunction 618356 to Neurodevelopmental disorder with central and peripheral motor dysfunction, OMIM:618356; neurodevelopmental disorder with central and peripheral motor dysfunction, MONDO:003269
Early onset dystonia v1.133 VPS11 Sarah Leigh Classified gene: VPS11 as Amber List (moderate evidence)
Early onset dystonia v1.133 VPS11 Sarah Leigh Gene: vps11 has been classified as Amber List (Moderate Evidence).
Early onset dystonia v1.132 VPS11 Sarah Leigh reviewed gene: VPS11: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Early onset dystonia v1.132 VPS11 Sarah Leigh Phenotypes for gene: VPS11 were changed from Neurodevelopmental disorder; Hypomyelination; Microcephaly; Infantile-onset dystonia; Adult-onset dystonia; Spasticity to ?Dystonia 32, OMIM:619637; dystonia 32, MONDO:0030486
Early onset dystonia v1.131 VPS11 Sarah Leigh Publications for gene: VPS11 were set to PMID: 33452836; 27120463; 27473128; 33871597
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.3 PYROXD1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: PYROXD1.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.3 PYROXD1 Achchuthan Shanmugasundram changed review comment from: PMID:30345904 reported a Sudanese patient of Arab descent identified with homozygous variant (p.Asn155Ser) in PYROXD1 gene and presented with limb-girdle-type muscular dystrophy (LGMD). The variant was present in heterozygous state in unaffected sister, unaffected son and unaffected daughter and absent in unaffected brother.

PMID:30515627 reported four patients from three Finnish families with biallelic variants (three with homozygous p.Asn155Ser variant and one with compound heterozygous p.Asn155Ser/ p.Tyr354Cys variants). All of them presented with an adult-onset slowly-progressive LGMD phenotype of symmetric muscle weakness and wasting.

PMID:33694278 reported three patients from two consanguineous Turkish families with biallelic variants (homozygous missense variant (p.Asn155Ser) in family 1 with two affected females and compound heterozygous variants (p.Asn155Ser/ p.Leu112Valfs*8) in affected male of family 2). They presented with mild LGMD, facial weakness, normal CK levels, and slow progress. Authors report that their data suggest that c.464A>G is a Turkish founder mutation.; to: PMID:30345904 reported a Sudanese patient of Arab descent identified with homozygous variant (p.Asn155Ser) in PYROXD1 gene and presented with limb-girdle-type muscular dystrophy (LGMD). The variant was present in heterozygous state in unaffected sister, unaffected son and unaffected daughter and absent in unaffected brother.

PMID:30515627 reported four patients from three Finnish families with biallelic variants (three with homozygous p.Asn155Ser variant and one with compound heterozygous p.Asn155Ser/ p.Tyr354Cys variants). All of them presented with an adult-onset slowly-progressive LGMD phenotype of symmetric muscle weakness and wasting.

PMID:33694278 reported three patients from two consanguineous Turkish families with biallelic variants (homozygous missense variant (p.Asn155Ser) in family 1 with two affected females and compound heterozygous variants (p.Asn155Ser/ p.Leu112Valfs*8) in affected male of family 2). They presented with mild LGMD, facial weakness, normal CK levels, and slow progress. Authors report that their data suggest that c.464A>G is a Turkish founder mutation.

This gene has not yet been associated with LGMD either in OMIM or in Gene2Phenotype.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.3 PYROXD1 Achchuthan Shanmugasundram changed review comment from: PMID:30515627 reported four patients from three Finnish families with biallelic variants (three with homozygous p.Asn155Ser variant and one with compound heterozygous p.Asn155Ser/ p.Tyr354Cys variants). All of them presented with an adult-onset slowly-progressive limb-girdle-type muscular dystrophy (LGMD) phenotype of symmetric muscle weakness and wasting.

PMID:33694278 reported three patients from two consanguineous Turkish families with biallelic variants (homozygous missense variant (p.Asn155Ser) in family 1 with two affected females and compound heterozygous variants (p.Asn155Ser/ p.Leu112Valfs*8) in affected male of family 2). They presented with mild LGMD, facial weakness, normal CK levels, and slow progress. Authors report that their data suggest that c.464A>G is a Turkish founder mutation.; to: PMID:30345904 reported a Sudanese patient of Arab descent identified with homozygous variant (p.Asn155Ser) in PYROXD1 gene and presented with limb-girdle-type muscular dystrophy (LGMD). The variant was present in heterozygous state in unaffected sister, unaffected son and unaffected daughter and absent in unaffected brother.

PMID:30515627 reported four patients from three Finnish families with biallelic variants (three with homozygous p.Asn155Ser variant and one with compound heterozygous p.Asn155Ser/ p.Tyr354Cys variants). All of them presented with an adult-onset slowly-progressive LGMD phenotype of symmetric muscle weakness and wasting.

PMID:33694278 reported three patients from two consanguineous Turkish families with biallelic variants (homozygous missense variant (p.Asn155Ser) in family 1 with two affected females and compound heterozygous variants (p.Asn155Ser/ p.Leu112Valfs*8) in affected male of family 2). They presented with mild LGMD, facial weakness, normal CK levels, and slow progress. Authors report that their data suggest that c.464A>G is a Turkish founder mutation.
Severe microcephaly v4.3 MED11 Sarah Leigh edited their review of gene: MED11: Changed rating: AMBER
Severe microcephaly v4.3 MED11 Sarah Leigh Tag Q2_23_promote_green was removed from gene: MED11.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.3 PYROXD1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient number of cases (5 unrelated cases) to promote this gene to GREEN at the next major review.

Although the same variant has been identified in all patients reported with homozygous variants, the two patients with compound heterozygous variants harboured this variant together with novel variants.; to: Comment on list classification: There is sufficient number of cases (6 unrelated cases) to promote this gene to GREEN at the next major review.

Although the same variant (p.Asn155Ser) has been identified in all patients reported with homozygous variants, two patients with compound heterozygous variants harboured p.Asn155Ser together with novel variants.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.3 PYROXD1 Achchuthan Shanmugasundram edited their review of gene: PYROXD1: Changed publications to: 30345904, 30515627, 33694278
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.3 PYROXD1 Achchuthan Shanmugasundram Publications for gene: PYROXD1 were set to 30345904; 30515627; 27745833
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.2 PYROXD1 Achchuthan Shanmugasundram Deleted their comment
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.2 PYROXD1 Achchuthan Shanmugasundram Classified gene: PYROXD1 as Amber List (moderate evidence)
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.2 PYROXD1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient number of cases (5 unrelated cases) to promote this gene to GREEN at the next major review.

Although the same variant has been identified in all patients reported with homozygous variants, the two patients with compound heterozygous variants harboured this variant together with novel variants.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.2 PYROXD1 Achchuthan Shanmugasundram Gene: pyroxd1 has been classified as Amber List (Moderate Evidence).
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.2 PYROXD1 Achchuthan Shanmugasundram Classified gene: PYROXD1 as Amber List (moderate evidence)
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.2 PYROXD1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient number of cases (5 unrelated cases) to promote this gene to GREEN at the next major review.

Although the same variant has been identified in all patients reported with homozygous variants, the two patients with compound heterozygous variants harboured this variant together with novel variants.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.2 PYROXD1 Achchuthan Shanmugasundram Gene: pyroxd1 has been classified as Amber List (Moderate Evidence).
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.1 PYROXD1 Achchuthan Shanmugasundram reviewed gene: PYROXD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30515627, 33694278; Phenotypes: limb-girdle muscular dystrophy, MONDO:0016971; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.13 MED11 Sarah Leigh Classified gene: MED11 as Amber List (moderate evidence)
Intellectual disability v5.13 MED11 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 v5.13 MED11 Sarah Leigh Gene: med11 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.6 MED11 Sarah Leigh Classified gene: MED11 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.6 MED11 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Early onset or syndromic epilepsy v4.6 MED11 Sarah Leigh Gene: med11 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v4.3 MED11 Sarah Leigh Classified gene: MED11 as Amber List (moderate evidence)
Severe microcephaly v4.3 MED11 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be amber on the Severe microcephaly panel.
Severe microcephaly v4.3 MED11 Sarah Leigh Gene: med11 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v4.2 MED11 Sarah Leigh gene: MED11 was added
gene: MED11 was added to Severe microcephaly. Sources: Literature
Q2_23_promote_green tags were added to gene: MED11.
Mode of inheritance for gene: MED11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MED11 were set to 36001086
Phenotypes for gene: MED11 were set to MED11-associated neurodevelopmental disorder
Review for gene: MED11 was set to GREEN
Added comment: Not associated with a phenotype in OMIM, but is associated with MED11-associated neurodevelopmental disorder in Gen2Phen. PMID: 36001086 reports a single MED11 variant (NM_001001683.4: c.325C>T, p.Arg109*), that segregates with the condition in five unrelated families, however, there is homozygosity between two of these families, idicating that they may be related. Global delay was observed in three individuals from three unrelated familes and seizures were evident in four individuals from four unrelated families. Severe microcephaly was apparent in the two unrelated familes where this parameter was recorded. Overall, the MED11-associated neurodevelopmental disorder appeared to result in profound effects and proved fatal at birth and 10 days in two of the cases reported.
Sources: Literature
Early onset or syndromic epilepsy v4.5 MED11 Sarah Leigh gene: MED11 was added
gene: MED11 was added to Early onset or syndromic epilepsy. Sources: Literature
Q2_23_promote_green tags were added to gene: MED11.
Mode of inheritance for gene: MED11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MED11 were set to 36001086
Phenotypes for gene: MED11 were set to MED11-associated neurodevelopmental disorder
Review for gene: MED11 was set to GREEN
Added comment: Not associated with a phenotype in OMIM, but is associated with MED11-associated neurodevelopmental disorder in Gen2Phen. PMID: 36001086 reports a single MED11 variant (NM_001001683.4: c.325C>T, p.Arg109*), that segregates with the condition in five unrelated families, however, there is homozygosity between two of these families, idicating that they may be related. Global delay was observed in three individuals from three unrelated familes and seizures were evident in four individuals from four unrelated families. Severe microcephaly was apparent in the two unrelated familes where this parameter was recorded. Overall, the MED11-associated neurodevelopmental disorder appeared to result in profound effects and proved fatal at birth and 10 days in two of the cases reported.
Sources: Literature
Intellectual disability v5.12 MED11 Sarah Leigh gene: MED11 was added
gene: MED11 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Q2_23_promote_green tags were added to gene: MED11.
Mode of inheritance for gene: MED11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MED11 were set to 36001086
Phenotypes for gene: MED11 were set to MED11-associated neurodevelopmental disorder
Review for gene: MED11 was set to GREEN
Added comment: Not associated with a phenotype in OMIM, but is associated with MED11-associated neurodevelopmental disorder in Gen2Phen. PMID: 36001086 reports a single MED11 variant (NM_001001683.4: c.325C>T, p.Arg109*), that segregates with the condition in five unrelated families, however, there is homozygosity between two of these families, idicating that they may be related. Global delay was observed in three individuals from three unrelated familes and seizures were evident in four individuals from four unrelated families. Severe microcephaly was apparent in the two unrelated familes where this parameter was recorded. Overall, the MED11-associated neurodevelopmental disorder appeared to result in profound effects and proved fatal at birth and 10 days in two of the cases reported.
Sources: Literature
Congenital muscular dystrophy v4.7 EMD Achchuthan Shanmugasundram changed review comment from: EDMD1 is a rare X-linked recessive disease characterised by early childhood joint contractures, progressive weakness in muscles and cardiac involvement and can result in sudden death.

PMID:21697856 reported18 patients and three carriers identified with variants in EMD gene. The patients presented with EDMD and the Age at diagnosis was reported for all, but age of onset was only reported for only a few. The youngest patient was 5 days old but asymptomatic, eldest was 55 years. Of those with age of onset reported, 3 had progressive muscle weakness onset from neonatal to 5 years of age.

PMID:31645980 reported a male patient that began having difficulty moving his limb gridle and cervical vertebrae at the age of 5 years. The condition worsened when he was 13 years, and normal exercise was limited, with serious elbow contracture and mild scapular winging contracture.

PMID:31802929 reported one family with 10 affected males with serious cardiac conduction abnormalities at an early age and a high incidence of sudden cardiac death (SCD) along with mild skeletal muscular atrophy, joint contracture and elevated CK levels. and mild skeletal muscular dystrophy.

PMID:34026875 reported three unrelated patients with EDMD, who had cardiac manifestation in childhood without any skeletal muscle phenotypes.

This gene has been associated with phenotypes in OMIM (MIM #310300), which also describes the disorder as primarily of childhood onset. It has not yet been reported in Gene2Phenotype.; to: EDMD1 is a rare X-linked recessive disease characterised by early childhood joint contractures, progressive weakness in muscles and cardiac involvement and can result in sudden death.

PMID:21697856 reported18 patients and three carriers identified with variants in EMD gene. The patients presented with EDMD and the age at diagnosis was reported for all, but age of onset was only reported for only a few. The youngest patient was 5 days old but asymptomatic, eldest was 55 years. Of those with age of onset reported, 3 had progressive muscle weakness onset from neonatal to 5 years of age.

PMID:31645980 reported a male patient that began having difficulty moving his limb gridle and cervical vertebrae at the age of 5 years. The condition worsened when he was 13 years, and normal exercise was limited, with serious elbow contracture and mild scapular winging contracture.

PMID:31802929 reported one family with 10 affected males with serious cardiac conduction abnormalities at an early age and a high incidence of sudden cardiac death (SCD) along with mild skeletal muscular atrophy, joint contracture and elevated CK levels. and mild skeletal muscular dystrophy.

PMID:34026875 reported three unrelated patients with EDMD, who had cardiac manifestation in childhood without any skeletal muscle phenotypes.

This gene has been associated with phenotypes in OMIM (MIM #310300), which also describes the disorder as primarily of childhood onset. It has not yet been reported in Gene2Phenotype.
Congenital myopathy v4.26 BIN1 Achchuthan Shanmugasundram Tag watchlist_moi tag was added to gene: BIN1.
Congenital myopathy v4.26 BIN1 Achchuthan Shanmugasundram Publications for gene: BIN1 were set to 17676042; 27854204; 25260562
Congenital myopathy v4.25 BIN1 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: Only one case with monoallelic BIN1 variant has been reported with childhood-onset myopathy. As there are not sufficient cases, the MOI should remain as "BIALLELIC, autosomal or pseudoautosomal" for now.

"watchlist_moi" tag has been added to review the MOI when new evidence becomes available.
Congenital myopathy v4.25 BIN1 Achchuthan Shanmugasundram Mode of inheritance for gene: BIN1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Congenital myopathy v4.24 BIN1 Achchuthan Shanmugasundram reviewed gene: BIN1: Rating: ; Mode of pathogenicity: None; Publications: 29103045; Phenotypes: ; Mode of inheritance: None
Congenital myopathy v4.24 TPM2 Achchuthan Shanmugasundram Tag Q2_23_NHS_review tag was added to gene: TPM2.
Congenital myopathy v4.24 TPM2 Achchuthan Shanmugasundram Tag Q2_23_MOI tag was added to gene: TPM2.
Congenital myopathy v4.24 TPM2 Achchuthan Shanmugasundram changed review comment from: Comment on mode of inheritance: Three unrelated cases are reported with biallelic variants in TPM2. This is sufficient evidence to update the MOI from "MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown" to "BOTH monoallelic and biallelic, autosomal or pseudoautosomal" in the next major review.; to: Comment on mode of inheritance: Three unrelated cases are reported with biallelic variants in TPM2. This is sufficient evidence to update the MOI from "MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown" to "BOTH monoallelic and biallelic, autosomal or pseudoautosomal" in the next major review.
Congenital myopathy v4.24 TPM2 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: Three unrelated cases are reported with biallelic variants in TPM2. This is sufficient evidence to update the MOI from "MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown" to "BOTH monoallelic and biallelic, autosomal or pseudoautosomal" in the next major review.
Congenital myopathy v4.24 TPM2 Achchuthan Shanmugasundram Mode of inheritance for gene: TPM2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Congenital myopathy v4.23 TPM2 Achchuthan Shanmugasundram changed review comment from: PMID:19155175 reported the identification of a homozygous null variant in TPM2 gene in a patient presented with nemaline myopathy associated with a non-lethal multiple pterygium syndrome.

Among 28 patients from 27 families reported in PMID:24692096, only one patient presenting with nemaline myopathy and pterygia was identified with recessive TPM2 variant.

A homozygous intronic sequence variant was identified in the patient reported with Escobar variant of multiple pterygium syndrome and congenital myopathy in PMID:33558124.

Only phenotypes associated with monoallelic variants (and NOT biallelic variants) are currently reported in OMIM and in Gene2Phenotype.

; to: PMID:19155175 reported the identification of a homozygous null variant in TPM2 gene in a patient presented with nemaline myopathy associated with a non-lethal multiple pterygium syndrome.

Among 28 patients from 27 families reported in PMID:24692096, only one patient presenting with nemaline myopathy and pterygia was identified with recessive TPM2 variant.

A homozygous intronic sequence variant was identified in the patient reported with Escobar variant of multiple pterygium syndrome and congenital myopathy in PMID:33558124.

Only phenotypes associated with monoallelic variants (and NOT biallelic variants) are currently reported in OMIM and in Gene2Phenotype.
Congenital myopathy v4.23 TPM2 Achchuthan Shanmugasundram changed review comment from: Three unrelated cases were reported with biallelic variants in TPM2.; to: PMID:19155175 reported the identification of a homozygous null variant in TPM2 gene in a patient presented with nemaline myopathy associated with a non-lethal multiple pterygium syndrome.

Among 28 patients from 27 families reported in PMID:24692096, only one patient presenting with nemaline myopathy and pterygia was identified with recessive TPM2 variant.

A homozygous intronic sequence variant was identified in the patient reported with Escobar variant of multiple pterygium syndrome and congenital myopathy in PMID:33558124.

Only phenotypes associated with monoallelic variants (and NOT biallelic variants) are currently reported in OMIM and in Gene2Phenotype.
Congenital myopathy v4.23 TNNT1 Achchuthan Shanmugasundram Tag Q2_23_MOI tag was added to gene: TNNT1.
Tag Q2_23_NHS_review tag was added to gene: TNNT1.
Congenital myopathy v4.23 TNNT1 Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: TNNT1.
Tag Q2_23_NHS_review was removed from gene: TNNT1.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.3 ALPK1 Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: ALPK1.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.3 ALPK1 Arina Puzriakova Classified gene: ALPK1 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.3 ALPK1 Arina Puzriakova Added comment: Comment on list classification: This gene is associated with a phenotype in OMIM and Gene2Phenotype (Strong). There is enough evidence to support a gene-disease association - recurrent infections present in some. This gene should be rated Green at the next review.

