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Primary lymphoedema v1.113 TSC2 Sarah Leigh Classified gene: TSC2 as Amber List (moderate evidence)
Primary lymphoedema v1.113 TSC2 Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Prof Sahar Mansour (St George's Hospital, London) lymphoedema has been reported with tuberous sclerosis once or twice in the literature and we have a couple of patients but it is rare and there are usually other clues to the diagnosis.
Primary lymphoedema v1.113 TSC2 Sarah Leigh Gene: tsc2 has been classified as Amber List (Moderate Evidence).
Primary lymphoedema v1.112 TSC1 Sarah Leigh Classified gene: TSC1 as Amber List (moderate evidence)
Primary lymphoedema v1.112 TSC1 Sarah Leigh Added comment: Comment on list classification: Based on recommendation from Prof Sahar Mansour (St George's Hospital, London) lymphoedema has been reported with tuberous sclerosis once or twice in the literature and we have a couple of patients but it is rare and there are usually other clues to the diagnosis.
Primary lymphoedema v1.112 TSC1 Sarah Leigh Gene: tsc1 has been classified as Amber List (Moderate Evidence).
Primary lymphoedema v1.111 NSD1 Sarah Leigh Classified gene: NSD1 as Amber List (moderate evidence)
Primary lymphoedema v1.111 NSD1 Sarah Leigh Added comment: Comment on list classification: According to Prof Sahar Mansour (St Georges Hospital, London), lymphoedema has been reported in some cases of Sotos syndrome 1 117550.
Primary lymphoedema v1.111 NSD1 Sarah Leigh Gene: nsd1 has been classified as Amber List (Moderate Evidence).
Primary lymphoedema v1.110 NSD1 Sarah Leigh Phenotypes for gene: NSD1 were changed from to Sotos syndrome 1 117550
Primary lymphoedema v1.109 NSD1 Sarah Leigh Publications for gene: NSD1 were set to 9781911
Primary lymphoedema v1.108 RASA1 Sarah Leigh changed review comment from: Comment on list classification: From Gene Reviews (https://www.ncbi.nlm.nih.gov/books/NBK52764/) "Lymphatic malformations have been reported in several individuals [de Wijn et al 2012, Burrows et al 2013, Macmurdo et al 2016], including one individual with RASA1-related Parkes Weber syndrome. Lymphangiography and near-infrared fluorescence lymphatic imaging showed abnormally dilated collecting lymphatics with sluggish flow in the unaffected limb, and tortuous lymphatics of the affected limb with lymphocele-like vesicles on the groin [Burrows et al 2013]. Whether these lymphatic abnormalities are progressive is not yet known."; to: Comment on list classification: From Gene Reviews (https://www.ncbi.nlm.nih.gov/books/NBK52764/) "Lymphatic malformations have been reported in several individuals [PMIDs 26969842, 23650393, 22342634], including one individual with RASA1-related Parkes Weber syndrome. Lymphangiography and near-infrared fluorescence lymphatic imaging showed abnormally dilated collecting lymphatics with sluggish flow in the unaffected limb, and tortuous lymphatics of the affected limb with lymphocele-like vesicles on the groin [PMID 23650393]. Whether these lymphatic abnormalities are progressive is not yet known."
Primary lymphoedema v1.108 RASA1 Sarah Leigh Classified gene: RASA1 as Amber List (moderate evidence)
Primary lymphoedema v1.108 RASA1 Sarah Leigh Added comment: Comment on list classification: From Gene Reviews (https://www.ncbi.nlm.nih.gov/books/NBK52764/) "Lymphatic malformations have been reported in several individuals [de Wijn et al 2012, Burrows et al 2013, Macmurdo et al 2016], including one individual with RASA1-related Parkes Weber syndrome. Lymphangiography and near-infrared fluorescence lymphatic imaging showed abnormally dilated collecting lymphatics with sluggish flow in the unaffected limb, and tortuous lymphatics of the affected limb with lymphocele-like vesicles on the groin [Burrows et al 2013]. Whether these lymphatic abnormalities are progressive is not yet known."