PMID: 35868845 - 27 patients with ROSAH syndrome, in vitro assays and systematic analysis demonstrated inflammatory features establishing ROSAH as autoinflammatory disease.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.3 ALPK1 Arina Puzriakova Gene: alpk1 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.2 ALPK1 Arina Puzriakova Phenotypes for gene: ALPK1 were changed from ROSAH syndrome to ROSAH syndrome, OMIM:614979
Congenital myopathy v4.23 TPM2 Achchuthan Shanmugasundram reviewed gene: TPM2: Rating: GREEN; Mode of pathogenicity: None; Publications: 19155175, 24692096, 33558124; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital myopathy v4.23 TNNT1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: TNNT1.
Tag Q2_23_NHS_review tag was added to gene: TNNT1.
Congenital myopathy v4.23 TNNT1 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: As reviewed by Anna Sarkozy, monoallelic variants in TNNT1 have been reported in two unrelated families with nemaline myopathy and supported by in vitro functional studies. There is sufficient evidence available for updating the MOI from "BIALLELIC, autosomal or pseudoautosomal" to "BOTH monoallelic and biallelic, autosomal or pseudoautosomal" in the next GMS review.
Congenital myopathy v4.23 TNNT1 Achchuthan Shanmugasundram Mode of inheritance for gene: TNNT1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Congenital myopathy v4.22 TNNT1 Achchuthan Shanmugasundram reviewed gene: TNNT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29178646, 35510366; Phenotypes: Nemaline myopathy 5, Amish type, OMIM:605355; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital myopathy v4.22 NEB Achchuthan Shanmugasundram Tag watchlist_moi tag was added to gene: NEB.
Congenital myopathy v4.22 NEB Achchuthan Shanmugasundram commented on gene: NEB
Congenital myopathy v4.22 MYH7 Achchuthan Shanmugasundram Tag Q2_23_NHS_review tag was added to gene: MYH7.
Congenital myopathy v4.22 MYH3 Achchuthan Shanmugasundram Tag Q2_23_NHS_review tag was added to gene: MYH3.
Congenital myopathy v4.22 MYH3 Achchuthan Shanmugasundram Tag Q2_23_MOI tag was added to gene: MYH3.
Congenital myopathy v4.22 MYH3 Achchuthan Shanmugasundram Phenotypes for gene: MYH3 were changed from Arthrogryposis, distal, type 2A (Freeman-Sheldon), OMIM:193700; Arthrogryposis, distal, type 2B3 (Sheldon-Hall), OMIM:618436 to Arthrogryposis, distal, type 2A (Freeman-Sheldon), OMIM:193700; Arthrogryposis, distal, type 2B3 (Sheldon-Hall), OMIM:618436; Contractures, pterygia, and spondylocarpostarsal fusion syndrome 1A, OMIM:178110; Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1B, OMIM:618469
Congenital myopathy v4.21 MYH3 Achchuthan Shanmugasundram Publications for gene: MYH3 were set to 18695058; 26578207; 29805041; 32902138
Congenital myopathy v4.21 MYH3 Achchuthan Shanmugasundram Publications for gene: MYH3 were set to 18695058; 26578207
Congenital myopathy v4.20 MYH3 Achchuthan Shanmugasundram Mode of inheritance for gene: MYH3 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Congenital myopathy v4.19 MYH3 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: As reviewed by Anna Sarkozy, there is sufficient evidence for updating the MOI of this gene from "MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown" to "BOTH monoallelic and biallelic, autosomal or pseudoautosomal" in the next major review.
Congenital myopathy v4.19 MYH3 Achchuthan Shanmugasundram Mode of inheritance for gene: MYH3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital myopathy v4.18 MYH3 Achchuthan Shanmugasundram reviewed gene: MYH3: Rating: GREEN; Mode of pathogenicity: None; Publications: 29805041, 32902138; Phenotypes: Arthrogryposis, distal, type 2A (Freeman-Sheldon), OMIM:193700, Arthrogryposis, distal, type 2B3 (Sheldon-Hall), OMIM:618436, Contractures, pterygia, and spondylocarpostarsal fusion syndrome 1A, OMIM:178110, Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1B, OMIM:618469; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital myopathy v4.18 DNM2 Achchuthan Shanmugasundram commented on gene: DNM2: The "watchlist_moi" tag is added to this gene to review the MOI in light of any new evidence as there is one family reported with biallelic inheritance.
Congenital myopathy v4.18 DNM2 Achchuthan Shanmugasundram Tag watchlist_moi tag was added to gene: DNM2.
Congenital myopathy v4.18 DNM2 Achchuthan Shanmugasundram Phenotypes for gene: DNM2 were changed from Centronuclear myopathy 1, OMIM:160150; Lethal congenital contracture syndrome 5, OMIM:615368 to Centronuclear myopathy 1, OMIM:160150; Lethal congenital contracture syndrome 5, OMIM:615368
Congenital myopathy v4.17 DNM2 Achchuthan Shanmugasundram Phenotypes for gene: DNM2 were changed from Centronuclear myopathy 1, OMIM:160150 to Centronuclear myopathy 1, OMIM:160150; Lethal congenital contracture syndrome 5, OMIM:615368
Congenital myopathy v4.16 DNM2 Achchuthan Shanmugasundram Publications for gene: DNM2 were set to 22396310
Congenital myopathy v4.15 DNM2 Achchuthan Shanmugasundram reviewed gene: DNM2: Rating: ; Mode of pathogenicity: None; Publications: 23092955; Phenotypes: Lethal congenital contracture syndrome 5, OMIM:615368; Mode of inheritance: None
Congenital muscular dystrophy v4.7 EMD Achchuthan Shanmugasundram Tag Q2_23_NHS_review tag was added to gene: EMD.
Congenital muscular dystrophy v4.7 EMD Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Anna Sarkozy, patients with Emery-Dreifuss muscular dystrophy 1(EDMD1) present symptoms (skeletal muscle and/ or cardiac manifestations) in childhood./ There is sufficient evidence (>3 cases) for this gene to be promoted to green in the next major review.; to: Comment on list classification: As reviewed by Anna Sarkozy, patients with Emery-Dreifuss muscular dystrophy 1(EDMD1) present symptoms (skeletal muscle and/ or cardiac manifestations) in childhood. There is sufficient evidence (>3 cases) for this gene to be promoted to green in the next major review.
Congenital muscular dystrophy v4.7 DTNA Achchuthan Shanmugasundram Tag Q1_23_NHS_review tag was added to gene: DTNA.
Congenital muscular dystrophy v4.7 BET1 Achchuthan Shanmugasundram Tag Q1_23_NHS_review tag was added to gene: BET1.
Congenital muscular dystrophy v4.7 GOSR2 Achchuthan Shanmugasundram Tag Q1_23_NHS_review tag was added to gene: GOSR2.
Congenital myopathy v4.15 GBE1 Achchuthan Shanmugasundram Tag Q1_23_NHS_review tag was added to gene: GBE1.
Congenital myopathy v4.15 DNAJB4 Achchuthan Shanmugasundram Tag Q1_23_NHS_review tag was added to gene: DNAJB4.
Congenital myopathy v4.15 COL25A1 Achchuthan Shanmugasundram Tag Q1_23_NHS_review tag was added to gene: COL25A1.
Congenital myopathy v4.15 COL13A1 Achchuthan Shanmugasundram Tag Q1_23_NHS_review tag was added to gene: COL13A1.
Congenital myopathy v4.15 ASCC1 Achchuthan Shanmugasundram Tag Q1_23_NHS_review tag was added to gene: ASCC1.
Congenital muscular dystrophy v4.7 DAG1 Achchuthan Shanmugasundram changed review comment from: "watchlist_moi" tag added to review this gene for MOI change when more monoallelic cases are reported in the literature.; to: "watchlist_moi" tag added to review this gene for MOI change with new evidence.
Paediatric or syndromic cardiomyopathy v3.1 TBX20 Matthew Edwards gene: TBX20 was added
gene: TBX20 was added to Paediatric or syndromic cardiomyopathy. Sources: Other
Mode of inheritance for gene: TBX20 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TBX20 were set to PMID: 33585493; PMID: 275101702, PMID: 28798025; PMID: 32600061, PMID: 22080862
Phenotypes for gene: TBX20 were set to Cardiomyopathy, dilated with or without LVNC; Atrial septal defect, congential heart disease
Penetrance for gene: TBX20 were set to unknown
Review for gene: TBX20 was set to GREEN
Added comment: TBX20 encodes transcription factors involved in the regulation of several important aspects of cardiac development and homeostasis and heart function. Pathogenic variants in TBX20 are widely associated with the complex spectrum of congenital heart defects and it has also been reported in association with dilated cardiomyopathies and heart arrhythmia (PMID: 33585493)
Although loss of function (LoF) has not been clearly established as a disease mechanism for TBX20 in dilated cardiomyopathy (DCM) and left ventricular non-compaction (LVNC), several LoF alterations have been reported in individuals with these conditions, segregating with disease in several families (PMID: 275101702, PMID: 28798025). In addition mouse model studies have shown that mutant mice with conditional Tbx20 ablation in adult cardiomyocytes have dilated hearts with a rapid loss of systolic function and slower conduction and severe arrhythmia (PMID: 32600061, PMID: 22080862). A functional study ofa truncating variant identified in a DCM case, revealed that the truncated TBX20 protein had no transcriptional activity in contrast to its wild-type counterpart, which further supports the previous mouse model findings and LoF as a disease mechanism for DCM/LVNC (PMID: 275101702).
Sources: Other
Congenital muscular dystrophy v4.7 DAG1 Achchuthan Shanmugasundram commented on gene: DAG1: "watchlist_moi" tag added to review this gene for MOI change when more monoallelic cases are reported in the literature.
Congenital muscular dystrophy v4.7 DAG1 Achchuthan Shanmugasundram Tag watchlist_moi tag was added to gene: DAG1.
Congenital muscular dystrophy v4.7 DAG1 Achchuthan Shanmugasundram reviewed gene: DAG1: Rating: ; Mode of pathogenicity: None; Publications: 35082294; Phenotypes: ; Mode of inheritance: None
Congenital muscular dystrophy v4.7 EMD Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: EMD.
Congenital muscular dystrophy v4.7 EMD Achchuthan Shanmugasundram changed review comment from: As reviewed by Anna Sarkozy, patients with Emery-Dreifuss muscular dystrophy 1(EDMD1) present symptoms (skeletal muscle and/ or cardiac manifestations) in childhood.

EDMD1 is a rare X-linked recessive disease characterised by early childhood joint contractures, progressive weakness in muscles and cardiac involvement and can result in sudden death.

PMID:21697856 reported18 patients and three carriers identified with variants in EMD gene. The patients presented with EDMD and the Age at diagnosis was reported for all, but age of onset was only reported for only a few. The youngest patient was 5 days old but asymptomatic, eldest was 55 years. Of those with age of onset reported, 3 had progressive muscle weakness onset from neonatal to 5 years of age.

PMID:31645980 reported a male patient that began having difficulty moving his limb gridle and cervical vertebrae at the age of 5 years. The condition worsened when he was 13 years, and normal exercise was limited, with serious elbow contracture and mild scapular winging contracture.

PMID:31802929 reported one family with 10 affected males with serious cardiac conduction abnormalities at an early age and a high incidence of sudden cardiac death (SCD) along with mild skeletal muscular atrophy, joint contracture and elevated CK levels. and mild skeletal muscular dystrophy.

PMID:34026875 reported three unrelated patients with EDMD, who had cardiac manifestation in childhood without any skeletal muscle phenotypes.

This gene has been associated with phenotypes in OMIM (MIM #310300), which also describes the disorder as primarily of childhood onset. It has not yet been reported in Gene2Phenotype.; to: EDMD1 is a rare X-linked recessive disease characterised by early childhood joint contractures, progressive weakness in muscles and cardiac involvement and can result in sudden death.

PMID:21697856 reported18 patients and three carriers identified with variants in EMD gene. The patients presented with EDMD and the Age at diagnosis was reported for all, but age of onset was only reported for only a few. The youngest patient was 5 days old but asymptomatic, eldest was 55 years. Of those with age of onset reported, 3 had progressive muscle weakness onset from neonatal to 5 years of age.

PMID:31645980 reported a male patient that began having difficulty moving his limb gridle and cervical vertebrae at the age of 5 years. The condition worsened when he was 13 years, and normal exercise was limited, with serious elbow contracture and mild scapular winging contracture.

PMID:31802929 reported one family with 10 affected males with serious cardiac conduction abnormalities at an early age and a high incidence of sudden cardiac death (SCD) along with mild skeletal muscular atrophy, joint contracture and elevated CK levels. and mild skeletal muscular dystrophy.

PMID:34026875 reported three unrelated patients with EDMD, who had cardiac manifestation in childhood without any skeletal muscle phenotypes.

This gene has been associated with phenotypes in OMIM (MIM #310300), which also describes the disorder as primarily of childhood onset. It has not yet been reported in Gene2Phenotype.
Congenital muscular dystrophy v4.7 EMD Achchuthan Shanmugasundram Classified gene: EMD as Amber List (moderate evidence)
Congenital muscular dystrophy v4.7 EMD Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Anna Sarkozy, patients with Emery-Dreifuss muscular dystrophy 1(EDMD1) present symptoms (skeletal muscle and/ or cardiac manifestations) in childhood./ There is sufficient evidence (>3 cases) for this gene to be promoted to green in the next major review.
Congenital muscular dystrophy v4.7 EMD Achchuthan Shanmugasundram Gene: emd has been classified as Amber List (Moderate Evidence).
Congenital muscular dystrophy v4.6 EMD Achchuthan Shanmugasundram edited their review of gene: EMD: Changed publications to: 21697856, 31645980, 31802929, 34026875
Congenital muscular dystrophy v4.6 EMD Achchuthan Shanmugasundram Publications for gene: EMD were set to 21697856; 31645980; 31802929; 34026875
Congenital muscular dystrophy v4.6 EMD Achchuthan Shanmugasundram Publications for gene: EMD were set to
Congenital muscular dystrophy v4.5 EMD Achchuthan Shanmugasundram reviewed gene: EMD: Rating: GREEN; Mode of pathogenicity: None; Publications: 21697856, 31645980, 31802929, :34026875; Phenotypes: Emery-Dreifuss muscular dystrophy 1, X-linked, OMIM:310300; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Severe early-onset obesity v4.1 DYRK1B Tracy Lester gene: DYRK1B was added
gene: DYRK1B was added to Severe early-onset obesity. Sources: NHS GMS
Mode of inheritance for gene: DYRK1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DYRK1B were set to 34193236; 34786696; 24827035
Phenotypes for gene: DYRK1B were set to obesity; diabetes
Penetrance for gene: DYRK1B were set to unknown
Review for gene: DYRK1B was set to GREEN
Added comment: This gene is green on the diabetes panel but there are cases in the literature who also have early-onset obesity
34193236: performed whole-exome sequencing in the probands from 2 of 3 multigenerational Iranian families with metabolic syndrome and early-onset coronary artery disease and identified a heterozygous missense mutation in the DYRK1B gene (R102C; 604556.0001) that segregated with disease in all 3 families.
34786696: report a splice variant in a 5yr old with severe ID, autism, obesity and seizures, inherited from affected father and also segregates in 2 affected sisters. RNA studies confimed aberrant splicing leading to LOF
24827035: patients with type 2 diabetes and obesity, identified 2 missense that co-segregated with full penetrance (R252H and K68Q). Age-dependent variable expressivity described with central obesity and insulin resistance apparent in childhood and morbid obesity, severe triglyceridemia and labile type 2 diabetes before age 40. Youngest aged 11.
Sources: NHS GMS
Congenital muscular dystrophy v4.5 DTNA Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: DTNA.
Congenital muscular dystrophy v4.5 DTNA Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Anna Sarkozy (Great Ormond Street Hospital), there is sufficient evidence for this gene to be promoted to GREEN at the next major review.

This gene has not yet been associated with muscular dystrophy phenotype either in OMIM or in G2P.; to: Comment on list classification: As reviewed by Anna Sarkozy (Great Ormond Street Hospital), there is sufficient evidence for this gene to be promoted to GREEN at the next major review.

This gene has not yet been associated with muscular dystrophy phenotype either in OMIM or in Gene2Phenotype.
Congenital muscular dystrophy v4.5 DTNA Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Anna Sarkozy (Great Ormond Street Hospital), there is sufficient evidence for this gene to be promoted to GREEN at the next major review.; to: Comment on list classification: As reviewed by Anna Sarkozy (Great Ormond Street Hospital), there is sufficient evidence for this gene to be promoted to GREEN at the next major review.

This gene has not yet been associated with muscular dystrophy phenotype either in OMIM or in G2P.
Congenital muscular dystrophy v4.5 DTNA Achchuthan Shanmugasundram Classified gene: DTNA as Amber List (moderate evidence)
Congenital muscular dystrophy v4.5 DTNA Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Anna Sarkozy (Great Ormond Street Hospital), there is sufficient evidence for this gene to be promoted to GREEN at the next major review.
Congenital muscular dystrophy v4.5 DTNA Achchuthan Shanmugasundram Gene: dtna has been classified as Amber List (Moderate Evidence).
Congenital muscular dystrophy v4.4 DTNA Achchuthan Shanmugasundram reviewed gene: DTNA: Rating: GREEN; Mode of pathogenicity: None; Publications: 36799992; Phenotypes: muscular dystrophy, MONDO:0020121; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital muscular dystrophy v4.4 DTNA Achchuthan Shanmugasundram Phenotypes for gene: DTNA were changed from muscular dystrophy to muscular dystrophy, MONDO:0020121
Congenital muscular dystrophy v4.3 DTNA Achchuthan Shanmugasundram Publications for gene: DTNA were set to 36799992
Congenital muscular dystrophy v4.3 DTNA Achchuthan Shanmugasundram Publications for gene: DTNA were set to 36799992
Congenital muscular dystrophy v4.2 DTNA Achchuthan Shanmugasundram Publications for gene: DTNA were set to 36799992
Congenital muscular dystrophy v4.2 DTNA Achchuthan Shanmugasundram Publications for gene: DTNA were set to PMID: 36799992
Congenital muscular dystrophy v4.1 GOSR2 Achchuthan Shanmugasundram edited their review of gene: GOSR2: Changed phenotypes to: Muscular dystrophy, congenital, with or without seizures, OMIM:620166
Congenital myopathy v4.15 GBE1 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: GBE1.
Congenital myopathy v4.15 GBE1 Achchuthan Shanmugasundram Classified gene: GBE1 as Amber List (moderate evidence)
Congenital myopathy v4.15 GBE1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Anna Sarkozy (Great Ormond Street Hospital), biallelic variants in GBE1 has been reported in sufficient number of cases presenting with fetal akinesia/hypokinesia, arthrogryposis multiplex congenita and severe congenital myopathies. Hence, this gene can be promoted to GREEN rating at the next major review.

This gene has been associated with phenotypes in both OMIM and Gene2Phenotype (with 'definitive' rating).
Congenital myopathy v4.15 GBE1 Achchuthan Shanmugasundram Gene: gbe1 has been classified as Amber List (Moderate Evidence).
Congenital myopathy v4.14 GBE1 Achchuthan Shanmugasundram reviewed gene: GBE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23218673, 26578207, 30303820, 30569318; Phenotypes: Glycogen storage disease IV, OMIM:232500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital myopathy v4.14 GBE1 Achchuthan Shanmugasundram Publications for gene: GBE1 were set to PMID: 23218673; 30303820; PMID: 26578207
Congenital myopathy v4.13 DNAJB4 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: DNAJB4.
Congenital myopathy v4.13 DNAJB4 Achchuthan Shanmugasundram Publications for gene: DNAJB4 were set to PMID: 36264506
Congenital myopathy v4.12 DNAJB4 Achchuthan Shanmugasundram Classified gene: DNAJB4 as Amber List (moderate evidence)
Congenital myopathy v4.12 DNAJB4 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Anna Sarkozy (Great Ormond Street Hospital), there is sufficient evidence (three unrelated cases and functional evidence from mouse models) for promoting this gene to GREEN at the next major review.

This gene has not yet been associated with phenotypes in OMIM, but has been reported in Gene2Phenotype with 'limited' rating.
Congenital myopathy v4.12 DNAJB4 Achchuthan Shanmugasundram Gene: dnajb4 has been classified as Amber List (Moderate Evidence).
Congenital myopathy v4.11 COL25A1 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: COL25A1.
Congenital myopathy v4.11 COL25A1 Achchuthan Shanmugasundram Phenotypes for gene: COL25A1 were changed from rthrogryposis multiplex congenita with or without ocular congenital cranial dysinnervation disorder to Arthrogryposis multiplex congenita with or without ocular congenital cranial dysinnervation disorder
Congenital myopathy v4.10 COL25A1 Achchuthan Shanmugasundram Publications for gene: COL25A1 were set to PMID: 35077597
Congenital myopathy v4.9 COL25A1 Achchuthan Shanmugasundram Classified gene: COL25A1 as Amber List (moderate evidence)
Congenital myopathy v4.9 COL25A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As per expert review by Anna Sarkozy (Great Ormond Street Hospital), the condition caused by biallelic variants in this gene has overlap in clinical presentations with other forms of myopathies. Hence, this gene should be considered for promotion to green at the next major review.
Congenital myopathy v4.9 COL25A1 Achchuthan Shanmugasundram Gene: col25a1 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v5.3 COL25A1 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: COL25A1.
Arthrogryposis v5.3 COL25A1 Achchuthan Shanmugasundram Classified gene: COL25A1 as Amber List (moderate evidence)
Arthrogryposis v5.3 COL25A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (3 unrelated cases) for promoting this gene to GREEN rating at the next major review.
Arthrogryposis v5.3 COL25A1 Achchuthan Shanmugasundram Gene: col25a1 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v5.2 COL25A1 Achchuthan Shanmugasundram gene: COL25A1 was added
gene: COL25A1 was added to Arthrogryposis. Sources: Literature
Mode of inheritance for gene: COL25A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COL25A1 were set to 35077597
Phenotypes for gene: COL25A1 were set to Arthrogryposis multiplex congenita with or without an ocular congenital cranial dysinnervation disorder
Review for gene: COL25A1 was set to GREEN
Added comment: PMID:35077597 reported five patients from three unrelated families identified with biallelic variants in COL25A1 gene presented with a phenotype characterized by arthrogryposis with or without an ocular congenital cranial dysinnervation disorder. The severity of arthrogryposis varied, ranging from mild distal upper limb involvement to arthrogryposis multiplex congenita.

Although the extraocular muscle phenotype has been reported in OMIM (MIM # 616219) and Gene2Phenotype, arthrogryposis has not yet been included in these records.
Sources: Literature
Congenital fibrosis of the extraocular muscles v1.13 COL25A1 Achchuthan Shanmugasundram changed review comment from: PMID:35077597 reported five patients from three unrelated families identified with biallelic variants in COL25A1 gene. Of these four patients from three families had ocular congenital cranial dysinnervation disorder phenotype.

This gene has been associated with this phenotype in both OMIM and Gene2Phenotype (with 'strong' rating).; to: Comment on gene classification: There is sufficient evidence (five unrelated cases) for promoting this gene to GREEN at the next major review.

PMID:35077597 reported five patients from three unrelated families identified with biallelic variants in COL25A1 gene. Of these four patients from three families had ocular congenital cranial dysinnervation disorder phenotype.

This gene has been associated with this phenotype in both OMIM and Gene2Phenotype (with 'strong' rating).
Congenital fibrosis of the extraocular muscles v1.13 COL25A1 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: COL25A1.
Congenital fibrosis of the extraocular muscles v1.13 COL25A1 Achchuthan Shanmugasundram Publications for gene: COL25A1 were set to 25500261
Congenital fibrosis of the extraocular muscles v1.12 COL25A1 Achchuthan Shanmugasundram reviewed gene: COL25A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35077597; Phenotypes: Fibrosis of extraocular muscles, congenital, 5, OMIM:616219; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.11 KDM5A Tracy Lester reviewed gene: KDM5A: Rating: AMBER; Mode of pathogenicity: None; Publications: 33350388; Phenotypes: ASD, lack of speech; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital myaesthenic syndrome v4.1 COL13A1 Achchuthan Shanmugasundram reviewed gene: COL13A1: Rating: ; Mode of pathogenicity: None; Publications: 31449669; Phenotypes: ; Mode of inheritance: None
Congenital myaesthenic syndrome v4.1 COL13A1 Achchuthan Shanmugasundram Tag treatable tag was added to gene: COL13A1.
Congenital myopathy v4.8 COL13A1 Achchuthan Shanmugasundram Classified gene: COL13A1 as Amber List (moderate evidence)
Congenital myopathy v4.8 COL13A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (>3 unrelated cases) for the association of this gene with myopathy and hence it can be promoted to GREEN rating in the next major review.
Congenital myopathy v4.8 COL13A1 Achchuthan Shanmugasundram Gene: col13a1 has been classified as Amber List (Moderate Evidence).
Congenital myopathy v4.7 COL13A1 Achchuthan Shanmugasundram commented on gene: COL13A1: The 'treatable' tag has been added as salbutamol alone or in combination with 3,4-DAP was reported effective in all tested patients (PMID:31449669).
Congenital myopathy v4.7 COL13A1 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: COL13A1.
Congenital myopathy v4.7 COL13A1 Achchuthan Shanmugasundram Tag treatable tag was added to gene: COL13A1.
Congenital myopathy v4.7 COL13A1 Achchuthan Shanmugasundram Phenotypes for gene: COL13A1 were changed from to Myasthenic syndrome, congenital, 19, OMIM:616720
Congenital myopathy v4.6 COL13A1 Achchuthan Shanmugasundram Publications for gene: COL13A1 were set to PMID: 30767057; 31081514
Congenital myopathy v4.5 COL13A1 Achchuthan Shanmugasundram reviewed gene: COL13A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30767057, 31018245, 31449669; Phenotypes: Myasthenic syndrome, congenital, 19, OMIM:616720; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital myopathy v4.5 ASCC1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient evidence (>3 unrelated cases and functional evidence from zebrafish model) for this gene to be promoted to GREEN rating at the next major review.

This gene has already been associated with relevant phenotypes in both OMIM and Gene2Phenotype.; to: Comment on list classification: There is sufficient evidence (>3 unrelated cases and functional evidence from zebrafish model) for this gene to be promoted to GREEN rating at the next major review.

This gene has already been associated with relevant phenotypes in both OMIM and Gene2Phenotype.
Congenital myopathy v4.5 ASCC1 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: ASCC1.
Congenital myopathy v4.5 ASCC1 Achchuthan Shanmugasundram Classified gene: ASCC1 as Amber List (moderate evidence)
Congenital myopathy v4.5 ASCC1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (>3 unrelated cases and functional evidence from zebrafish model) for this gene to be promoted to GREEN rating at the next major review.

This gene has already been associated with relevant phenotypes in both OMIM and Gene2Phenotype.
Congenital myopathy v4.5 ASCC1 Achchuthan Shanmugasundram Gene: ascc1 has been classified as Amber List (Moderate Evidence).
Congenital myopathy v4.4 ASCC1 Achchuthan Shanmugasundram Phenotypes for gene: ASCC1 were changed from prenatal-onset muscle weakness; congenital onset myopathy; arthrogryposis; congenital bone fractures to Spinal muscular atrophy with congenital bone fractures 2, OMIM:616867
Congenital myopathy v4.3 ASCC1 Achchuthan Shanmugasundram Publications for gene: ASCC1 were set to PMID: 35838082; 30327447; 35690317
Congenital myopathy v4.2 ASCC1 Achchuthan Shanmugasundram reviewed gene: ASCC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26924529, 28218388, 30327447, 35276412, 35690317, 35838082; Phenotypes: Spinal muscular atrophy with congenital bone fractures 2, OMIM:616867; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v4.4 UBAP2L Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Konstantinos Varvagiannis, 7 out of 12 unrelated cases from PMID:35977029 had seizures, while 3 of them had a formal diagnosis of epilepsy. This is sufficient evidence to promote this gene to GREEN at the next major review.

This gene has not yet been associated with relevant phenotypes in OMIM, but it has been reported in Gene2Phenotype with 'moderate rating'.; to: Comment on list classification: As reviewed by Konstantinos Varvagiannis, 7 out of 12 unrelated cases from PMID:35977029 had seizures, while 3 of them had a formal diagnosis of epilepsy. This is sufficient evidence to promote this gene to GREEN at the next major review.

This gene has not yet been associated with relevant phenotypes in OMIM, but it has been reported in Gene2Phenotype with 'moderate' rating.
Early onset or syndromic epilepsy v4.4 UBAP2L Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: UBAP2L.
Early onset or syndromic epilepsy v4.4 UBAP2L Achchuthan Shanmugasundram Classified gene: UBAP2L as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.4 UBAP2L Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Konstantinos Varvagiannis, 7 out of 12 unrelated cases from PMID:35977029 had seizures, while 3 of them had a formal diagnosis of epilepsy. This is sufficient evidence to promote this gene to GREEN at the next major review.

This gene has not yet been associated with relevant phenotypes in OMIM, but it has been reported in Gene2Phenotype with 'moderate rating'.
Early onset or syndromic epilepsy v4.4 UBAP2L Achchuthan Shanmugasundram Gene: ubap2l has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.11 UBAP2L Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Konstantinos Varvagiannis, there are at least 8 unrelated cases that had borderline to severe intellectual disability (ID) as identified with formal intellectual evaluation and supported by functional studies from mouse models. This gene therefore has sufficient evidence for promoting to green at the next major review.

This gene has not yet been associated with phenotypes in OMIM, but has been reported in Gene2Phenotype with a 'moderate rating'.; to: Comment on list classification: As reviewed by Konstantinos Varvagiannis, there are at least 8 unrelated cases that had borderline to severe intellectual disability (ID) as identified with formal intellectual evaluation and the association is supported by functional studies from mouse models. This gene therefore has sufficient evidence for promotion to green at the next major review.

This gene has not yet been associated with phenotypes in OMIM, but has been reported in Gene2Phenotype with a 'moderate rating'.
Intellectual disability v5.11 UBAP2L Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.11 UBAP2L Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.11 UBAP2L Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.11 UBAP2L Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.11 UBAP2L Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.11 UBAP2L Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Konstantinos Varvagiannis, there are at least 8 unrelated cases that had borderline to severe intellectual disability (ID) as identified with formal intellectual evaluation and supported by functional studies from mouse models. This gene therefore has sufficient evidence for promoting to green at the next major review.

This gene has not yet been associated with phenotypes in OMIM, but has been reported in Gene2Phenotype with a 'moderate rating'.; to: Comment on list classification: As reviewed by Konstantinos Varvagiannis, there are at least 8 unrelated cases that had borderline to severe intellectual disability (ID) as identified with formal intellectual evaluation and supported by functional studies from mouse models. This gene therefore has sufficient evidence for promoting to green at the next major review.

This gene has not yet been associated with phenotypes in OMIM, but has been reported in Gene2Phenotype with a 'moderate rating'.
Intellectual disability v5.11 UBAP2L Achchuthan Shanmugasundram Classified gene: UBAP2L as Amber List (moderate evidence)
Intellectual disability v5.11 UBAP2L Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Konstantinos Varvagiannis, there are at least 8 unrelated cases that had borderline to severe intellectual disability (ID) as identified with formal intellectual evaluation and supported by functional studies from mouse models. This gene therefore has sufficient evidence for promoting to green at the next major review.

This gene has not yet been associated with phenotypes in OMIM, but has been reported in Gene2Phenotype with a 'moderate rating'.
Intellectual disability v5.11 UBAP2L Achchuthan Shanmugasundram Gene: ubap2l has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Classified gene: UBAP2L as Amber List (moderate evidence)
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Konstantinos Varvagiannis, there are at least 8 unrelated cases that had borderline to severe intellectual disability (ID) as identified with formal intellectual evaluation and supported by functional studies from mouse models. This gene therefore has sufficient evidence for promoting to green at the next major review.

This gene has not yet been associated with phenotypes in OMIM, but has been reported in Gene2Phenotype with a 'moderate rating'.
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Gene: ubap2l has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Classified gene: UBAP2L as Amber List (moderate evidence)
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Konstantinos Varvagiannis, there are at least 8 unrelated cases that had borderline to severe intellectual disability (ID) as identified with formal intellectual evaluation and supported by functional studies from mouse models. This gene therefore has sufficient evidence for promoting to green at the next major review.

This gene has not yet been associated with phenotypes in OMIM, but has been reported in Gene2Phenotype with a 'moderate rating'.
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Gene: ubap2l has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: UBAP2L.
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Classified gene: UBAP2L as Amber List (moderate evidence)
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Konstantinos Varvagiannis, there are at least 8 unrelated cases that had borderline to severe intellectual disability (ID) as identified with formal intellectual evaluation and supported by functional studies from mouse models. This gene therefore has sufficient evidence for promoting to green at the next major review.

This gene has not yet been associated with phenotypes in OMIM, but has been reported in Gene2Phenotype with a 'moderate rating'.
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Gene: ubap2l has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Classified gene: UBAP2L as Amber List (moderate evidence)
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Konstantinos Varvagiannis, there are at least 8 unrelated cases that had borderline to severe intellectual disability (ID) as identified with formal intellectual evaluation and supported by functional studies from mouse models. This gene therefore has sufficient evidence for promoting to green at the next major review.

This gene has not yet been associated with phenotypes in OMIM, but has been reported in Gene2Phenotype with a 'moderate rating'.
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Gene: ubap2l has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Classified gene: UBAP2L as Amber List (moderate evidence)
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Konstantinos Varvagiannis, there are at least 8 unrelated cases that had borderline to severe intellectual disability (ID) as identified with formal intellectual evaluation and supported by functional studies from mouse models. This gene therefore has sufficient evidence for promoting to green at the next major review.

This gene has not yet been associated with phenotypes in OMIM, but has been reported in Gene2Phenotype with a 'moderate rating'.
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Gene: ubap2l has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.9 CAPRIN1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As indicated by the previous reviewers, there is sufficient evidence (>10 unrelated cases) for this gene to be promoted to GREEN at the next major review.

However, this gene has not yet been associated with relevant phenotypes in OMIM, but it has been reported in Gene2Phenotype with 'moderate' rating.; to: Comment on list classification: As indicated by the previous reviewers, there is sufficient evidence (>10 unrelated cases and supporting functional evidence) for this gene to be promoted to GREEN at the next major review.

However, this gene has not yet been associated with relevant phenotypes in OMIM, but it has been reported in Gene2Phenotype with 'moderate' rating.
Intellectual disability v5.9 CAPRIN1 Achchuthan Shanmugasundram Mode of inheritance for gene: CAPRIN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.9 CAPRIN1 Achchuthan Shanmugasundram Mode of inheritance for gene: CAPRIN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.9 CAPRIN1 Achchuthan Shanmugasundram Mode of inheritance for gene: CAPRIN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.9 CAPRIN1 Achchuthan Shanmugasundram Mode of inheritance for gene: CAPRIN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.9 CAPRIN1 Achchuthan Shanmugasundram Mode of inheritance for gene: CAPRIN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.8 CAPRIN1 Achchuthan Shanmugasundram Publications for gene: CAPRIN1 were set to 23849776; 35979925; 36136249
Intellectual disability v5.8 CAPRIN1 Achchuthan Shanmugasundram Publications for gene: CAPRIN1 were set to 23849776; 35979925; 36136249
Intellectual disability v5.8 CAPRIN1 Achchuthan Shanmugasundram Publications for gene: CAPRIN1 were set to 23849776; 35979925; 36136249
Intellectual disability v5.8 CAPRIN1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.8 CAPRIN1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.8 CAPRIN1 Achchuthan Shanmugasundram Publications for gene: CAPRIN1 were set to 23849776; 35979925; 36136249
Intellectual disability v5.7 CAPRIN1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.7 CAPRIN1 Achchuthan Shanmugasundram Publications for gene: CAPRIN1 were set to 23849776; 35979925; 36136249
Intellectual disability v5.7 CAPRIN1 Achchuthan Shanmugasundram Publications for gene: CAPRIN1 were set to 23849776
Intellectual disability v5.6 CAPRIN1 Achchuthan Shanmugasundram Classified gene: CAPRIN1 as Amber List (moderate evidence)
Intellectual disability v5.6 CAPRIN1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As indicated by the previous reviewers, there is sufficient evidence (>10 unrelated cases) for this gene to be promoted to GREEN at the next major review.

However, this gene has not yet been associated with relevant phenotypes in OMIM, but it has been reported in Gene2Phenotype with 'moderate' rating.
Intellectual disability v5.6 CAPRIN1 Achchuthan Shanmugasundram Gene: caprin1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.6 CAPRIN1 Achchuthan Shanmugasundram Classified gene: CAPRIN1 as Amber List (moderate evidence)
Intellectual disability v5.6 CAPRIN1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As indicated by the previous reviewers, there is sufficient evidence (>10 unrelated cases) for this gene to be promoted to GREEN at the next major review.

However, this gene has not yet been associated with relevant phenotypes in OMIM, but it has been reported in Gene2Phenotype with 'moderate' rating.
Intellectual disability v5.6 CAPRIN1 Achchuthan Shanmugasundram Gene: caprin1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.6 CAPRIN1 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: CAPRIN1.
Intellectual disability v5.6 CAPRIN1 Achchuthan Shanmugasundram Classified gene: CAPRIN1 as Amber List (moderate evidence)
Intellectual disability v5.6 CAPRIN1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As indicated by the previous reviewers, there is sufficient evidence (>10 unrelated cases) for this gene to be promoted to GREEN at the next major review.

However, this gene has not yet been associated with relevant phenotypes in OMIM, but it has been reported in Gene2Phenotype with 'moderate' rating.
Intellectual disability v5.6 CAPRIN1 Achchuthan Shanmugasundram Gene: caprin1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.6 CAPRIN1 Achchuthan Shanmugasundram Classified gene: CAPRIN1 as Amber List (moderate evidence)
Intellectual disability v5.6 CAPRIN1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As indicated by the previous reviewers, there is sufficient evidence (>10 unrelated cases) for this gene to be promoted to GREEN at the next major review.

However, this gene has not yet been associated with relevant phenotypes in OMIM, but it has been reported in Gene2Phenotype with 'moderate' rating.
Intellectual disability v5.6 CAPRIN1 Achchuthan Shanmugasundram Gene: caprin1 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v4.1 CAPRIN1 Achchuthan Shanmugasundram changed review comment from: Comment on classification: This gene should be rated Amber as the two confirmed patients were identified with the same variant, despite additional functional evidence. The 'watchlist' tag has been added to look out for new evidence in order to promote this gene to green.

PMID:36136249 reports two unrelated cases with early-onset ataxia – one with Turkish and another with Italian descent. Both harboured the same heterozygous variant c.1535C>T (p.Pro512Leu). The authors also mention that they were notified by GeneMatcher of a 14 years old female patient with exactly the same de-novo variant and an identical phenotype (cerebellar atrophy, ataxia and motor & sensory axonal neuropathy) as the other two patients.

In silico analyses predict an increased aggregation propensity of the mutated protein. Overexpression of CAPRIN1 protein harbouring P512L variant forms insoluble aggregates and sequester ataxia-related proteins. CAPRIN1 with P512L variant in isogenic iPSC-derived cortical neurons causes reduced neuronal activity and altered stress granule dynamics.

These functional evidences also suggest a gain-of-function mechanism for P512L variant.; to: Comment on classification: This gene should be rated Amber as the two confirmed patients were identified with the same variant, despite additional functional evidence. The 'watchlist' tag has been added to look out for new evidence in order to promote this gene to green.

PMID:36136249 reports two unrelated cases with early-onset ataxia – one with Turkish and another with Italian descent. Both harboured the same heterozygous variant c.1535C>T (p.Pro512Leu). The authors also mention that they were notified by GeneMatcher of a 14 years old female patient with exactly the same de-novo variant and an identical phenotype (cerebellar atrophy, ataxia and motor/ sensory axonal neuropathy) as the other two patients.

In silico analyses predict an increased aggregation propensity of the mutated protein. Overexpression of CAPRIN1 protein harbouring P512L variant forms insoluble aggregates and sequester ataxia-related proteins. CAPRIN1 with P512L variant in isogenic iPSC-derived cortical neurons causes reduced neuronal activity and altered stress granule dynamics.

These functional evidences also suggest a gain-of-function mechanism for P512L variant.
Ataxia and cerebellar anomalies - narrow panel v4.1 CAPRIN1 Achchuthan Shanmugasundram changed review comment from: Comment on classification: This gene should be rated Amber as the two confirmed patients were identified with the same variant, despite additional functional evidence. The 'watchlist' tag has been added to look out for new evidence in order to promote this gene to green.

PMID:36136249 reports two unrelated cases with early-onset ataxia – one with Turkish and another with Italian descent. Both harboured the same heterozygous variant c.1535C>T (p.Pro512Leu). The authors also mention that they were notified by GeneMatcher of a 14 years old female patient with exactly the same de-novo variant and an identical phenotype (cerebellar atrophy, ataxia and motor > sensory axonal neuropathy) as the other two patients.

In silico analyses predict an increased aggregation propensity of the mutated protein. Overexpression of CAPRIN1 protein harbouring P512L variant forms insoluble aggregates and sequester ataxia-related proteins. CAPRIN1 with P512L variant in isogenic iPSC-derived cortical neurons causes reduced neuronal activity and altered stress granule dynamics.

These functional evidences also suggest a gain-of-function mechanism for P512L variant.; to: Comment on classification: This gene should be rated Amber as the two confirmed patients were identified with the same variant, despite additional functional evidence. The 'watchlist' tag has been added to look out for new evidence in order to promote this gene to green.

PMID:36136249 reports two unrelated cases with early-onset ataxia – one with Turkish and another with Italian descent. Both harboured the same heterozygous variant c.1535C>T (p.Pro512Leu). The authors also mention that they were notified by GeneMatcher of a 14 years old female patient with exactly the same de-novo variant and an identical phenotype (cerebellar atrophy, ataxia and motor & sensory axonal neuropathy) as the other two patients.

In silico analyses predict an increased aggregation propensity of the mutated protein. Overexpression of CAPRIN1 protein harbouring P512L variant forms insoluble aggregates and sequester ataxia-related proteins. CAPRIN1 with P512L variant in isogenic iPSC-derived cortical neurons causes reduced neuronal activity and altered stress granule dynamics.

These functional evidences also suggest a gain-of-function mechanism for P512L variant.
Childhood onset hereditary spastic paraplegia v4.2 WASHC5 Achchuthan Shanmugasundram Publications for gene: WASHC5 were set to 17160902
Childhood onset hereditary spastic paraplegia v4.1 WASHC5 Achchuthan Shanmugasundram Tag Q1_23_expert_review tag was added to gene: WASHC5.
Childhood onset hereditary spastic paraplegia v4.1 WASHC5 Achchuthan Shanmugasundram Tag Q1_23_demote_red tag was added to gene: WASHC5.
Childhood onset hereditary spastic paraplegia v4.1 WASHC5 Achchuthan Shanmugasundram reviewed gene: WASHC5: Rating: RED; Mode of pathogenicity: None; Publications: 17160902, 23455931, 26572744, 31814071, 33662919; Phenotypes: Spastic paraplegia 8, autosomal dominant, OMIM:603563; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v3.2 TDP1 Ian Berry reviewed gene: TDP1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 12244316, PMID: 31182267; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Hereditary ataxia with onset in adulthood v4.1 TDP1 Ian Berry reviewed gene: TDP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: PMID: 12244316, PMID: 31182267; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Multiple monogenic benign skin tumours v2.2 PRDM10 Achchuthan Shanmugasundram gene: PRDM10 was added
gene: PRDM10 was added to Multiple monogenic benign skin tumours. Sources: Literature
Mode of inheritance for gene: PRDM10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PRDM10 were set to 36440963
Phenotypes for gene: PRDM10 were set to Fibrofolliculoma, HP:0030436; lipomatosis, MONDO:0006574; renal cell carcinoma, MONDO:0005086
Review for gene: PRDM10 was set to RED
Added comment: Comment on gene rating: This gene should be rated RED as it has only been identified with a variant in this gene from one family.