Primary lymphoedema v1.108 RASA1 Sarah Leigh Gene: rasa1 has been classified as Amber List (Moderate Evidence).
Primary lymphoedema v1.107 RASA1 Sarah Leigh Publications for gene: RASA1 were set to
Primary lymphoedema v1.106 RASA1 Sarah Leigh Phenotypes for gene: RASA1 were changed from to Capillary malformation-arteriovenous malformation 1 608354
Surfactant deficiency v0.26 TERT Matthew Edwards reviewed gene: TERT: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Surfactant deficiency v0.26 SFTPD Matthew Edwards reviewed gene: SFTPD: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: Unknown
Genetic epilepsy syndromes v1.256 KCND2 Alison Callaway reviewed gene: KCND2: Rating: RED; Mode of pathogenicity: None; Publications: 16934482; Phenotypes: ; Mode of inheritance: None
Genetic epilepsy syndromes v1.256 CSNK2A1 Alison Callaway reviewed gene: CSNK2A1: Rating: AMBER; Mode of pathogenicity: None; Publications: 27048600; Phenotypes: Neurodevelopmental abnormalities and dysmorphic features; Mode of inheritance: None
Genetic epilepsy syndromes v1.256 ZNF142 Alison Callaway reviewed gene: ZNF142: Rating: AMBER; Mode of pathogenicity: None; Publications: 31036918; Phenotypes: NEURODEVELOPMENTAL DISORDER WITH IMPAIRED SPEECH AND HYPERKINETIC MOVEMENTS; Mode of inheritance: None
Genetic epilepsy syndromes v1.256 USP7 Alison Callaway reviewed gene: USP7: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Genetic epilepsy syndromes v1.256 TRRAP Alison Callaway reviewed gene: TRRAP: Rating: GREEN; Mode of pathogenicity: None; Publications: 28628100, 30827496; Phenotypes: DEVELOPMENTAL DELAY WITH OR WITHOUT DYSMORPHIC FACIES AND AUTISM; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic epilepsy syndromes v1.256 TRPM3 Alison Callaway reviewed gene: TRPM3: Rating: AMBER; Mode of pathogenicity: None; Publications: 29156220; Phenotypes: ; Mode of inheritance: None
Genetic epilepsy syndromes v1.256 CLCN6 Alison Callaway reviewed gene: CLCN6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Genetic epilepsy syndromes v1.256 AIMP2 Alison Callaway reviewed gene: AIMP2: Rating: AMBER; Mode of pathogenicity: None; Publications: 26795593; Phenotypes: Epileptic Encephalopathy, Infantile Spasms; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v1.256 AFF3 Alison Callaway reviewed gene: AFF3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Genetic epilepsy syndromes v1.256 ALPL Alison Callaway changed review comment from: Epilepsy can be associated with hypophosphasia; no further literature identified. From reviews below, appears to have sufficient evidence for a green gene.; to: Epilepsy can be associated with hypophosphatasia; no further literature identified. From reviews below, appears to have sufficient evidence for a green gene.