PMID:36440963 reported a family presenting with skin and mucosal lesions, extensive lipomatosis and renal cell carcinomas. The proband was initially diagnosed with Birt-Hogg-Dubé syndrome (BHD, MIM #135150) based on the presence of fibrofolliculomas, but no pathogenic germline variant was detected in FLCN, the gene associated with BHD. A heterozygous missense variant (p.Cys677Tyr) was identified, which co-segregated with the phenotype in the family.

Functional studies show that Cys677Tyr loses affinity for a regulatory binding motif in the FLCN promoter, abrogating cellular FLCN mRNA and protein levels. Overexpressing inducible PRDM10Cys677Tyr in renal epithelial cells altered the transcription of multiple genes, showing overlap but also differences with the effects of knocking out FLCN.

This gene has not yet been associated with phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Inherited renal cancer v1.24 PRDM10 Achchuthan Shanmugasundram gene: PRDM10 was added
gene: PRDM10 was added to Inherited renal cancer. Sources: Literature
Mode of inheritance for gene: PRDM10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PRDM10 were set to 36440963
Phenotypes for gene: PRDM10 were set to Fibrofolliculoma, HP:0030436; lipomatosis, MONDO:0006574; renal cell carcinoma, MONDO:0005086
Review for gene: PRDM10 was set to RED
Added comment: Comment on gene rating: This gene should be rated RED as it has only been identified with a variant in this gene from one family.

PMID:36440963 reported a family presenting with skin and mucosal lesions, extensive lipomatosis and renal cell carcinomas. The proband was initially diagnosed with Birt-Hogg-Dubé syndrome (BHD, MIM #135150) based on the presence of fibrofolliculomas, but no pathogenic germline variant was detected in FLCN, the gene associated with BHD. A heterozygous missense variant (p.Cys677Tyr) was identified, which co-segregated with the phenotype in the family.

Functional studies show that Cys677Tyr loses affinity for a regulatory binding motif in the FLCN promoter, abrogating cellular FLCN mRNA and protein levels. Overexpressing inducible PRDM10Cys677Tyr in renal epithelial cells altered the transcription of multiple genes, showing overlap but also differences with the effects of knocking out FLCN.

This gene has not yet been associated with phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Congenital myopathy v4.2 DNAJB4 Anna Sarkozy gene: DNAJB4 was added
gene: DNAJB4 was added to Congenital myopathy. Sources: Literature
Mode of inheritance for gene: DNAJB4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAJB4 were set to PMID: 36264506
Phenotypes for gene: DNAJB4 were set to congenital myopathy with early respiratory failure
Penetrance for gene: DNAJB4 were set to unknown
Mode of pathogenicity for gene: DNAJB4 was set to Other
Review for gene: DNAJB4 was set to GREEN
Added comment: biallelic variants in DNAJB4 gene have now been described in three unrelated families, in particular stop gain and missense variants. the phenotype is characterised by axial rigidity and early respiratory failure between the 1st and 4th decade of life. muscle pathology is myopathic with protein inclusions and occasional rimmed vacuoles.
Sources: Literature
Congenital muscular dystrophy v4.1 GOSR2 Anna Sarkozy reviewed gene: GOSR2: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 33639315, 33639315; Phenotypes: congenital muscular dystrophy with secondary alpha-dystroglycanopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital muscular dystrophy v4.1 EMD Anna Sarkozy reviewed gene: EMD: Rating: GREEN; Mode of pathogenicity: Other; Publications: ; Phenotypes: Emery Dreifuss muscular dystrophy, X linked; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Congenital muscular dystrophy v4.1 BET1 Anna Sarkozy reviewed gene: BET1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 34779586; Phenotypes: congenital muscular dystrophy with epilepsy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital muscular dystrophy v4.1 PYROXD1 Anna Sarkozy gene: PYROXD1 was added
gene: PYROXD1 was added to Congenital muscular dystrophy. Sources: Literature
Mode of inheritance for gene: PYROXD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PYROXD1 were set to PMID: 33694278; 30515627
Phenotypes for gene: PYROXD1 were set to muscular dystrophy
Penetrance for gene: PYROXD1 were set to unknown
Mode of pathogenicity for gene: PYROXD1 was set to Other
Review for gene: PYROXD1 was set to GREEN
Added comment: this gene is already included as green gene in the CM panel. there is body of evidence that the clinical spectrum of this gene is wider and also includes dystrophic presentations with raised CK. thus this gene should also be included in the CMD R79 panel
Sources: Literature
Congenital muscular dystrophy v4.1 DAG1 Anna Sarkozy reviewed gene: DAG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35082294; Phenotypes: muscular dystrophy, secondary alpha-dystroglycanopathy, hyper-CKemia; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital myopathy v4.2 TPM2 Anna Sarkozy edited their review of gene: TPM2: Added comment: comment re inheritance: recessive TPM2 pathogenic variant has been described in a patient with multiple pterygium syndrome and congenital myopathy. heterozygous carrier parents were unaffected, supporting recessive inheritance of the variant.; Changed publications to: 33558124; Changed phenotypes to: CAP myopathy 2 609285, Nemaline myopathy 4, autosomal dominant 609285, recessively inherited Escobar variant of multiple pterygium syndrome and congenital myopathy; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital myopathy v4.2 TNNT1 Anna Sarkozy edited their review of gene: TNNT1: Added comment: comment re inheritance: both dominant and recessive TNNT1 gene variants have now been reported in patients with congenital myopathies. Dominant mutations are likely acting via a dominant negative mechanism; Changed publications to: 26296490, 25430424, 35510366, 29178646; Changed phenotypes to: nemaline myopathy, Nemaline Myopathy, Recessive, Nemaline myopathy 5, Amish type, 605355, autpsomal dominant nemaline myopathy; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital myopathy v4.2 NEB Anna Sarkozy edited their review of gene: NEB: Added comment: comment re inheritance: a large in frame deletion in the NEB gene have now been described in a three-generation family and was shown to cause the production of a smaller mutant nebulin protein. Thus, it was suggested that this novel mutant nebulin protein has a dominant-negative effect.; Changed publications to: 12207937, 30679003; Changed phenotypes to: nemaline myopathy, Nemaline Myopathy, Recessive, Nemaline myopathy 2, autosomal recessive, 256030, Dominantly inherited distal nemaline/cap myopathy; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital myopathy v4.2 MYH7 Anna Sarkozy edited their review of gene: MYH7: Added comment: re inheritance mode: recessive variants in MYH7 are now well recognised in patients with congenital myopathies; Changed publications to: 15322983, 31130376, 31130376; Changed phenotypes to: Laing Distal Myopathy 160500, congenital myopathy
Congenital myopathy v4.2 MYH3 Anna Sarkozy edited their review of gene: MYH3: Added comment: Recessive MYH3 variants reported in patients with multiple pterygia and this disease entity is designated as "Contractures, pterygia, and variable skeletal fusions syndrome 1B," in OMIM.; Changed publications to: 18695058, 26578207, 32902138; Changed phenotypes to: Arthrogryposis, distal, type 2A 193700, Arthrogryposis, distal, type 2B 601680, Arthrogryposis, distal, type 8 178110, ontractures, pterygia, and variable skeletal fusions syndrome 1B; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital myopathy v4.2 DNM2 Anna Sarkozy edited their review of gene: DNM2: Added comment: biallelic DNM2 variants were also described in three consanguineous patients with lethal congenital syndrome caractherised by akinesia, joint contractures, hypotonia, skeletal abnormalities, and brain and retinal hemorrhages. muscle biopsy and EMG showed myopathic features. in particular, muscle biopsy of one patient showed small rounded fibers with some centralized nuclei, suggestive of a congenital myopathy whereas biopsy of a 2nd patient showed atrophic fibers without obvious centralization of nuclei.; Changed publications to: 22396310, 23092955; Changed phenotypes to: Myopathy, centronuclear, 160150, Charcot-Marie-Tooth disease, axonal, type 2M, 606482, lethal congenital syndrome; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital myopathy v4.2 BIN1 Anna Sarkozy edited their review of gene: BIN1: Added comment: Adult-onset autosomal dominant centronuclear myopathy, also with myalgia and CK elevation; Changed publications to: PMID: 25260562, 27854204; Changed phenotypes to: Centronuclear Myopathy, Recessive, Myopathy, centronuclear, autosomal recessive, 255200, dominant centronuclear myopathy; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital myopathy v4.2 ASCC1 Anna Sarkozy gene: ASCC1 was added
gene: ASCC1 was added to Congenital myopathy. Sources: Literature
Mode of inheritance for gene: ASCC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ASCC1 were set to PMID: 35838082; 30327447; 35690317
Phenotypes for gene: ASCC1 were set to prenatal-onset muscle weakness; congenital onset myopathy; arthrogryposis; congenital bone fractures
Penetrance for gene: ASCC1 were set to unknown
Mode of pathogenicity for gene: ASCC1 was set to Other
Review for gene: ASCC1 was set to GREEN
Added comment: recessive pathogenic variants in ASCC1 gene have now been described in a number of unrelated individuals presenting with a spectrum of phenotypes ranging from prenatal-onset muscle weakness with arthrogryposis and congenital bone fractures to milder presentations without fractures, in keeping with a diagnosis of congenital myopathy .
Sources: Literature
Congenital myopathy v4.2 COL13A1 Anna Sarkozy gene: COL13A1 was added
gene: COL13A1 was added to Congenital myopathy. Sources: Literature
Mode of inheritance for gene: COL13A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COL13A1 were set to PMID: 30767057; 31081514
Penetrance for gene: COL13A1 were set to unknown
Mode of pathogenicity for gene: COL13A1 was set to Other
Added comment: Affected individuals may present mild non specific myopathic findings on muscle biopsy in addition to clinical features of congenital myasthenic syndrome thus strongly in differential with congenital myopathies.
Sources: Literature
Congenital myopathy v4.2 GBE1 Anna Sarkozy gene: GBE1 was added
gene: GBE1 was added to Congenital myopathy. Sources: Literature,Expert Review
Mode of inheritance for gene: GBE1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GBE1 were set to PMID: 23218673; 30303820; PMID: 26578207
Phenotypes for gene: GBE1 were set to arthrogryposis multiplex congenita; foetal akinesias; fetal akinesia deformation sequence; severe congenital myopathy; multiple pterygium syndrome
Penetrance for gene: GBE1 were set to unknown
Mode of pathogenicity for gene: GBE1 was set to Other
Review for gene: GBE1 was set to GREEN
Added comment: recessive pathogenic variants in GBE1 gene responsible for GSD IV, have now been identified in a relevant number of patients presenting with severe early onset neuromuscular conditions, ranging from fetal akinesia deformation sequence, to arthrogryposis multiplex congenita and severe forms of congenital onset myopathies. given the major clinical overlap with severe forms of congenital myopathies, this gene should be considered in differential and included in the R81 panel and tested in patients with possible congenital myopathy.
Sources: Literature, Expert Review
Congenital muscular dystrophy v4.1 DTNA Anna Sarkozy gene: DTNA was added
gene: DTNA was added to Congenital muscular dystrophy. Sources: Literature
Mode of inheritance for gene: DTNA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DTNA were set to PMID: 36799992
Phenotypes for gene: DTNA were set to muscular dystrophy
Penetrance for gene: DTNA were set to unknown
Mode of pathogenicity for gene: DTNA was set to Other
Review for gene: DTNA was set to GREEN
Added comment: Nascimento et al described four unrelated families (12 individuals in total) with monoallelic DTNA variants affecting the coiled-coil domain of α-dystrobrevin. the phenotype is characterised by myalgia, exercise intolerance with variable ages of onset, proximal lower limb weakness from first decade, raised CK levels and one report of rhabdomyolysis. Autism spectrum disorder and learning disabilities were also reported. Muscle biopsies showed mixed myopathic and dystrophic findings, with reduced α-dystrobrevin immunoreactivity and variably reduced immunoreactivity of other DGC proteins.
Sources: Literature
Congenital myopathy v4.2 COL25A1 Anna Sarkozy gene: COL25A1 was added
gene: COL25A1 was added to Congenital myopathy. Sources: Expert list,Literature,Expert Review,Research
Mode of inheritance for gene: COL25A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COL25A1 were set to PMID: 35077597
Phenotypes for gene: COL25A1 were set to rthrogryposis multiplex congenita with or without ocular congenital cranial dysinnervation disorder
Penetrance for gene: COL25A1 were set to unknown
Mode of pathogenicity for gene: COL25A1 was set to Other
Review for gene: COL25A1 was set to GREEN
Added comment: pathogenic recessive variants (missense and splice site) in the COL25A1 gene have now been described in three unrelated families (5 patients in total) presenting with arthrogryposis multiplex congenita with or without an ocular congenital cranial dysinnervation disorder, normal CK and absence of abnormalities on EMG. Given similarities of presentations with other forms of myopathic contractural phenotypes and no/mild progression over time, this condition should be considered in differential for congenital myopathies, thus we would recommend to add this gene as green gene into the R81 panel.
Sources: Expert list, Literature, Expert Review, Research
Sarcoma cancer susceptibility v1.21 RECQL4 Dmitrijs Rots reviewed gene: RECQL4: Rating: GREEN; Mode of pathogenicity: None; Publications: 31604778; Phenotypes: Osteosarcoma; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Monogenic hearing loss v4.5 STX4 Achchuthan Shanmugasundram Classified gene: STX4 as Amber List (moderate evidence)
Monogenic hearing loss v4.5 STX4 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as it has been implicated in congenital hearing impairment, as identified from one family and supported by functional studies.
Monogenic hearing loss v4.5 STX4 Achchuthan Shanmugasundram Gene: stx4 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v4.5 STX4 Achchuthan Shanmugasundram Classified gene: STX4 as Amber List (moderate evidence)
Monogenic hearing loss v4.5 STX4 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as it has been implicated in congenital hearing impairment, as identified from one family and supported by functional studies.
Monogenic hearing loss v4.5 STX4 Achchuthan Shanmugasundram Gene: stx4 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v4.5 STX4 Achchuthan Shanmugasundram Classified gene: STX4 as Amber List (moderate evidence)
Monogenic hearing loss v4.5 STX4 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as it has been implicated in congenital hearing impairment, as identified from one family and supported by functional studies.
Monogenic hearing loss v4.5 STX4 Achchuthan Shanmugasundram Gene: stx4 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v4.4 STX4 Achchuthan Shanmugasundram gene: STX4 was added
gene: STX4 was added to Monogenic hearing loss. Sources: Literature
Mode of inheritance for gene: STX4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STX4 were set to 36355422
Phenotypes for gene: STX4 were set to Hearing impairment, HP:0000365
Review for gene: STX4 was set to AMBER
Added comment: PMID:36355422 reported a large consanguineous Pakistani family with eight affected individuals showing bilateral severe-to-profound hearing impairment. A homozygous splice region variant was identified in STX4 (c.232 + 6T>C), which causes exon skipping and a frameshift, that segregated with hearing impairment in this family.

In silico analysis showed that murine Stx4a is highly and widespread expressed in the developing and adult inner ear. Knockdown of stx4 in zebrafish showed an abnormal startle response, morphological and developmental defects, and a disrupted mechanotransduction function in neuromast hair cells.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability v5.5 ARF1 Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:36345169 reported a paediatric patient identified with a monoallelic de novo missense variant (c.296 G > A; p.R99H) in the ARF1 gene, associated with developmental delay, hypotonia, intellectual disability and motor stereotypies. This patient did not exhibit periventricular heterotopias previously observed in other patients with ARF1 variants (including p.R99H). Functional analysis shows that the pathogenetic mechanism of the R99H-ARF1 variant involves constitutive activation with resultant Golgi and endosomal alterations.
Intellectual disability v5.5 ARF1 Achchuthan Shanmugasundram Publications for gene: ARF1 were set to 28868155; 34353862; 36345169
Intellectual disability v5.5 ARF1 Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:36345169 reported a paediatric patient identified with a monoallelic de novo missense variant (c.296 G > A; p.R99H) in the ARF1 gene, associated with developmental delay, hypotonia, intellectual disability and motor stereotypies. This patient did not exhibit periventricular heterotopias previously observed in other patients with ARF1 variants (including p.R99H). Functional analysis shows that the pathogenetic mechanism of the R99H-ARF1 variant involves constitutive activation with resultant Golgi and endosomal alterations.
Intellectual disability v5.5 ARF1 Achchuthan Shanmugasundram Publications for gene: ARF1 were set to 28868155; 34353862; 36345169
Intellectual disability v5.4 ARF1 Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:36345169 reported a paediatric patient identified with a monoallelic de novo missense variant (c.296 G > A; p.R99H) in the ARF1 gene, associated with developmental delay, hypotonia, intellectual disability and motor stereotypies. This patient did not exhibit periventricular heterotopias previously observed in other patients with ARF1 variants (including p.R99H). Functional analysis shows that the pathogenetic mechanism of the R99H-ARF1 variant involves constitutive activation with resultant Golgi and endosomal alterations.
Intellectual disability v5.4 ARF1 Achchuthan Shanmugasundram Publications for gene: ARF1 were set to 28868155; 34353862; 36345169
Intellectual disability v5.4 ARF1 Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:36345169 reported a paediatric patient identified with a monoallelic de novo missense variant (c.296 G > A; p.R99H) in the ARF1 gene, associated with developmental delay, hypotonia, intellectual disability and motor stereotypies. This patient did not exhibit periventricular heterotopias previously observed in other patients with ARF1 variants (including p.R99H). Functional analysis shows that the pathogenetic mechanism of the R99H-ARF1 variant involves constitutive activation with resultant Golgi and endosomal alterations.
Intellectual disability v5.4 ARF1 Achchuthan Shanmugasundram Publications for gene: ARF1 were set to 28868155; 34353862
Intellectual disability v5.3 FEM1C Achchuthan Shanmugasundram Publications for gene: FEM1C were set to 36336956
Intellectual disability v5.2 FEM1C Achchuthan Shanmugasundram edited their review of gene: FEM1C: Changed publications to: 28135719, 36336956
Intellectual disability v5.2 FEM1C Achchuthan Shanmugasundram gene: FEM1C was added
gene: FEM1C was added to Intellectual disability - microarray and sequencing. 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 Intellectual disability, MONDO:0001071
Review for gene: FEM1C was set to RED
Added comment: 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
Congenital myopathy v4.2 KLHL40 Achchuthan Shanmugasundram Publications for gene: KLHL40 were set to 23746549
Monogenic hearing loss v4.3 ATP11A Achchuthan Shanmugasundram Classified gene: ATP11A as Amber List (moderate evidence)
Monogenic hearing loss v4.3 ATP11A Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated GREEN as it has been implicated in sensorineural hearing loss from four unrelated families, and supported by functional studies from mouse model.
Monogenic hearing loss v4.3 ATP11A Achchuthan Shanmugasundram Gene: atp11a has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v4.2 ATP11A Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: ATP11A.
Monogenic hearing loss v4.2 ATP11A Achchuthan Shanmugasundram gene: ATP11A was added
gene: ATP11A was added to Monogenic hearing loss. Sources: Literature
Mode of inheritance for gene: ATP11A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP11A were set to 35278131; 36300302
Phenotypes for gene: ATP11A were set to Deafness, autosomal dominant 84, OMIM:619810
Review for gene: ATP11A was set to GREEN
Added comment: A heterozygous cryptic donor splice site variant in ATP11A has been identified in a large 6-generation family from Newfoundland in which 16 individuals had progressive sensorineural hearing loss. In addition, several individuals with postlingual-onset progressive hearing loss from two unrelated multigenerational Jewish Israeli families with their origins in Uzbekistan and Afghanistan were also identified with a novel duplication in ATP11A (PMID:35278131).

5500 bp deletion involving the last coding exon of both ATP11A isoforms were identified in the large German multi-generational family that was first reported in PMID:28601886 with auditory synaptopathy/neuropathy, which is a distinct type of sensorineural hearing loss. The deletion is present in all affected individuals from the family and absent in two unaffected family members tested (PMID:36300302).

Functional studies in mice showed ATP11A protein is expressed in mouse inner ear and conditional Atp11a knockout mice showed age-progressive dysfunction or loss of spiral ganglion neurons, recapitulating the human phenotype of auditory neuropathy (PMID:36300302).

This gene has been associated with relevant phenotypes in OMIM, but not in Gene2Phenotype.
Sources: Literature
Long QT syndrome v3.3 KCNH2 Achchuthan Shanmugasundram Publications for gene: KCNH2 were set to 19716085; 31358886; 26888179; 7889573; 9927399
Hereditary ataxia v1.314 NFASC Edoardo Monfrini gene: NFASC was added
gene: NFASC was added to Hereditary ataxia. Sources: Literature
Mode of inheritance for gene: NFASC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NFASC were set to PMID: 30850329, 31608123, 31501903
Phenotypes for gene: NFASC were set to Cerebellar ataxia, Demyelinating neuropathy
Penetrance for gene: NFASC were set to Complete
Review for gene: NFASC was set to GREEN
gene: NFASC was marked as current diagnostic
Added comment: Sources: Literature
Early onset dystonia v1.130 VPS11 Edoardo Monfrini gene: VPS11 was added
gene: VPS11 was added to Early onset dystonia. Sources: Literature
Mode of inheritance for gene: VPS11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS11 were set to PMID: 33452836; 27120463; 27473128; 33871597
Phenotypes for gene: VPS11 were set to Neurodevelopmental disorder; Hypomyelination; Microcephaly; Infantile-onset dystonia; Adult-onset dystonia; Spasticity
Penetrance for gene: VPS11 were set to Complete
Review for gene: VPS11 was set to GREEN
gene: VPS11 was marked as current diagnostic
Added comment: Early-onset patients present hypomyelination, developmental delay, spasticity and dystonia.

A single adult-onset generalized dystonic patient without additional neurologic signs has been reported. This genetic association needs additional cases to be definitively confirmed.
Sources: Literature
Early onset or syndromic epilepsy v4.3 SPTAN1 Sarah Leigh Phenotypes for gene: SPTAN1 were changed from Epileptic encephalopathy, early infantile, 5 to Developmental and epileptic encephalopathy 5, OMIM:613477; developmental and epileptic encephalopathy, 5, MONDO:0013277
Early onset or syndromic epilepsy v4.2 SPTAN1 Sarah Leigh Publications for gene: SPTAN1 were set to Saitsu et al (2010) Am J Hum Genet 86: 881_891
Severe microcephaly v4.1 TRAPPC10 Aleš Maver edited their review of gene: TRAPPC10: Added comment: The study on biallelic TRAPPC10 variants in microcephaly has now been published in PMID: 35298461, reporting 8 individuals with a homozygous loss-of function variant in one family and two affected individuals from the second, unrelated family.; Changed publications to: PMID: 30167849, PMID: 35298461; Changed phenotypes to: Microcephaly, short stature, developmental delay
Corneal dystrophy v3.3 Eleanor Williams Panel version 3.2 has been signed off on 2023-03-22
Corneal dystrophy v3.2 Eleanor Williams Panel signed off version 3.0 has been removed
Mitochondrial disorder with complex II deficiency v2.3 Eleanor Williams Panel version 2.2 has been signed off on 2023-03-22
Mitochondrial disorder with complex II deficiency v2.2 Eleanor Williams Panel signed off version 2.0 has been removed
Ichthyosis and erythrokeratoderma v3.3 Eleanor Williams Panel version 3.2 has been signed off on 2023-03-22
Ichthyosis and erythrokeratoderma v3.2 Eleanor Williams Panel signed off version 3.0 has been removed
Intestinal failure or congenital diarrhoea v3.1 Sarah Leigh Panel version 3.0 has been signed off on 2023-03-22
Intestinal failure or congenital diarrhoea v3.0 Sarah Leigh promoted panel to version 3.0
Cholestasis v3.1 Sarah Leigh Panel version 3.0 has been signed off on 2023-03-22
Cholestasis v3.0 Sarah Leigh promoted panel to version 3.0
Epidermolysis bullosa and congenital skin fragility v2.3 Eleanor Williams Panel version 2.2 has been signed off on 2023-03-22
Epidermolysis bullosa and congenital skin fragility v2.2 Eleanor Williams Panel signed off version 2.0 has been removed
Severe early-onset obesity v4.1 Sarah Leigh Panel version 4.0 has been signed off on 2023-03-22
Severe early-onset obesity v4.0 Sarah Leigh promoted panel to version 4.0
Pituitary hormone deficiency v3.1 Sarah Leigh Panel version 3.0 has been signed off on 2023-03-22
Pituitary hormone deficiency v3.0 Sarah Leigh promoted panel to version 3.0
Childhood onset leukodystrophy v14.3 Eleanor Williams Panel version 14.2 has been signed off on 2023-03-22
Lipodystrophy - childhood onset v4.1 Sarah Leigh Panel version 4.0 has been signed off on 2023-03-22
Lipodystrophy - childhood onset v4.0 Sarah Leigh promoted panel to version 4.0
Other rare neuromuscular disorders v19.2 Eleanor Williams Panel version 19.1 has been signed off on 2023-03-22
Differences in sex development v4.1 Sarah Leigh Panel version 4.0 has been signed off on 2023-03-22
Cystic renal disease v7.2 Arina Puzriakova Panel version 7.1 has been signed off on 2023-03-22
Differences in sex development v4.0 Sarah Leigh promoted panel to version 4.0
Lysosomal storage disorder v3.1 Catherine Snow Panel version 3.0 has been signed off on 2023-03-22
Hereditary ataxia and cerebellar anomalies - childhood onset v12.2 Arina Puzriakova Panel version 12.1 has been signed off on 2023-03-22
Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome v3.1 Sarah Leigh Panel version 3.0 has been signed off on 2023-03-22
Lysosomal storage disorder v3.0 Catherine Snow promoted panel to version 3.0
Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome v3.0 Sarah Leigh promoted panel to version 3.0
Glycogen storage disease v2.1 Catherine Snow Panel version 2.0 has been signed off on 2023-03-22
Glycogen storage disease v2.0 Catherine Snow promoted panel to version 2.0
Rare genetic inflammatory skin disorders v3.1 Sarah Leigh Panel version 3.0 has been signed off on 2023-03-22
Rare genetic inflammatory skin disorders v3.0 Sarah Leigh promoted panel to version 3.0
Cerebral malformation v10.2 Eleanor Williams Panel version 10.1 has been signed off on 2023-03-22
Rare multisystem ciliopathy Super panel v12.3 Arina Puzriakova Panel version 12.2 has been signed off on 2023-03-22
Primary immunodeficiency or monogenic inflammatory bowel disease v4.1 Catherine Snow Panel version 4.0 has been signed off on 2023-03-22
Pigmentary skin disorders v3.1 Sarah Leigh Panel version 3.0 has been signed off on 2023-03-22
Pigmentary skin disorders v3.0 Sarah Leigh promoted panel to version 3.0
Hypotonic infant v25.2 Arina Puzriakova Panel version 25.1 has been signed off on 2023-03-22
Paediatric disorders v35.3 Eleanor Williams Panel version 35.2 has been signed off on 2023-03-22
Palmoplantar keratodermas v3.1 Sarah Leigh Panel version 3.0 has been signed off on 2023-03-22
Palmoplantar keratodermas v3.0 Sarah Leigh promoted panel to version 3.0
Primary immunodeficiency or monogenic inflammatory bowel disease v4.0 Catherine Snow promoted panel to version 4.0
Ichthyosis and erythrokeratoderma v3.1 Sarah Leigh Panel version 3.0 has been signed off on 2022-03-22
Ichthyosis and erythrokeratoderma v3.0 Sarah Leigh promoted panel to version 3.0
Sudden unexplained death or survivors of a cardiac event v19.7 Arina Puzriakova Panel version 19.6 has been signed off on 2023-03-22
Inherited predisposition to acute myeloid leukaemia (AML) v3.1 Catherine Snow Panel version 3.0 has been signed off on 2023-03-22
Inherited predisposition to acute myeloid leukaemia (AML) v3.0 Catherine Snow promoted panel to version 3.0
Epidermolysis bullosa and congenital skin fragility v2.1 Sarah Leigh Panel version 2.0 has been signed off on 2022-03-22
Hereditary Erythrocytosis v2.1 Catherine Snow Panel version 2.0 has been signed off on 2023-03-22
Hereditary Erythrocytosis v2.0 Catherine Snow promoted panel to version 2.0
Epidermolysis bullosa and congenital skin fragility v2.0 Sarah Leigh promoted panel to version 2.0
Unexplained death in infancy and sudden unexplained death in childhood v6.3 Eleanor Williams Panel version 6.2 has been signed off on 2023-03-22
Cytopenia - NOT Fanconi anaemia v3.1 Catherine Snow Panel version 3.0 has been signed off on 2023-03-22
Cytopenia - NOT Fanconi anaemia v3.0 Catherine Snow promoted panel to version 3.0
Bleeding and platelet disorders v3.1 Catherine Snow Panel version 3.0 has been signed off on 2023-03-22
Bleeding and platelet disorders v3.0 Catherine Snow promoted panel to version 3.0
Paediatric pseudo-obstruction syndrome v1.1 Catherine Snow Panel version 1.0 has been signed off on 2023-03-22
Paediatric pseudo-obstruction syndrome v1.0 Catherine Snow promoted panel to version 1.0
Neuronal ceroid lipofuscinosis v2.1 Arina Puzriakova Panel version 2.0 has been signed off on 2023-03-22
Neuronal ceroid lipofuscinosis v2.0 Arina Puzriakova promoted panel to version 2.0
Cardiac arrhythmias v13.5 Eleanor Williams Panel version 13.4 has been signed off on 2023-03-22
Haematological malignancies cancer susceptibility v4.1 Catherine Snow Panel version 4.0 has been signed off on 2023-03-22
Mitochondrial disorder with complex I deficiency v3.1 Arina Puzriakova Panel version 3.0 has been signed off on 2023-03-22
Haematological malignancies cancer susceptibility v4.0 Catherine Snow promoted panel to version 4.0
Mitochondrial disorder with complex I deficiency v3.0 Arina Puzriakova promoted panel to version 3.0
Mitochondrial disorder with complex II deficiency v2.1 Arina Puzriakova Panel version 2.0 has been signed off on 2022-03-22
Breast cancer pertinent cancer susceptibility v2.1 Catherine Snow Panel version 2.0 has been signed off on 2023-03-22
Ectodermal dysplasia v3.1 Sarah Leigh Panel version 3.0 has been signed off on 2023-03-22
Mitochondrial disorder with complex II deficiency v2.0 Arina Puzriakova promoted panel to version 2.0
Breast cancer pertinent cancer susceptibility v2.0 Catherine Snow promoted panel to version 2.0
Ectodermal dysplasia v3.0 Sarah Leigh promoted panel to version 3.0
Cutaneous photosensitivity with a likely genetic cause v3.1 Arina Puzriakova Panel version 3.0 has been signed off on 2023-03-22
Multi locus imprinting disorders v1.3 Achchuthan Shanmugasundram Panel version 1.2 has been signed off on 2023-03-22
Malformations of cortical development v4.1 Eleanor Williams Panel version 4.0 has been signed off on 2023-03-22
Cutaneous photosensitivity with a likely genetic cause v3.0 Arina Puzriakova promoted panel to version 3.0
Malformations of cortical development v4.0 Eleanor Williams promoted panel to version 4.0
Inherited ovarian cancer (without breast cancer) v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2023-03-22
Inherited ovarian cancer (without breast cancer) v4.0 Arina Puzriakova promoted panel to version 4.0
Inherited breast cancer and ovarian cancer v2.1 Arina Puzriakova Panel version 2.0 has been signed off on 2023-03-22
Inherited breast cancer and ovarian cancer v2.0 Arina Puzriakova promoted panel to version 2.0
Li Fraumeni Syndrome v1.1 Achchuthan Shanmugasundram Panel version 1.0 has been signed off on 2023-03-22
Li Fraumeni Syndrome v1.0 Achchuthan Shanmugasundram promoted panel to version 1.0
Fetal anomalies v3.1 Arina Puzriakova Panel version 3.0 has been signed off on 2023-03-22
Severe microcephaly v4.1 Catherine Snow Panel version 4.0 has been signed off on 2023-03-22
Severe microcephaly v4.0 Catherine Snow promoted panel to version 4.0
Fetal anomalies v3.0 Arina Puzriakova promoted panel to version 3.0
Hereditary diffuse gastric cancer v1.1 Catherine Snow Panel version 1.0 has been signed off on 2023-03-22
Hereditary alpha tryptasaemia v1.1 Achchuthan Shanmugasundram Panel version 1.0 has been signed off on 2023-03-22
Hereditary diffuse gastric cancer v1.0 Catherine Snow promoted panel to version 1.0
Hereditary alpha tryptasaemia v1.0 Achchuthan Shanmugasundram promoted panel to version 1.0
Hereditary isolated diabetes insipidus v1.1 Achchuthan Shanmugasundram Panel version 1.0 has been signed off on 2023-03-22
Hereditary isolated diabetes insipidus v1.0 Achchuthan Shanmugasundram promoted panel to version 1.0
Unexplained young onset end-stage renal disease v3.1 Catherine Snow Panel version 3.0 has been signed off on 2023-03-22
Unexplained young onset end-stage renal disease v3.0 Catherine Snow promoted panel to version 3.0
Ovarian cancer pertinent cancer susceptibility v2.1 Arina Puzriakova Panel version 2.0 has been signed off on 2023-03-22
Ovarian cancer pertinent cancer susceptibility v2.0 Arina Puzriakova promoted panel to version 2.0
Inherited prostate cancer v1.1 Achchuthan Shanmugasundram Panel version 1.0 has been signed off on 2023-03-22
Inherited prostate cancer v1.0 Achchuthan Shanmugasundram promoted panel to version 1.0
Membranoproliferative glomerulonephritis including C3 glomerulopathy v3.1 Catherine Snow Panel version 3.0 has been signed off on 2023-03-22
Membranoproliferative glomerulonephritis including C3 glomerulopathy v3.0 Catherine Snow promoted panel to version 3.0
Respiratory ciliopathies including non-CF bronchiectasis v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2023-03-22
Respiratory ciliopathies including non-CF bronchiectasis v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
Corneal dystrophy v3.1 Catherine Snow Panel version 3.0 has been signed off on 2022-03-22
Corneal dystrophy v3.0 Catherine Snow promoted panel to version 3.0
Bilateral congenital or childhood onset cataracts v4.1 Catherine Snow Panel version 4.0 has been signed off on 2023-03-22
Bilateral congenital or childhood onset cataracts v4.0 Catherine Snow promoted panel to version 4.0
Pneumothorax - familial v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2023-03-22
Pneumothorax - familial v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
Adult onset leukodystrophy v3.1 Catherine Snow Panel version 3.0 has been signed off on 2023-03-22
Adult onset leukodystrophy v3.0 Catherine Snow promoted panel to version 3.0
Laterality disorders and isomerism v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2023-03-22
Laterality disorders and isomerism v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
Adult onset neurodegenerative disorder v4.1 Catherine Snow Panel version 4.0 has been signed off on 2023-03-22
Adult onset neurodegenerative disorder v4.0 Catherine Snow promoted panel to version 4.0
Tubulointerstitial kidney disease v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2023-03-22
Tubulointerstitial kidney disease v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
Adult onset hereditary spastic paraplegia v3.1 Catherine Snow Panel version 3.0 has been signed off on 2023-03-22
Renal tubulopathies v4.1 Achchuthan Shanmugasundram Panel version 4.0 has been signed off on 2023-03-22
Adult onset hereditary spastic paraplegia v3.0 Catherine Snow promoted panel to version 3.0
Renal tubulopathies v4.0 Achchuthan Shanmugasundram promoted panel to version 4.0
Hereditary ataxia with onset in adulthood v4.1 Catherine Snow Panel version 4.0 has been signed off on 2023-03-22
Hereditary ataxia with onset in adulthood v4.0 Catherine Snow promoted panel to version 4.0
Childhood onset dystonia, chorea or related movement disorder v3.1 Catherine Snow Panel version 3.0 has been signed off on 2023-03-22
Proteinuric renal disease v4.1 Achchuthan Shanmugasundram Panel version 4.0 has been signed off on 2023-03-22
Childhood onset dystonia, chorea or related movement disorder v3.0 Catherine Snow promoted panel to version 3.0
Proteinuric renal disease v4.0 Achchuthan Shanmugasundram promoted panel to version 4.0
Adult onset dystonia, chorea or related movement disorder v3.1 Catherine Snow Panel version 3.0 has been signed off on 2023-03-22
Adult onset dystonia, chorea or related movement disorder v3.0 Catherine Snow promoted panel to version 3.0
Nephrocalcinosis or nephrolithiasis v4.1 Achchuthan Shanmugasundram Panel version 4.0 has been signed off on 2023-03-22
Nephrocalcinosis or nephrolithiasis v4.0 Achchuthan Shanmugasundram promoted panel to version 4.0
Ehlers Danlos syndrome with a likely monogenic cause v3.1 Catherine Snow Panel version 3.0 has been signed off on 2023-03-22
Ehlers Danlos syndrome with a likely monogenic cause v3.0 Catherine Snow promoted panel to version 3.0
Atypical haemolytic uraemic syndrome v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2023-03-22
Atypical haemolytic uraemic syndrome v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.1 Catherine Snow Panel version 4.0 has been signed off on 2023-03-22
Structural eye disease v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2023-03-22
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.0 Catherine Snow promoted panel to version 4.0
Neurological segmental overgrowth v2.7 Eleanor Williams Panel version 2.6 has been signed off on 2023-03-22
Structural eye disease v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
Familial chylomicronaemia syndrome (FCS) v3.1 Catherine Snow Panel version 3.0 has been signed off on 2023-03-22
DDG2P v3.2 Eleanor Williams Panel version 3.1 has been signed off on 2023-03-22
Familial chylomicronaemia syndrome (FCS) v3.0 Catherine Snow promoted panel to version 3.0
Stickler syndrome v4.1 Achchuthan Shanmugasundram Panel version 4.0 has been signed off on 2023-03-22
Stickler syndrome v4.0 Achchuthan Shanmugasundram promoted panel to version 4.0
Short QT syndrome v3.2 Eleanor Williams Panel version 3.1 has been signed off on 2023-03-22
Rare anaemia v3.1 Catherine Snow Panel version 3.0 has been signed off on 2023-03-22
Rare anaemia v3.0 Catherine Snow promoted panel to version 3.0
Retinal disorders v4.1 Achchuthan Shanmugasundram Panel version 4.0 has been signed off on 2023-03-22
Progressive cardiac conduction disease v2.3 Eleanor Williams Panel version 2.2 has been signed off on 2023-03-22
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2023-03-22
Retinal disorders v4.0 Achchuthan Shanmugasundram promoted panel to version 4.0
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.0 Arina Puzriakova promoted panel to version 4.0
Long QT syndrome v3.2 Eleanor Williams Panel version 3.1 has been signed off on 2023-03-22
Iron metabolism disorders - NOT common HFE mutations v2.1 Catherine Snow Panel version 2.0 has been signed off on 2023-03-22
Iron metabolism disorders - NOT common HFE mutations v2.0 Catherine Snow promoted panel to version 2.0
Optic neuropathy v4.1 Achchuthan Shanmugasundram Panel version 4.0 has been signed off on 2023-03-22
Optic neuropathy v4.0 Achchuthan Shanmugasundram promoted panel to version 4.0
Brugada syndrome and cardiac sodium channel disease v3.3 Eleanor Williams Panel version 3.2 has been signed off on 2023-03-22
Confirmed Fanconi anaemia or Bloom syndrome v2.1 Catherine Snow Panel version 2.0 has been signed off on 2023-03-22
Confirmed Fanconi anaemia or Bloom syndrome v2.0 Catherine Snow promoted panel to version 2.0
Arrhythmogenic right ventricular cardiomyopathy v3.6 Eleanor Williams Panel version 3.5 has been signed off on 2023-03-22
Albinism or congenital nystagmus v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2023-03-22
Clefting v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2023-03-22
Clefting v4.0 Arina Puzriakova promoted panel to version 4.0
Albinism or congenital nystagmus v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
Renal ciliopathies v3.1 Eleanor Williams Panel version 3.0 has been signed off on 2023-03-22
Hypogonadotropic hypogonadism (GMS) v3.1 Catherine Snow Panel version 3.0 has been signed off on 2023-03-22
Skeletal ciliopathies v3.2 Arina Puzriakova Panel version 3.1 has been signed off on 2023-03-22
Renal ciliopathies v3.0 Eleanor Williams promoted panel to version 3.0
Skeletal muscle channelopathy v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2023-03-22
Hypogonadotropic hypogonadism (GMS) v3.0 Catherine Snow promoted panel to version 3.0
Skeletal muscle channelopathy v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
Cystic kidney disease v4.1 Eleanor Williams Panel version 4.0 has been signed off on 2023-03-22
Cystic kidney disease v4.0 Eleanor Williams promoted panel to version 4.0
Skeletal ciliopathies v3.0 Arina Puzriakova promoted panel to version 3.0
Limb disorders v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2023-03-22
Ophthalmological ciliopathies v3.1 Eleanor Williams Panel version 3.0 has been signed off on 2023-03-22
Limb disorders v4.0 Arina Puzriakova promoted panel to version 4.0
Ophthalmological ciliopathies v3.0 Eleanor Williams promoted panel to version 3.0
Mitochondrial disorders v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2023-03-22
Paroxysmal central nervous system disorders v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2023-03-22
Paroxysmal central nervous system disorders v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
White matter disorders and cerebral calcification - narrow panel v3.1 Eleanor Williams Panel version 3.0 has been signed off on 2023-03-22
Mitochondrial disorders v4.0 Arina Puzriakova promoted panel to version 4.0
White matter disorders and cerebral calcification - narrow panel v3.0 Eleanor Williams promoted panel to version 3.0
Cerebral vascular malformations v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2023-03-22
Congenital disorders of glycosylation v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2023-03-22
Congenital disorders of glycosylation v4.0 Arina Puzriakova promoted panel to version 4.0
Cerebral vascular malformations v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
Endocrine neoplasia v3.1 Catherine Snow Panel version 3.0 has been signed off on 2023-03-22
Paediatric disorders - additional genes v3.1 Arina Puzriakova Panel version 3.0 has been signed off on 2023-03-22
Rhabdomyolysis and metabolic muscle disorders v3.1 Eleanor Williams Panel version 3.0 has been signed off on 2023-03-22
Endocrine neoplasia v3.0 Catherine Snow promoted panel to version 3.0
Paediatric disorders - additional genes v3.0 Arina Puzriakova promoted panel to version 3.0
Rhabdomyolysis and metabolic muscle disorders v3.0 Eleanor Williams promoted panel to version 3.0
Catecholaminergic polymorphic VT v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2023-03-22
Neonatal diabetes v4.1 Catherine Snow Panel version 4.0 has been signed off on 2023-03-22
Paediatric motor neuronopathies v3.4 Eleanor Williams Panel version 3.3 has been signed off on 2023-03-22
Catecholaminergic polymorphic VT v4.0 Arina Puzriakova promoted panel to version 4.0
Paediatric motor neuronopathies v3.3 Eleanor Williams Panel signed off version 3.0 has been removed
Cardiac arrhythmias - additional genes v3.1 Arina Puzriakova Panel version 3.0 has been signed off on 2023-03-22
Neonatal diabetes v4.0 Catherine Snow promoted panel to version 4.0
Cardiac arrhythmias - additional genes v3.0 Arina Puzriakova promoted panel to version 3.0
Arthrogryposis v5.1 Achchuthan Shanmugasundram Panel version 5.0 has been signed off on 2023-03-22
Congenital myopathy v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2023-03-22
Arthrogryposis v5.0 Achchuthan Shanmugasundram promoted panel to version 5.0
Congenital hyperinsulinism v3.1 Catherine Snow Panel version 3.0 has been signed off on 2023-03-22
Congenital myopathy v4.0 Arina Puzriakova promoted panel to version 4.0
Congenital hyperinsulinism v3.0 Catherine Snow promoted panel to version 3.0
Paediatric motor neuronopathies v3.1 Eleanor Williams Panel version 3.0 has been signed off on 2023-03-22
Congenital muscular dystrophy v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2023-03-22
Paediatric motor neuronopathies v3.0 Eleanor Williams promoted panel to version 3.0
Congenital muscular dystrophy v4.0 Arina Puzriakova promoted panel to version 4.0
Holoprosencephaly - NOT chromosomal v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2023-03-22
Segmental overgrowth disorders - Deep sequencing v3.4 Catherine Snow Panel version 3.3 has been signed off on 2023-03-22
Holoprosencephaly - NOT chromosomal v4.0 Arina Puzriakova promoted panel to version 4.0
Neurological ciliopathies v3.1 Eleanor Williams Panel version 3.0 has been signed off on 2023-03-22
Likely inborn error of metabolism v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2023-03-22
Osteogenesis imperfecta v4.1 Achchuthan Shanmugasundram Panel version 4.0 has been signed off on 2023-03-22
Neurological ciliopathies v3.0 Eleanor Williams promoted panel to version 3.0
Likely inborn error of metabolism v4.0 Arina Puzriakova promoted panel to version 4.0
Osteogenesis imperfecta v4.0 Achchuthan Shanmugasundram promoted panel to version 4.0
Hypertrophic cardiomyopathy v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2023-03-22
Hypertrophic cardiomyopathy v4.0 Arina Puzriakova promoted panel to version 4.0
Dilated and arrhythmogenic cardiomyopathy v2.9 Arina Puzriakova Panel version 2.8 has been signed off on 2023-03-22
Familial hypercholesterolaemia (GMS) v2.1 Catherine Snow Panel version 2.0 has been signed off on 2023-03-22
Amelogenesis imperfecta v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2023-03-22
Paediatric or syndromic cardiomyopathy v3.1 Arina Puzriakova Panel version 3.0 has been signed off on 2023-03-22
Familial hypercholesterolaemia (GMS) v2.0 Catherine Snow promoted panel to version 2.0
Paediatric or syndromic cardiomyopathy v3.0 Arina Puzriakova promoted panel to version 3.0
Amelogenesis imperfecta v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
Hydrocephalus v4.1 Eleanor Williams Panel version 4.0 has been signed off on 2023-03-22
Ataxia and cerebellar anomalies - narrow panel v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2023-03-22
Hydrocephalus v4.0 Eleanor Williams promoted panel to version 4.0
Ataxia and cerebellar anomalies - narrow panel v4.0 Arina Puzriakova promoted panel to version 4.0
Early onset or syndromic epilepsy v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2023-03-22
Thoracic aortic aneurysm or dissection (GMS) v3.1 Catherine Snow Panel version 3.0 has been signed off on 2023-03-22
Possible mitochondrial disorder - nuclear genes v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2023-03-22
Distal myopathies v3.1 Eleanor Williams Panel version 3.0 has been signed off on 2023-03-22
Thoracic aortic aneurysm or dissection (GMS) v3.0 Catherine Snow promoted panel to version 3.0
Early onset or syndromic epilepsy v4.0 Arina Puzriakova promoted panel to version 4.0
Distal myopathies v3.0 Eleanor Williams promoted panel to version 3.0
Intellectual disability v5.1 Arina Puzriakova Panel version 5.0 has been signed off on 2023-03-22
Possible mitochondrial disorder - nuclear genes v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
Leber hereditary optic neuropathy v2.6 Eleanor Williams Panel version 2.5 has been signed off on 2023-03-22
Childhood solid tumours v4.1 Catherine Snow Panel version 4.0 has been signed off on 2023-03-22
Childhood solid tumours v4.0 Catherine Snow promoted panel to version 4.0
Mitochondrial DNA maintenance disorder v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2023-03-22
Congenital myaesthenic syndrome v4.1 Eleanor Williams Panel version 4.0 has been signed off on 2023-03-22
Mitochondrial DNA maintenance disorder v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
Intellectual disability v5.0 Arina Puzriakova promoted panel to version 5.0
Congenital myaesthenic syndrome v4.0 Eleanor Williams promoted panel to version 4.0
Mitochondrial disorder with complex V deficiency v2.1 Achchuthan Shanmugasundram Panel version 2.0 has been signed off on 2023-03-22
Monogenic hearing loss v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2023-03-22
Thrombophilia with a likely monogenic cause v2.3 Eleanor Williams Panel version 2.2 has been signed off on 2023-03-22
Mitochondrial disorder with complex V deficiency v2.0 Achchuthan Shanmugasundram promoted panel to version 2.0
Monogenic hearing loss v4.0 Arina Puzriakova promoted panel to version 4.0
Childhood onset hereditary spastic paraplegia v4.1 Catherine Snow Panel version 4.0 has been signed off on 2023-03-22
Monogenic hearing loss v3.17 Arina Puzriakova Panel signed off version 3.15 has been removed
Monogenic hearing loss v3.16 Arina Puzriakova Panel version 3.15 has been signed off on 2023-03-22