Genetic epilepsy syndromes v1.256 ALPL Alison Callaway reviewed gene: ALPL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Genetic epilepsy syndromes v1.256 EMX2 Alison Callaway reviewed gene: EMX2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Genetic epilepsy syndromes v1.256 NPRL2 Alison Callaway reviewed gene: NPRL2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Genetic epilepsy syndromes v1.256 KCNMA1 Alison Callaway reviewed gene: KCNMA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29933521; Phenotypes: Generalised epilepsy and paroxysmal dyskinesia; Mode of inheritance: None
Arrhythmogenic cardiomyopathy v1.25 FLNC Matthew Edwards reviewed gene: FLNC: Rating: GREEN; Mode of pathogenicity: None; Publications: 26666891; Phenotypes: Arrhythmogenic cardiomyopathy, Cardiomyopathy, familial restrictive 5 (OMIM:617047), Myopathy, distal, 4 (OMIM: 614065), Myopathy, myofibrillar, 5 (OMIM:609524; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Genetic epilepsy syndromes v1.256 TUBB2A Alison Callaway reviewed gene: TUBB2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 24702957; Phenotypes: CORTICAL DYSPLASIA, COMPLEX, WITH OTHER BRAIN MALFORMATIONS; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic epilepsy syndromes v1.256 SLC25A12 Alison Callaway reviewed gene: SLC25A12: Rating: GREEN; Mode of pathogenicity: None; Publications: 19641205, 24515575, 27290639, 26633542; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v1.256 HCN2 Alison Callaway reviewed gene: HCN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29064616, 22131395; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic epilepsy syndromes v1.256 HCN2 Alison Callaway Deleted their review
Genetic epilepsy syndromes v1.256 HCN2 Alison Callaway reviewed gene: HCN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29064616, 22131395; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Clefting v1.49 PLEKHA7 Catherine Snow changed review comment from: PMID: 29805042 Cox et al. Identified PLEKHA7 as a potential gene in a cohort of 72 multi generational families with cleft lip with or without cleft palate. 1 likely pathogenic variant (chr11:g.16838582C>T;p.Gly544Asp) was identified in one family. Further analysis of 497 individuals identified a further likely pathogenic variant and another variant of unknown significance both variants were found in the same family (chr11:g.16838676G>A;p.Arg513Trp and chr11:g.16834682T>C;p.Asp662Gly), a further variant of unknown significance was identified in another family. PLEKHA7 has no phenotypes associated in OMIM or disease association in Gene2Phenotype.; to: PMID: 29805042 Cox et al. Identified PLEKHA7 as a potential gene in a cohort of 72 multi generational families with cleft lip with or without cleft palate. 1 likely pathogenic variant (chr11:g.16838582C>T;p.Gly544Asp) was identified in one family. Further analysis of 497 individuals identified a likely pathogenic variant and another variant of unknown significance both variants were found in the same family (chr11:g.16838676G>A;p.Arg513Trp and chr11:g.16834682T>C;p.Asp662Gly), a further variant of unknown significance was identified in another family. PLEKHA7 has no phenotypes associated in OMIM or disease association in Gene2Phenotype.
Clefting v1.49 PLEKHA7 Catherine Snow changed review comment from: PMID: 29805042 Cox et al. Identified PLEKHA7 as a potential gene in a cohort of 72 multi generational families with cleft lip with or without cleft palate. 1 pathogenic variant (chr11:g.16838582C>T;p.Gly544Asp) was identified in one family. Further analysis of 497 individuals identified a further pathogenic variant and another variant of unknown significance both variants were found in the same family (chr11:g.16838676G>A;p.Arg513Trp and chr11:g.16834682T>C;p.Asp662Gly), a further variant of unknown significance was identified in another family. PLEKHA7 has no phenotypes associated in OMIM or disease association in Gene2Phenotype.; to: PMID: 29805042 Cox et al. Identified PLEKHA7 as a potential gene in a cohort of 72 multi generational families with cleft lip with or without cleft palate. 1 likely pathogenic variant (chr11:g.16838582C>T;p.Gly544Asp) was identified in one family. Further analysis of 497 individuals identified a further likely pathogenic variant and another variant of unknown significance both variants were found in the same family (chr11:g.16838676G>A;p.Arg513Trp and chr11:g.16834682T>C;p.Asp662Gly), a further variant of unknown significance was identified in another family. PLEKHA7 has no phenotypes associated in OMIM or disease association in Gene2Phenotype.
Clefting v1.49 PLEKHA5 Catherine Snow changed review comment from: PMID: 29805042 Cox et al. Identified PLEKHA5 as a potential gene in a cohort of 72 multi generational families with cleft lip with or without cleft palate. 1 likely pathogenic de novo variant was identified in one family (chr12:g.19440414A>G;p.Tyr590Cys). Further analysis of 497 individuals identified 5 variants of unknown significance. PLEKHA5 has no phenotypes associated in OMIM or disease association in Gene2Phenotype.; to: PMID: 29805042 Cox et al. Identified PLEKHA5 as a potential gene in a cohort of 72 multi generational families with cleft lip with or without cleft palate. 1 pathogenic de novo variant was identified in one family (chr12:g.19440414A>G;p.Tyr590Cys). Further analysis of 497 individuals identified 5 variants of unknown significance. PLEKHA5 has no phenotypes associated in OMIM or disease association in Gene2Phenotype.