Childhood onset hereditary spastic paraplegia v4.0 Catherine Snow promoted panel to version 4.0
Hereditary systemic amyloidosis v1.19 Arina Puzriakova Panel version 1.18 has been signed off on 2023-03-22
Skeletal dysplasia v4.1 Eleanor Williams Panel version 4.0 has been signed off on 2023-03-22
Mitochondrial disorder with complex IV deficiency v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2023-03-22
Skeletal dysplasia v4.0 Eleanor Williams promoted panel to version 4.0
Mitochondrial disorder with complex IV deficiency v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
Sporadic aniridia v3.3 Arina Puzriakova Panel version 3.2 has been signed off on 2023-03-22
Mitochondrial liver disease, including transient infantile liver failure v1.10 Arina Puzriakova Panel version 1.9 has been signed off on 2023-03-22
Polycystic liver disease v1.27 Eleanor Williams Panel version 1.26 has been signed off on 2023-03-22
Mitochondrial disorder with complex III deficiency v2.1 Achchuthan Shanmugasundram Panel version 2.0 has been signed off on 2023-03-22
Hereditary neuropathy or pain disorder v3.1 Catherine Snow Panel version 3.0 has been signed off on 2023-03-22
Mitochondrial disorder with complex III deficiency v2.0 Achchuthan Shanmugasundram promoted panel to version 2.0
Hereditary neuropathy or pain disorder v3.0 Catherine Snow promoted panel to version 3.0
Arrhythmogenic right ventricular cardiomyopathy v3.5 Eleanor Williams List of related panels changed from Arrythmogenic cardiomyopathy; R133 to Arrhythmogenic cardiomyopathy; R133
Neonatal diabetes v3.5 Eleanor Williams List of related panels changed from Neonatal diabetes (diagnosed less than 6 months); Neonatal diabetes; Neonatal diabetes diagnosed <6 months; Diabetes - neonatal onset; R143 to Neonatal diabetes (diagnosed less than 6 months); Neonatal diabetes diagnosed <6 months; Diabetes - neonatal onset; R143
Hereditary neuropathy or pain disorder v2.30 Eleanor Williams List of related panels changed from Hereditary neuropathy or pain disorder - NOT PMP22 copy number; Hereditary neuropathy NOT PMP22 copy number; R78 to Hereditary neuropathy NOT PMP22 copy number; R78
Hereditary ataxia with onset in adulthood v3.18 Eleanor Williams List of related panels changed from Hereditary ataxia with onset in adulthood; Hereditary ataxia - adult onset; R54 to Hereditary ataxia - adult onset; R54
Childhood onset dystonia, chorea or related movement disorder v2.13 Eleanor Williams List of related panels changed from Childhood onset dystonia; chorea or related movement disorder; Childhood onset dystonia or chorea or related movement disorder; R57 to Childhood onset dystonia or chorea or related movement disorder; R57
Cerebral malformation v8.25 Eleanor Williams List of related panels changed from Cerebral malformation; Cerebral malformations; R87 to Cerebral malformations; R87
Adult onset hereditary spastic paraplegia v2.26 Arina Puzriakova Panel name changed from Adult onset hereditary spastic paraplegia. to Adult onset hereditary spastic paraplegia
Adult onset hereditary spastic paraplegia v2.25 Eleanor Williams List of related panels changed from Adult onset hereditary spastic paraplegia; Hereditary spastic paraplegia - adult onset; R60 to Hereditary spastic paraplegia - adult onset; R60
Adult onset dystonia, chorea or related movement disorder v2.10 Eleanor Williams List of related panels changed from Adult onset dystonia; chorea or related movement disorder; Adult onset movement disorder; R56 to Adult onset movement disorder; R56
Adult onset leukodystrophy v2.48 Arina Puzriakova List of related panels changed from Adult onset leukodystrophy; White matter disorders - adult onset; R62 to White matter disorders - adult onset; R62
Iron metabolism disorders - NOT common HFE mutations v1.41 Eleanor Williams Panel name changed from Iron metabolism disorders to Iron metabolism disorders - NOT common HFE mutations
List of related panels changed from R96 to Iron metabolism disorders; R96
Other rare neuromuscular disorders v12.270 Arina Puzriakova List of related panels changed from Neuromuscular disorders; Other rare neuromuscular disorders; R381 to Neuromuscular disorders; R381
Polycystic liver disease v1.26 Eleanor Williams Panel name changed from Iron metabolism disorders - NOT common HFE mutations to Polycystic liver disease
List of related panels changed from Polycystic liver disease interim; Polycystic liver disease; R173 to Polycystic liver disease interim; R173
Adult onset neurodegenerative disorder v3.61 Arina Puzriakova List of related panels changed from Adult onset neurodegenerative disorder; Neurodegenerative disorders - adult onset; R58 to Neurodegenerative disorders - adult onset; R58
Holoprosencephaly - NOT chromosomal v3.6 Arina Puzriakova List of related panels changed from Rhombencephalosynapsis; Holoprosencephaly - NOT chromosomal; Holoprosencephaly; R85 to Rhombencephalosynapsis; Holoprosencephaly; R85
Childhood onset hereditary spastic paraplegia v3.28 Arina Puzriakova List of related panels changed from Childhood onset hereditary spastic paraplegia; Hereditary spastic paraplegia - childhood onset; R61 to Hereditary spastic paraplegia - childhood onset; R61
Childhood onset leukodystrophy v10.374 Achchuthan Shanmugasundram List of related panels changed from White matter disorders - childhood onset; Childhood onset leukodystrophy; R109 to White matter disorders - childhood onset; R109
Bilateral congenital or childhood onset cataracts v3.5 Achchuthan Shanmugasundram List of related panels changed from Cataracts; Bilateral congenital or childhood onset cataracts; R31 to Cataracts; R31
Retinal disorders v3.34 SGSH Siying Lin gene: SGSH was added
gene: SGSH was added to Retinal disorders. Sources: Literature
Mode of inheritance for gene: SGSH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SGSH were set to PMID 31718697
Mode of pathogenicity for gene: SGSH was set to Other
Review for gene: SGSH was set to GREEN
Added comment: Reports of late onset retinal dystrophy with mild systemic involvement (attenuated MPS phenotype) associated with biallelic genotypes which include likely hypomorphic alleles. Also two individuals identified in our clinical cohort with retinal dystrophy associated with biallelic SGSH variants.
Sources: Literature
Adult onset leukodystrophy v2.47 Eleanor Williams Panel name changed from White matter disorders - adult onset to Adult onset leukodystrophy
List of related panels changed from R62; Adult onset leukodystrophy to Adult onset leukodystrophy; White matter disorders - adult onset; R62
Childhood onset leukodystrophy v10.373 Achchuthan Shanmugasundram Panel name changed from White matter disorders - childhood onset to Childhood onset leukodystrophy
List of related panels changed from Childhood onset leukodystrophy; R109 to White matter disorders - childhood onset; Childhood onset leukodystrophy; R109
Other rare neuromuscular disorders v12.269 Eleanor Williams Panel name changed from Neuromuscular disorders to Other rare neuromuscular disorders
List of related panels changed from Other rare neuromuscular disorders; R381 to Neuromuscular disorders; Other rare neuromuscular disorders; R381
Sporadic aniridia v3.2 Achchuthan Shanmugasundram Panel name changed from Aniridia to Sporadic aniridia
List of related panels changed from R38 to Aniridia; R38
Adult onset neurodegenerative disorder v3.60 Eleanor Williams Panel name changed from Neurodegenerative disorders - adult onset to Adult onset neurodegenerative disorder
List of related panels changed from R58; Adult onset neurodegenerative disorder to Adult onset neurodegenerative disorder; Neurodegenerative disorders - adult onset; R58
Bilateral congenital or childhood onset cataracts v3.4 Achchuthan Shanmugasundram Panel name changed from Cataracts to Bilateral congenital or childhood onset cataracts
List of related panels changed from R31; Bilateral congenital or childhood onset cataracts to Cataracts; Bilateral congenital or childhood onset cataracts; R31
Likely inborn error of metabolism v3.21 Catherine Snow Panel name changed from Inborn errors of metabolism to Likely inborn error of metabolism - targeted testing not possible
List of related panels changed from Likely inborn error of metabolism - targeted testing not possible; Likely inborn error of metabolism; R98 to Likely inborn error of metabolism - targeted testing not possible; Likely inborn error of metabolism; Inborn errors of metabolism; R98
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v3.14 Eleanor Williams Panel name changed from Limb girdle muscular dystrophy to Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies
List of related panels changed from R82 to Limb girdle muscular dystrophy; R82
Thrombophilia with a likely monogenic cause v2.2 Catherine Snow Panel name changed from Thrombophilia to Thrombophilia with a likely monogenic cause
List of related panels changed from R97 to Thrombophilia; R97
Corneal dystrophy v2.4 Achchuthan Shanmugasundram Panel name changed from Corneal dystrophies to Corneal dystrophy
List of related panels changed from R262 to Corneal dystrophies; R262
Holoprosencephaly - NOT chromosomal v3.5 Eleanor Williams Panel name changed from Holoprosencephaly to Holoprosencephaly - NOT chromosomal
List of related panels changed from Rhombencephalosynapsis; Holoprosencephaly - NOT chromosomal; R85 to Rhombencephalosynapsis; Holoprosencephaly - NOT chromosomal; Holoprosencephaly; R85
Polycystic liver disease v1.25 Catherine Snow Panel name changed from Polycystic liver disease to Iron metabolism disorders - NOT common HFE mutations
List of related panels changed from Polycystic liver disease interim; R173 to Polycystic liver disease interim; Polycystic liver disease; R173
Adult onset hereditary spastic paraplegia v2.24 Eleanor Williams List of related panels changed from R60; Adult onset hereditary spastic paraplegia; Hereditary spastic paraplegia - adult onset to Adult onset hereditary spastic paraplegia; Hereditary spastic paraplegia - adult onset; R60
Polycystic liver disease v1.24 Catherine Snow Panel name changed from Polycystic liver disease interim to Polycystic liver disease
List of related panels changed from R173 to Polycystic liver disease interim; R173
Childhood onset hereditary spastic paraplegia v3.27 Eleanor Williams Panel name changed from Hereditary spastic paraplegia - childhood onset to Childhood onset hereditary spastic paraplegia
List of related panels changed from Childhood onset hereditary spastic paraplegia; R61 to Childhood onset hereditary spastic paraplegia; Hereditary spastic paraplegia - childhood onset; R61
Adult onset hereditary spastic paraplegia v2.23 Eleanor Williams Panel name changed from Hereditary spastic paraplegia - adult onset to Adult onset hereditary spastic paraplegia.
Hereditary neuropathy or pain disorder v2.29 Sarah Leigh Panel name changed from Hereditary neuropathy NOT PMP22 copy number to Hereditary neuropathy or pain disorder - NOT PMP22 copy number
List of related panels changed from R78; Hereditary neuropathy or pain disorder - NOT PMP22 copy number to Hereditary neuropathy or pain disorder - NOT PMP22 copy number; Hereditary neuropathy NOT PMP22 copy number; R78
Adult onset hereditary spastic paraplegia v2.22 Eleanor Williams List of related panels changed from R60; Adult onset hereditary spastic paraplegia to R60; Adult onset hereditary spastic paraplegia; Hereditary spastic paraplegia - adult onset
Multi locus imprinting disorders v1.2 Catherine Snow List of related panels changed from R417 to R417.2
Hereditary ataxia with onset in adulthood v3.17 Sarah Leigh Panel name changed from Hereditary ataxia - adult onset to Hereditary ataxia with onset in adulthood
List of related panels changed from Hereditary ataxia with onset in adulthood; R54 to Hereditary ataxia with onset in adulthood; Hereditary ataxia - adult onset; R54
Early onset or syndromic epilepsy v3.115 Sarah Leigh Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; Component Of Super Panel; GMS signed-off
Early onset or syndromic epilepsy v3.114 Sarah Leigh Panel name changed from Genetic epilepsy syndromes to Early onset or syndromic epilepsy
List of related panels changed from Epilepsy Plus; Epilepsy plus other features; Genetic Epilepsy Syndromes; Epileptic encephalopathy; Familial Focal Epilepsies; Familial Genetic Generalised Epilepsies; Genetic Epilepsies with Febrile Seizures Plus (GEFS+); Genetic Epilepsies with Febrile Seizures Plus; Early onset or syndromic epilepsy; R59 to Epilepsy Plus; Epilepsy plus other features; Genetic Epilepsy Syndromes; Epileptic encephalopathy; Familial Focal Epilepsies; Familial Genetic Generalised Epilepsies; Genetic Epilepsies with Febrile Seizures Plus (GEFS+); Genetic Epilepsies with Febrile Seizures Plus; Early onset or syndromic epilepsy; Genetic epilepsy syndromes; R59
Hypogonadotropic hypogonadism (GMS) v2.6 Catherine Snow Panel name changed from Hypogonadotropic hypogonadism idiopathic to Hypogonadotropic hypogonadism (GMS)
List of related panels changed from R148 to Hypogonadotropic hypogonadism idiopathic; R148
Intellectual disability v4.127 HIST1H4E Eleanor Williams commented on gene: HIST1H4E
Childhood onset dystonia, chorea or related movement disorder v2.12 Sarah Leigh Panel name changed from Childhood onset dystonia or chorea or related movement disorder to Childhood onset dystonia, chorea or related movement disorder
List of related panels changed from R57; Childhood onset dystonia; chorea or related movement disorder to Childhood onset dystonia; chorea or related movement disorder; Childhood onset dystonia or chorea or related movement disorder; R57
Endocrine neoplasia v2.4 Catherine Snow List of related panels changed from R217 to Endocrine neoplasms; R217
Endocrine neoplasia v2.3 Catherine Snow Panel name changed from Endocrine neoplasms to Endocrine neoplasia
Cerebral malformation v8.22 Sarah Leigh Panel name changed from Cerebral malformations to Cerebral malformation
List of related panels changed from Cerebral malformation; R87 to Cerebral malformation; Cerebral malformations; R87
Neonatal diabetes v3.4 Catherine Snow Panel name changed from Diabetes - neonatal onset to Neonatal diabetes
List of related panels changed from Neonatal diabetes (diagnosed less than 6 months); Neonatal diabetes; Neonatal diabetes diagnosed <6 months; R143 to Neonatal diabetes (diagnosed less than 6 months); Neonatal diabetes; Neonatal diabetes diagnosed <6 months; Diabetes - neonatal onset; R143
Adult onset dystonia, chorea or related movement disorder v2.9 Sarah Leigh Panel name changed from Adult onset movement disorder to Adult onset dystonia, chorea or related movement disorder
List of related panels changed from R56; Adult onset dystonia; chorea or related movement disorder to Adult onset dystonia; chorea or related movement disorder; Adult onset movement disorder; R56
Ehlers Danlos syndrome with a likely monogenic cause v2.70 Sarah Leigh Panel name changed from Ehlers Danlos syndromes to Ehlers Danlos syndrome with a likely monogenic cause
List of related panels changed from Classical Ehlers Danlos Syndrome; Classical Ehlers-Danlos Syndrome; Ehlers-Danlos Syndrome (unusual phenotypes e.g. absent pain sense); Ehlers-Danlos syndrome type 3; Kyphoscoliotic Ehlers-Danlos syndrome; EDS; Ehlers-Danlos syndromes; R101 to Classical Ehlers Danlos Syndrome; Classical Ehlers-Danlos Syndrome; Ehlers-Danlos Syndrome (unusual phenotypes e.g. absent pain sense); Ehlers-Danlos syndrome type 3; Kyphoscoliotic Ehlers-Danlos syndrome; EDS; Ehlers-Danlos syndromes; Ehlers Danlos syndromes; R101
Paediatric disorders v24.419 Arina Puzriakova List of related panels changed from Acutely unwell children with a likely monogenic disorder; Congenital malformation and dysmorphism syndromes - microarray and sequencing; Congenital malformation and dysmorphism syndromes; R14; R27 to Congenital malformation and dysmorphism syndromes - microarray and sequencing; Congenital malformation and dysmorphism syndromes; R27
Mitochondrial liver disease, including transient infantile liver failure v1.9 Sarah Leigh Panel name changed from Mitochondrial liver disease to Mitochondrial liver disease, including transient infantile liver failure
List of related panels changed from R317 to Mitochondrial liver disease; R317
Rare syndromic craniosynostosis or isolated multisuture synostosis v3.5 Sarah Leigh Panel name changed from Craniosynostosis to Rare syndromic craniosynostosis or isolated multisuture synostosis
List of related panels changed from Craniosynostosis syndromes; Craniosynostosis syndromes phenotypes; Rare syndromic craniosynostosis or isolated multisuture synostosis; R100 to Craniosynostosis syndromes; Craniosynostosis syndromes phenotypes; Rare syndromic craniosynostosis or isolated multisuture synostosis; Craniosynostosis; R100
Segmental overgrowth disorders - Deep sequencing v3.3 Catherine Snow Panel name changed from Segmental overgrowth disorders to Segmental overgrowth disorders - Deep sequencing
List of related panels changed from Regional overgrowth disorders; R110 to Regional overgrowth disorders; Segmental overgrowth disorders; R110
Li Fraumeni Syndrome v0.9 Achchuthan Shanmugasundram Panel types changed to GMS Rare Disease; GMS signed-off
Familial chylomicronaemia syndrome (FCS) v2.5 Sarah Leigh List of related panels changed from Lipoprotein lipase deficiency;R324 to Lipoprotein lipase deficiency; R324
Leber hereditary optic neuropathy v2.5 Sarah Leigh List of related panels changed from R42.1; R41.3 to R41.3; R42.1
Hereditary alpha tryptasaemia v0.4 Achchuthan Shanmugasundram Panel types changed to GMS Rare Disease; GMS signed-off
Hereditary isolated diabetes insipidus v0.4 Achchuthan Shanmugasundram Panel types changed to GMS Rare Disease; GMS signed-off
Intellectual disability v4.126 Arina Puzriakova Panel name changed from Intellectual disability to Intellectual disability - microarray and sequencing
List of related panels changed from Coarse facial features including Coffin-Siris-like disorders; ID; Moderate; severe or profound intellectual disability; Schizophrenia plus additional features; Intellectual disability - microarray; fragile X and sequencing; R29 to Coarse facial features including Coffin-Siris-like disorders; ID; Moderate; severe or profound intellectual disability; Schizophrenia plus additional features; Intellectual disability - microarray; fragile X and sequencing; Intellectual disability; R29
Inherited prostate cancer v0.5 Achchuthan Shanmugasundram Panel types changed to GMS Rare Disease; GMS signed-off
Leber hereditary optic neuropathy v2.4 Sarah Leigh List of related panels changed from R42.1;R42.1;R41.3 to R42.1; R41.3
Familial hypercholesterolaemia (GMS) v1.13 Arina Puzriakova Panel name changed from Familial hypercholesterolaemia - targeted panel to Familial hypercholesterolaemia (GMS)
List of related panels changed from R134 to Familial hypercholesterolaemia - targeted panel; R134
Paediatric pseudo-obstruction syndrome v0.219 Achchuthan Shanmugasundram Panel types changed to GMS Rare Disease; GMS signed-off
Unexplained death in infancy and sudden unexplained death in childhood v3.195 Achchuthan Shanmugasundram Panel types changed to GMS Rare Disease Virtual; Super Panel; GMS signed-off
Thoracic aortic aneurysm or dissection (GMS) v2.4 Arina Puzriakova Panel name changed from Thoracic aortic aneurysm and dissection to Thoracic aortic aneurysm or dissection (GMS)
List of related panels changed from R125 to Thoracic aortic aneurysm and dissection; R125
Hypertrophic cardiomyopathy v3.5 Arina Puzriakova Panel name changed from Hypertrophic cardiomyopathy - teen and adult to Hypertrophic cardiomyopathy
List of related panels changed from Hypertrophic Cardiomyopathy; HCM; R131 to Hypertrophic cardiomyopathy - teen and adult; HCM; R131
Hereditary diffuse gastric cancer v0.8 Achchuthan Shanmugasundram Panel types changed to GMS Rare Disease; GMS signed-off
Leber hereditary optic neuropathy v2.3 Sarah Leigh List of related panels changed from R42.1 to R42.1;R42.1;R41.3
Dilated and arrhythmogenic cardiomyopathy v2.8 Arina Puzriakova Panel name changed from Dilated cardiomyopathy - adult and teen to Dilated and arrhythmogenic cardiomyopathy
List of related panels changed from R132 to Dilated cardiomyopathy - adult and teen; R132
Paediatric or syndromic cardiomyopathy v2.10 Arina Puzriakova Panel types changed to GMS Rare Disease Virtual; GMS Rare Disease; Component Of Super Panel; GMS signed-off
Paediatric or syndromic cardiomyopathy v2.9 Arina Puzriakova Panel name changed from Cardiomyopathies - including childhood onset to Paediatric or syndromic cardiomyopathy
List of related panels changed from Paediatric or syndromic cardiomyopathy; R135 to Cardiomyopathies - including childhood onset; R135
Familial chylomicronaemia syndrome (FCS) v2.4 Sarah Leigh Panel name changed from Lipoprotein lipase deficiency to Familial chylomicronaemia syndrome (FCS)
List of related panels changed from R324 to Lipoprotein lipase deficiency;R324
Unexplained young onset end-stage renal disease v2.7 Achchuthan Shanmugasundram Panel name changed from Unexplained paediatric onset end-stage renal disease to Unexplained young onset end-stage renal disease
List of related panels changed from R257 to Unexplained paediatric onset end-stage renal disease; R257
Brugada syndrome and cardiac sodium channel disease v3.2 Arina Puzriakova Panel name changed from Brugada syndrome to Brugada syndrome and cardiac sodium channel disease
List of related panels changed from R128 to Brugada syndrome; R128
Arrhythmogenic right ventricular cardiomyopathy v3.4 Arina Puzriakova Panel name changed from Arrhythmogenic cardiomyopathy to Arrhythmogenic right ventricular cardiomyopathy
List of related panels changed from Arrhythmogenic Right Ventricular Cardiomyopathy; Arrythmogenic cardiomyopathy; R133 to Arrythmogenic cardiomyopathy; R133
Membranoproliferative glomerulonephritis including C3 glomerulopathy v2.32 Achchuthan Shanmugasundram Panel name changed from Membranoproliferative glomerulonephritis to Membranoproliferative glomerulonephritis including C3 glomerulopathy
List of related panels changed from PMG; MPGN; Primary Membranoproliferative Glomerulonephritis; Primary membranoproliferative glomerulonephritis; R197 to PMG; MPGN; Primary Membranoproliferative Glomerulonephritis; Primary membranoproliferative glomerulonephritis; Membranoproliferative glomerulonephritis; R197
Childhood solid tumours v3.5 Arina Puzriakova Panel name changed from Tumour predisposition - childhood onset to Childhood solid tumours
List of related panels changed from Paediatric congenital malformation-dysmorphism-tumour syndrome; Paediatric congenital malformation-dysmorphism-tumour syndromes; Paediatric congenital malformation-dysmorphism-tumour sydromes; Paediatric congenital malformation-dysmorphism-tumour syndrome; R359 to Paediatric congenital malformation-dysmorphism-tumour syndrome; Paediatric congenital malformation-dysmorphism-tumour syndromes; Paediatric congenital malformation-dysmorphism-tumour sydromes; Paediatric congenital malformation-dysmorphism-tumour syndrome; Tumour predisposition - childhood onset; R359
Hereditary systemic amyloidosis v1.17 Achchuthan Shanmugasundram Panel name changed from Amyloidosis to Hereditary systemic amyloidosis
List of related panels changed from R204 to Amyloidosis; R204
Monogenic hearing loss v3.15 Arina Puzriakova Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS Rare Disease; Component Of Super Panel; GMS signed-off
Paediatric disorders v24.414 Arina Puzriakova Changed child panels to: Intellectual disability; Inborn errors of metabolism; Monogenic hearing loss; Skeletal dysplasia; Clefting; Limb disorders; DDG2P; Paediatric disorders - additional genes; Renal ciliopathies; Neurological ciliopathies; Ophthalmological ciliopathies; Skeletal ciliopathies
Primary immunodeficiency or monogenic inflammatory bowel disease v3.9 STAT6 Dmitrijs Rots reviewed gene: STAT6: Rating: GREEN; Mode of pathogenicity: None; Publications: 36884218; Phenotypes: Eosinophilia, severe allergy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Adult onset hereditary spastic paraplegia v2.21 RAB3GAP2 Achchuthan Shanmugasundram Classified gene: RAB3GAP2 as Amber List (moderate evidence)
Adult onset hereditary spastic paraplegia v2.21 RAB3GAP2 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene is rated AMBER as all the cases are of childhood-onset.
Adult onset hereditary spastic paraplegia v2.21 RAB3GAP2 Achchuthan Shanmugasundram Gene: rab3gap2 has been classified as Amber List (Moderate Evidence).
Adult onset hereditary spastic paraplegia v2.20 RAB3GAP2 Achchuthan Shanmugasundram Tag Q1_23_promote_green was removed from gene: RAB3GAP2.
Adult onset hereditary spastic paraplegia v2.20 RAB3GAP2 Achchuthan Shanmugasundram Deleted their comment
Childhood onset hereditary spastic paraplegia v3.26 RNF170 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: RNF170.
Childhood onset hereditary spastic paraplegia v3.26 RNF170 Achchuthan Shanmugasundram Classified gene: RNF170 as Amber List (moderate evidence)
Childhood onset hereditary spastic paraplegia v3.26 RNF170 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (6 unrelated cases) for this gene to be promoted to GREEN at the next major review.
Childhood onset hereditary spastic paraplegia v3.26 RNF170 Achchuthan Shanmugasundram Gene: rnf170 has been classified as Amber List (Moderate Evidence).
Childhood onset hereditary spastic paraplegia v3.25 RNF170 Achchuthan Shanmugasundram Phenotypes for gene: RNF170 were changed from Hereditary spastic paraplegia to Spastic paraplegia 85, autosomal recessive, OMIM:619686
Childhood onset hereditary spastic paraplegia v3.24 RNF170 Achchuthan Shanmugasundram Publications for gene: RNF170 were set to 31636353
Childhood onset hereditary spastic paraplegia v3.23 RNF170 Achchuthan Shanmugasundram changed review comment from: PMID:31636353 reported 9 patients from 4 unrelated families with childhood-onset spastic paraplegia. The age of onset of the condition ranged from 2 to 5 years of age and they were all identified with a homozygous variant in RNF170 gene. It is a neurological disorder characterised by the onset of motor symptoms in the first few years of life. Affected individuals have spasticity and hyperreflexia of the lower limbs resulting in gait abnormalities, with oilder patients also having upper limb involvement and axonal polyneuropathy.

PMID:33165979 reported four members from a single family carrying a homozygous stop gain variant in RNF170 and diagnosed with hereditary spastic paraplegia.

PMID:35041108 reported a 7 year old girl with novel homozygous missense variant in RNF170 and she presented with progressive difficulty in walking that started when she was 3 years old, lower limb predominant spastic paraparesis, and mild upper limbs involvement with slight tremor in the hands, all occurring in the absence of neurodevelopmental or growth delays.; to: PMID:31636353 reported 9 patients from 4 unrelated families with childhood-onset spastic paraplegia. The age of onset of the condition ranged from 2 to 5 years of age and they were all identified with a homozygous variant in RNF170 gene. It is a neurological disorder characterised by the onset of motor symptoms in the first few years of life. Affected individuals have spasticity and hyperreflexia of the lower limbs resulting in gait abnormalities, with oilder patients also having upper limb involvement and axonal polyneuropathy.

PMID:33165979 reported four members from a single family carrying a homozygous stop gain variant in RNF170 and diagnosed with hereditary spastic paraplegia.

PMID:35041108 reported a 7 year old girl with novel homozygous missense variant in RNF170 and she presented with progressive difficulty in walking that started when she was 3 years old, lower limb predominant spastic paraparesis, and mild upper limbs involvement with slight tremor in the hands, all occurring in the absence of neurodevelopmental or growth delays.

This gene has been associated with relevant phenotypes in OMIM (MIM #619686), but not yet in Gene2Phenotype.
Childhood onset hereditary spastic paraplegia v3.23 RNF170 Achchuthan Shanmugasundram reviewed gene: RNF170: Rating: GREEN; Mode of pathogenicity: None; Publications: 31636353, 33165979, 35041108; Phenotypes: Spastic paraplegia 85, autosomal recessive, OMIM:619686; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia v3.23 RAB3GAP2 Achchuthan Shanmugasundram Publications for gene: RAB3GAP2 were set to 24482476
Adult onset hereditary spastic paraplegia v2.20 RAB3GAP2 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: RAB3GAP2.
Adult onset hereditary spastic paraplegia v2.20 RAB3GAP2 Achchuthan Shanmugasundram Phenotypes for gene: RAB3GAP2 were changed from Warburg micro syndrome 2, OMIM:614225 to Martsolf syndrome 1, OMIM:212720; Warburg micro syndrome 2, OMIM:614225
Adult onset hereditary spastic paraplegia v2.19 RAB3GAP2 Achchuthan Shanmugasundram Publications for gene: RAB3GAP2 were set to 24482476
Adult onset hereditary spastic paraplegia v2.18 RAB3GAP2 Achchuthan Shanmugasundram Classified gene: RAB3GAP2 as Amber List (moderate evidence)
Adult onset hereditary spastic paraplegia v2.18 RAB3GAP2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (>3 unrelated cases) available for this gene to be considered for a green rating in the next major review.
Adult onset hereditary spastic paraplegia v2.18 RAB3GAP2 Achchuthan Shanmugasundram Gene: rab3gap2 has been classified as Amber List (Moderate Evidence).
Childhood onset hereditary spastic paraplegia v3.22 RAB3GAP2 Achchuthan Shanmugasundram changed review comment from: PMID:32740904 reported 9 cases identified with biallelic variants in RAB3GAP2 gene. Seven of them were diagnosed with Martsolf syndrome 1 (MIM #212720) and the remaining two with Warburg micro syndrome 2 (MIM #614225). All of them presented with spasticity (either paraparesis or quadriparesis) as one of the clinical manifestations. The age of patients ranged from 1 year 4 months to 14 years old, with six ion them under 10 years old.

This gene has been associated with phenotypes in both OMIM and Gene2Phenotype.; to: PMID:32740904 reported 9 cases identified with biallelic variants in RAB3GAP2 gene. Seven of them were diagnosed with Martsolf syndrome 1 (MIM #212720) and the remaining two with Warburg micro syndrome 2 (MIM #614225). All of them presented with spasticity (either paraparesis or quadriparesis) as one of the clinical manifestations. The age of patients ranged from 1 year 4 months to 14 years old, with six of them under 10 years old.

This gene has been associated with phenotypes in both OMIM and Gene2Phenotype.
Adult onset hereditary spastic paraplegia v2.17 RAB3GAP2 Achchuthan Shanmugasundram reviewed gene: RAB3GAP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32740904; Phenotypes: Martsolf syndrome 1, OMIM:212720, Warburg micro syndrome 2, OMIM:614225; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia v3.22 RAB3GAP2 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: RAB3GAP2.
Childhood onset hereditary spastic paraplegia v3.22 RAB3GAP2 Achchuthan Shanmugasundram Classified gene: RAB3GAP2 as Amber List (moderate evidence)
Childhood onset hereditary spastic paraplegia v3.22 RAB3GAP2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (>3 unrelated cases) available for this gene to be considered for a green rating in the next major review.
Childhood onset hereditary spastic paraplegia v3.22 RAB3GAP2 Achchuthan Shanmugasundram Gene: rab3gap2 has been classified as Amber List (Moderate Evidence).
Childhood onset hereditary spastic paraplegia v3.21 RAB3GAP2 Achchuthan Shanmugasundram Phenotypes for gene: RAB3GAP2 were changed from Martsolf syndrome 1, OMIM:212720 to Martsolf syndrome 1, OMIM:212720; Warburg micro syndrome 2, OMIM:614225
Childhood onset hereditary spastic paraplegia v3.20 RAB3GAP2 Achchuthan Shanmugasundram reviewed gene: RAB3GAP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32740904; Phenotypes: Martsolf syndrome 1, OMIM:212720, Warburg micro syndrome 2, OMIM:614225; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v2.17 SMARCC1 Eleanor Williams Added comment: Comment on phenotypes: Adding the OMIM phenotype and removing the gene-checked tag.
Fetal anomalies v2.17 SMARCC1 Eleanor Williams Phenotypes for gene: SMARCC1 were changed from Congenital hydrocephalus; Aqueductal stenosis; Septal agenesis; Corpus callosum abnormalities to Congenital hydrocephalus; Aqueductal stenosis; Septal agenesis; Corpus callosum abnormalities; {Hydrocephalus, congenital, 5, susceptibility to}, OMIM:620241
Fetal anomalies v2.16 SMARCC1 Eleanor Williams Tag gene-checked was removed from gene: SMARCC1.
Hydrocephalus v3.6 SMARCC1 Eleanor Williams Added comment: Comment on phenotypes: Adding the OMIM phenotype and removing the gene-checked tag.
Hydrocephalus v3.6 SMARCC1 Eleanor Williams Phenotypes for gene: SMARCC1 were changed from Congenital hydrocephalus; Aqueductal stenosis; Septal agenesis; Corpus callosum abnormalities to Congenital hydrocephalus; Aqueductal stenosis; Septal agenesis; Corpus callosum abnormalities; {Hydrocephalus, congenital, 5, susceptibility to}, OMIM:620241
Hydrocephalus v3.5 SMARCC1 Eleanor Williams Tag gene-checked was removed from gene: SMARCC1.
Severe microcephaly v3.12 ATP9A Eleanor Williams Phenotypes for gene: ATP9A were changed from Neurodevelopmental delay; Postnatal microcephaly; Failure to thrive; Gastrointestinal symptoms to Neurodevelopmental delay; Postnatal microcephaly; Failure to thrive; Gastrointestinal symptoms; Neurodevelopmental disorder with poor growth and behavioral abnormalities, OMIM:620242
Intellectual disability v4.125 ATP9A Eleanor Williams Tag gene-checked was removed from gene: ATP9A.
Intellectual disability v4.125 ATP9A Eleanor Williams Added comment: Comment on phenotypes: Adding the OMIM phenotype which was added to OMIM in Feb 2023.
Intellectual disability v4.125 ATP9A Eleanor Williams Phenotypes for gene: ATP9A were changed from Global developmental delay; Intellectual disability; Postnatal microcephaly; Failure to thrive; Abnormality of the abdomen to Global developmental delay; Intellectual disability; Postnatal microcephaly; Failure to thrive; Abnormality of the abdomen; Neurodevelopmental disorder with poor growth and behavioral abnormalities, OMIM:620242
Intellectual disability v4.124 TAB2 Achchuthan Shanmugasundram Publications for gene: TAB2 were set to 35971781
Intellectual disability v4.124 TAB2 Achchuthan Shanmugasundram Publications for gene: TAB2 were set to 35971781
Intellectual disability v4.123 TAB2 Achchuthan Shanmugasundram Publications for gene: TAB2 were set to 35971781
Intellectual disability v4.123 TAB2 Achchuthan Shanmugasundram Publications for gene: TAB2 were set to
Intellectual disability v4.122 TAB2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.122 TAB2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.122 TAB2 Achchuthan Shanmugasundram Classified gene: TAB2 as Amber List (moderate evidence)
Intellectual disability v4.122 TAB2 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER. Although there are four unrelated cases reported with ID, ID is part of a broad spectrum of phenotypes and the majority of cases in PMID:35971781 and other previous studies were not reported with ID as part of the phenotype.

ID has not been reported as part of the phenotype either in OMIM or in Gene2Phenotype.
Intellectual disability v4.122 TAB2 Achchuthan Shanmugasundram Gene: tab2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.122 TAB2 Achchuthan Shanmugasundram Classified gene: TAB2 as Amber List (moderate evidence)
Intellectual disability v4.122 TAB2 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER. Although there are four unrelated cases reported with ID, ID is part of a broad spectrum of phenotypes and the majority of cases in PMID:35971781 and other previous studies were not reported with ID as part of the phenotype.

ID has not been reported as part of the phenotype either in OMIM or in Gene2Phenotype.
Intellectual disability v4.122 TAB2 Achchuthan Shanmugasundram Gene: tab2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.121 TAB2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.121 TAB2 Achchuthan Shanmugasundram Classified gene: TAB2 as Amber List (moderate evidence)
Intellectual disability v4.121 TAB2 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER. Although there are four unrelated cases reported with ID, ID is part of a broad spectrum of phenotypes and the majority of cases in PMID:35971781 and other previous studies were not reported with ID as part of the phenotype.

ID has not been reported as part of the phenotype either in OMIM or in Gene2Phenotype.
Intellectual disability v4.121 TAB2 Achchuthan Shanmugasundram Gene: tab2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.121 TAB2 Achchuthan Shanmugasundram Classified gene: TAB2 as Amber List (moderate evidence)
Intellectual disability v4.121 TAB2 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER. Although there are four unrelated cases reported with ID, ID is part of a broad spectrum of phenotypes and the majority of cases in PMID:35971781 and other previous studies were not reported with ID as part of the phenotype.

ID has not been reported as part of the phenotype either in OMIM or in Gene2Phenotype.
Intellectual disability v4.121 TAB2 Achchuthan Shanmugasundram Gene: tab2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.120 TAB2 Achchuthan Shanmugasundram changed review comment from: 4 out of 14 patients identified with heterozygous variants in TAB2 gene in PMID:35971781 were reported with global developmental delay and intellectual disability (ID). Two other patients were reported with motor delay. Although developmental delay was reported in previous studies including the one reviewed by Andrea Haworth below, none of the previous studies reported cases with ID.

Although there are four unrelated cases reported with ID, ID is part of a broad spectrum of phenotypes and a majority of cases in this study and other previous studies did not report ID as part of the phenotype.

ID has not been reported as part of the phenotype either in OMIM or in Gene2Phenotype.; to: 4 out of 14 patients identified with heterozygous variants in TAB2 gene in PMID:35971781 were reported with global developmental delay and intellectual disability (ID). Two other patients were reported with motor delay. Although developmental delay was reported in previous studies including the one reviewed by Andrea Haworth below, none of the previous studies reported cases with ID.
Intellectual disability v4.120 TAB2 Achchuthan Shanmugasundram reviewed gene: TAB2: Rating: AMBER; Mode of pathogenicity: None; Publications: 35971781; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v3.113 SATB2 Sarah Leigh edited their review of gene: SATB2: Added comment: Associated with Glass syndrome, OMIM:612313 and as definitive Gen2Phen gene for the same condition. Table 2 in PMID: 32446642 presents a clincal review of SATB2 variant carriers. Amongst the 35 cases carrying intragenic variants, 14 did not have clinical seizures, 19 had seizures (10 well controlled, 9 somewhat controlled) and the diagnosis was uncertain in two other cases.; Changed rating: GREEN
Early onset or syndromic epilepsy v3.113 SATB2 Sarah Leigh Phenotypes for gene: SATB2 were changed from Glass syndrome, MIM# 612313 to Glass syndrome, OMIM:612313
Intellectual disability v4.120 SUPT16H Achchuthan Shanmugasundram Publications for gene: SUPT16H were set to 31924697; 36226587; 36255738
Intellectual disability v4.120 SUPT16H Achchuthan Shanmugasundram Publications for gene: SUPT16H were set to 31924697; 36226587; 36255738
Intellectual disability v4.119 SUPT16H Achchuthan Shanmugasundram Publications for gene: SUPT16H were set to 31924697; 36226587; 36255738
Intellectual disability v4.120 SUPT16H Achchuthan Shanmugasundram Publications for gene: SUPT16H were set to 31924697; 36226587; 36255738
Intellectual disability v4.119 SUPT16H Achchuthan Shanmugasundram Publications for gene: SUPT16H were set to 31924697; 36226587; 36255738
Intellectual disability v4.119 SUPT16H Achchuthan Shanmugasundram Publications for gene: SUPT16H were set to 31924697; 36226587; 36255738
Intellectual disability v4.119 SUPT16H Achchuthan Shanmugasundram Publications for gene: SUPT16H were set to 31924697; 36226587; 36255738
Intellectual disability v4.119 SUPT16H Achchuthan Shanmugasundram Publications for gene: SUPT16H were set to 31924697; 36226587
Early onset or syndromic epilepsy v3.112 SATB2 Sarah Leigh Tag Q1_23_promote_green tag was added to gene: SATB2.
Early onset or syndromic epilepsy v3.112 SATB2 Sarah Leigh Classified gene: SATB2 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v3.112 SATB2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Early onset or syndromic epilepsy v3.112 SATB2 Sarah Leigh Gene: satb2 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v3.111 KPTN Sarah Leigh Tag watchlist was removed from gene: KPTN.
Tag Q1_23_promote_green tag was added to gene: KPTN.
Early onset or syndromic epilepsy v3.111 KPTN Sarah Leigh edited their review of gene: KPTN: Added comment: Associated with relevant phenotype in OMIM and as strong Gen2Phen gene. At least five KPTN variants have been reported in four unrelated cases of OMIM: 615637, seizures were evident in three unrelated cases (PMID: 24239382;25847626;32358097;32808430).; Changed rating: GREEN
Early onset or syndromic epilepsy v3.111 KPTN Sarah Leigh Classified gene: KPTN as Amber List (moderate evidence)
Early onset or syndromic epilepsy v3.111 KPTN Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Early onset or syndromic epilepsy v3.111 KPTN Sarah Leigh Gene: kptn has been classified as Amber List (Moderate Evidence).
Fetal anomalies v2.16 KPTN Sarah Leigh Phenotypes for gene: KPTN were changed from MACROCEPHALY, NEURODEVELOPMENTAL DELAY, AND SEIZURES to Intellectual developmental disorder, autosomal recessive 41, OMIM:615637; macrocephaly-developmental delay syndrome, MONDO:0014289
Intellectual disability v4.118 KPTN Sarah Leigh Phenotypes for gene: KPTN were changed from MACROCEPHALY, NEURODEVELOPMENTAL DELAY, AND SEIZURES to Intellectual developmental disorder, autosomal recessive 41, OMIM:615637; macrocephaly-developmental delay syndrome, MONDO:0014289
Early onset or syndromic epilepsy v3.110 KPTN Sarah Leigh Phenotypes for gene: KPTN were changed from Mental retardation, autosomal recessive 4,1615637; seizures to Intellectual developmental disorder, autosomal recessive 41, OMIM:615637; macrocephaly-developmental delay syndrome, MONDO:0014289
Early onset or syndromic epilepsy v3.109 KPTN Sarah Leigh Publications for gene: KPTN were set to 24239382; 25847626
Skeletal dysplasia v3.13 EXT2 Sarah Leigh changed review comment from: Biallelic EXT2 variants are also reported in Seizures, scoliosis, and macrocephaly syndrome, OMIM:616682. Table 2 in PMID: 30997052 highlights the phenotypic features of OMIM:616682. Scoliosis, which is relevant to this panel, is seen in 2/4 families reviewed in PMID: 30997052. If scoliosis is observed in more cases of OMIM:616682, then it would be appropriate to change the mode of inheritance of EXT2 to BOTH monoallelic and biallelic. The Watchlist tag has been added to this gene to reflect this situation.; to: Biallelic EXT2 variants are also reported in Seizures, scoliosis, and macrocephaly syndrome, OMIM:616682. Table 2 in PMID: 30997052 highlights the phenotypic features of OMIM:616682. Scoliosis, which is relevant to this panel, is seen in 2/4 families reviewed in PMID: 30997052. If scoliosis is observed in more cases of OMIM:616682, then it would be appropriate to change the mode of inheritance of EXT2 to BOTH monoallelic and biallelic. The Watchlist_moi tag has been added to this gene to reflect this situation.
Skeletal dysplasia v3.13 EXT2 Sarah Leigh Tag watchlist_moi tag was added to gene: EXT2.
Skeletal dysplasia v3.13 EXT2 Sarah Leigh Phenotypes for gene: EXT2 were changed from Exostoses, multiple, type 2 133701 to Exostoses, multiple, type 2, OMIM:133701
Skeletal dysplasia v3.12 EXT2 Sarah Leigh edited their review of gene: EXT2: Added comment: Biallelic EXT2 variants are also reported in Seizures, scoliosis, and macrocephaly syndrome, OMIM:616682. Table 2 in PMID: 30997052 highlights the phenotypic features of OMIM:616682. Scoliosis, which is relevant to this panel, is seen in 2/4 families reviewed in PMID: 30997052. If scoliosis is observed in more cases of OMIM:616682, then it would be appropriate to change the mode of inheritance of EXT2 to BOTH monoallelic and biallelic. The Watchlist tag has been added to this gene to reflect this situation.; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v3.12 EXT2 Sarah Leigh Added comment: Comment on phenotypes: EXT2 variants are also reported in: Seizures, scoliosis, and macrocephaly syndrome, OMIM:616682
Skeletal dysplasia v3.12 EXT2 Sarah Leigh Phenotypes for gene: EXT2 were changed from Exostoses, multiple, type 2 133701 to Exostoses, multiple, type 2 133701
Amyotrophic lateral sclerosis/motor neuron disease v1.67 SPAST Sarah Leigh Publications for gene: SPAST were set to 16832076; 18401025; 33589474
Amyotrophic lateral sclerosis/motor neuron disease v1.66 SPAST Sarah Leigh reviewed gene: SPAST: Rating: GREEN; Mode of pathogenicity: None; Publications: 16240363, 18401025, 33589474; Phenotypes: ; Mode of inheritance: None
Amyotrophic lateral sclerosis/motor neuron disease v1.66 SPAST Sarah Leigh Classified gene: SPAST as Green List (high evidence)
Amyotrophic lateral sclerosis/motor neuron disease v1.66 SPAST Sarah Leigh Gene: spast has been classified as Green List (High Evidence).
Hereditary neuropathy or pain disorder v2.28 SPAST Sarah Leigh Phenotypes for gene: SPAST were changed from Hereditary Neuropathies; Spastic paraplegia 4, autosomal dominant; Spasticity to Spastic paraplegia 4, autosomal dominant, OMIM:182601; hereditary spastic paraplegia 4, MONDO:0008438
Hereditary neuropathy v1.462 SPAST Sarah Leigh Phenotypes for gene: SPAST were changed from Hereditary Neuropathies; Spastic paraplegia 4, autosomal dominant; Spasticity to Spastic paraplegia 4, autosomal dominant, OMIM:182601; hereditary spastic paraplegia 4, MONDO:0008438
Adult onset neurodegenerative disorder v3.59 SPAST Sarah Leigh Phenotypes for gene: SPAST were changed from Spastic paraplegia 4, autosomal dominant, OMIM:182601 to Spastic paraplegia 4, autosomal dominant, OMIM:182601; hereditary spastic paraplegia 4, MONDO:0008438
Adult onset hereditary spastic paraplegia v2.17 SPAST Sarah Leigh Phenotypes for gene: SPAST were changed from Spastic paraplegia 4, autosomal dominant, 182601 to Spastic paraplegia 4, autosomal dominant, OMIM:182601; hereditary spastic paraplegia 4, MONDO:0008438
Childhood onset hereditary spastic paraplegia v3.20 SPAST Sarah Leigh Phenotypes for gene: SPAST were changed from Spastic paraplegia 4, autosomal dominant, 182601 to Spastic paraplegia 4, autosomal dominant, OMIM:182601; hereditary spastic paraplegia 4, MONDO:0008438
Amyotrophic lateral sclerosis/motor neuron disease v1.65 SPAST Sarah Leigh Phenotypes for gene: SPAST were changed from Spastic paraplegia 4, autosomal dominant to Spastic paraplegia 4, autosomal dominant, OMIM:182601; hereditary spastic paraplegia 4, MONDO:0008438
Hereditary spastic paraplegia v1.304 SPAST Sarah Leigh Phenotypes for gene: SPAST were changed from Spastic paraplegia 4, autosomal dominant to Spastic paraplegia 4, autosomal dominant, OMIM:182601; hereditary spastic paraplegia 4, MONDO:0008438
Adult onset neurodegenerative disorder v3.58 NEK1 Sarah Leigh changed review comment from: Associated with Amyotrophic lateral sclerosis, susceptibility to, 24 (OMIM:617892), but not associated with a relevant phenotype in Gen2Phen. At least 12 NEK1 variants have been reported in amyotrophic lateral sclerosis cases (PMID: 30093141; 31768050; 26945885; 27455347), together with supportive functional studies (PMID: 2992911).; to: Associated with Amyotrophic lateral sclerosis, susceptibility to, 24 (OMIM:617892), but not associated with a relevant phenotype in Gen2Phen. At least 12 NEK1 variants have been reported in amyotrophic lateral sclerosis cases (PMID: 30093141; 31768050; 26945885; 27455347), together with supportive functional studies (PMID: 2992911).
ClinGen Definitive gene - disease classification (29/04/2022): https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_bb4f311c-df33-4d9e-8ac6-731b43b93615-2022-04-29T192526.542Z?page=1&size=25&search=
Amyotrophic lateral sclerosis/motor neuron disease v1.64 NEK1 Sarah Leigh Phenotypes for gene: NEK1 were changed from Amyotrophic lateral sclerosis, susceptibility to, 24 to Amyotrophic lateral sclerosis, susceptibility to, 24, OMIM:617892; amyotrophic lateral sclerosis, susceptibility to, 24, MONDO:0054750
Amyotrophic lateral sclerosis/motor neuron disease v1.63 NEK1 Sarah Leigh reviewed gene: NEK1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Amyotrophic lateral sclerosis/motor neuron disease v1.63 NEK1 Sarah Leigh Classified gene: NEK1 as Green List (high evidence)
Amyotrophic lateral sclerosis/motor neuron disease v1.63 NEK1 Sarah Leigh Gene: nek1 has been classified as Green List (High Evidence).
Familial hypoparathyroidism v2.10 TBX1 Arina Puzriakova Classified gene: TBX1 as Amber List (moderate evidence)
Familial hypoparathyroidism v2.10 TBX1 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green on this panel (at least three cases of parathyroid dysfunction, including a patient with isolated hypoparathyroidism) at the next GMS panel update.
Familial hypoparathyroidism v2.10 TBX1 Arina Puzriakova Gene: tbx1 has been classified as Amber List (Moderate Evidence).
Familial hypoparathyroidism v2.9 TBX1 Arina Puzriakova Phenotypes for gene: TBX1 were changed from to DiGeorge syndrome, OMIM:188400; Conotruncal anomaly face syndrome, OMIM:217095; Velocardiofacial syndrome, OMIM:192430
Familial hypoparathyroidism v2.8 TBX1 Arina Puzriakova Publications for gene: TBX1 were set to 30137364
Familial hypoparathyroidism v2.7 TBX1 Arina Puzriakova Tag Q1_23_promote_green tag was added to gene: TBX1.
Familial hypoparathyroidism v2.7 TBX1 Arina Puzriakova reviewed gene: TBX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 14585638, 17273972, 30137364; Phenotypes: DiGeorge syndrome, OMIM:188400, Conotruncal anomaly face syndrome, OMIM:217095, Velocardiofacial syndrome, OMIM:192430; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v4.117 TBX1 Arina Puzriakova reviewed gene: TBX1: Rating: ; Mode of pathogenicity: None; Publications: 14585638, 17273972, 30137364; Phenotypes: ; Mode of inheritance: None
Primary immunodeficiency or monogenic inflammatory bowel disease v3.9 TBX1 Arina Puzriakova Publications for gene: TBX1 were set to 11242110; 32048120; 32086639; 14585638; 24198816; 12548732
Primary immunodeficiency or monogenic inflammatory bowel disease v3.8 TBX1 Arina Puzriakova Classified gene: TBX1 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v3.8 TBX1 Arina Puzriakova Added comment: Comment on list classification: Following consultation with Helen Brittain (Genomics England Clinical Team) it was agreed that there is sufficient evidence to promote this gene to Green on this panel (at least three cases of immune involvement) at the next GMS panel update.
Primary immunodeficiency or monogenic inflammatory bowel disease v3.8 TBX1 Arina Puzriakova Gene: tbx1 has been classified as Amber List (Moderate Evidence).
Clefting v3.9 TBX1 Arina Puzriakova Classified gene: TBX1 as Amber List (moderate evidence)
Clefting v3.9 TBX1 Arina Puzriakova Added comment: Comment on list classification: Following consultation with Helen Brittain (Genomics England Clinical Team) it was agreed that there is sufficient evidence to promote this gene to Green on this panel (at least three cases of palatal involvement) at the next GMS panel update.
Clefting v3.9 TBX1 Arina Puzriakova Gene: tbx1 has been classified as Amber List (Moderate Evidence).
Clefting v3.8 TBX1 Arina Puzriakova Phenotypes for gene: TBX1 were changed from CONOTRUNCAL HEART MALFORMATIONS; CTHM; Cleft palate to DiGeorge syndrome, OMIM:188400; Conotruncal anomaly face syndrome, OMIM:217095; Velocardiofacial syndrome, OMIM:192430
Clefting v3.7 TBX1 Arina Puzriakova Publications for gene: TBX1 were set to
Clefting v3.6 TBX1 Arina Puzriakova Tag Q1_23_promote_green tag was added to gene: TBX1.
Clefting v3.6 TBX1 Arina Puzriakova reviewed gene: TBX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 14585638, 17273972, 30137364; Phenotypes: DiGeorge syndrome, OMIM:188400, Conotruncal anomaly face syndrome, OMIM:217095, Velocardiofacial syndrome, OMIM:192430; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary immunodeficiency or monogenic inflammatory bowel disease v3.7 TBX1 Arina Puzriakova Phenotypes for gene: TBX1 were changed from Hypoparathyroidism, conotruncal cardiac malformation, velopalatal insufficiency, abnormal facies, intellectual disability; Di George syndrome; Severe combined immunodeficiency (SCID); DiGeorge syndrome 188400; T-B+ SCID; Combined immunodeficiencies with associated or syndromic features to DiGeorge syndrome, OMIM:188400; Conotruncal anomaly face syndrome, OMIM:217095; Velocardiofacial syndrome, OMIM:192430
Primary immunodeficiency or monogenic inflammatory bowel disease v3.6 TBX1 Arina Puzriakova Tag Q1_23_promote_green tag was added to gene: TBX1.
Primary immunodeficiency or monogenic inflammatory bowel disease v3.6 TBX1 Arina Puzriakova reviewed gene: TBX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 14585638, 17273972, 30137364; Phenotypes: DiGeorge syndrome, OMIM:188400, Conotruncal anomaly face syndrome, OMIM:217095, Velocardiofacial syndrome, OMIM:192430; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Likely inborn error of metabolism v3.20 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism v3.20 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism v3.20 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v3.19 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism v3.19 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism v3.19 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v3.20 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism v3.20 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism v3.20 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v3.20 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism v3.20 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism v3.20 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v3.20 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism v3.20 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism v3.20 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v3.20 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism v3.20 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism v3.20 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v3.19 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism v3.19 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism v3.19 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v3.19 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism v3.19 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism v3.19 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v3.19 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism v3.19 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism v3.19 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v3.18 GCSH Achchuthan Shanmugasundram Deleted their comment
Likely inborn error of metabolism v3.18 GCSH Achchuthan Shanmugasundram Deleted their comment
Likely inborn error of metabolism v3.18 GCSH Achchuthan Shanmugasundram Deleted their comment
Likely inborn error of metabolism v3.18 GCSH Achchuthan Shanmugasundram Deleted their comment
Likely inborn error of metabolism v3.18 GCSH Achchuthan Shanmugasundram Deleted their comment
Likely inborn error of metabolism v3.18 GCSH Achchuthan Shanmugasundram Deleted their comment
Likely inborn error of metabolism v3.18 GCSH Achchuthan Shanmugasundram Deleted their comment
Likely inborn error of metabolism v3.18 GCSH Achchuthan Shanmugasundram Deleted their comment
Likely inborn error of metabolism v3.18 GCSH Achchuthan Shanmugasundram Deleted their comment
Likely inborn error of metabolism v3.18 GCSH Achchuthan Shanmugasundram Deleted their comment
Likely inborn error of metabolism v3.18 GCSH Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: GCSH.