Clefting v1.49 PLEKHA5 Catherine Snow changed review comment from: PMID: 29805042 Cox et al. Identified PLEKHA5 as a potential gene in a cohort of 72 multi generational families with cleft lip with or without cleft palate. 1 pathogenic variant was identified in one family (chr12:g.19440414A>G;p.Tyr590Cys). Further analysis of 497 individuals identified 5 variants of unknown significance. PLEKHA5 has no phenotypes associated in OMIM or disease association in Gene2Phenotype.; to: PMID: 29805042 Cox et al. Identified PLEKHA5 as a potential gene in a cohort of 72 multi generational families with cleft lip with or without cleft palate. 1 likely pathogenic de novo variant was identified in one family (chr12:g.19440414A>G;p.Tyr590Cys). Further analysis of 497 individuals identified 5 variants of unknown significance. PLEKHA5 has no phenotypes associated in OMIM or disease association in Gene2Phenotype.
Undiagnosed metabolic disorders v1.264 ALDH3A2 Sarah Leigh Classified gene: ALDH3A2 as Green List (high evidence)
Undiagnosed metabolic disorders v1.264 ALDH3A2 Sarah Leigh Gene: aldh3a2 has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.263 ALDH3A2 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.263 ALDH3A2 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.263 ALDH3A2 Sarah Leigh Deleted their comment
Clefting v1.49 ESRP2 Catherine Snow Classified gene: ESRP2 as Amber List (moderate evidence)
Clefting v1.49 ESRP2 Catherine Snow Gene: esrp2 has been classified as Amber List (Moderate Evidence).
Undiagnosed metabolic disorders v1.263 ALAS2 Sarah Leigh Classified gene: ALAS2 as Green List (high evidence)
Undiagnosed metabolic disorders v1.263 ALAS2 Sarah Leigh Gene: alas2 has been classified as Green List (High Evidence).
Clefting v1.49 ESRP2 Catherine Snow Classified gene: ESRP2 as Amber List (moderate evidence)
Clefting v1.49 ESRP2 Catherine Snow Gene: esrp2 has been classified as Amber List (Moderate Evidence).
Undiagnosed metabolic disorders v1.262 ALAS2 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.262 ADSL Sarah Leigh Classified gene: ADSL as Green List (high evidence)
Undiagnosed metabolic disorders v1.262 ADSL Sarah Leigh Gene: adsl has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.261 ADSL Sarah Leigh Deleted their comment
Clefting v1.48 ESRP2 Catherine Snow edited their review of gene: ESRP2: Changed rating: AMBER
Undiagnosed metabolic disorders v1.261 ADSL Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.261 ADSL Sarah Leigh Deleted their comment
Clefting v1.48 ESRP2 Catherine Snow edited their review of gene: ESRP2: Added comment: PMID: 29805042 Cox et al. Identified ESRP2 as a potential gene in a cohort of 72 multi generational families with cleft lip with or without cleft palate. 1 likely pathogenic variant (chr16:g.68266284C>T;p.Arg315) was identified in one family. Further analysis of 497 individuals identified a further likely pathogenic variant (chr16:g.68265234G>A;p.Arg520*) in another family. ESRP2 has no phenotypes associated in OMIM or disease association in Gene2Phenotype.; Changed rating: RED
Undiagnosed metabolic disorders v1.261 ADA Sarah Leigh Classified gene: ADA as Green List (high evidence)
Undiagnosed metabolic disorders v1.261 ADA Sarah Leigh Gene: ada has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.260 ADA Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.260 ADA Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.260 ADA Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.260 ADA Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.260 ADA Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.260 ACY1 Sarah Leigh Classified gene: ACY1 as Green List (high evidence)
Undiagnosed metabolic disorders v1.260 ACY1 Sarah Leigh Gene: acy1 has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.259 ACY1 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.259 ACY1 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.259 ABHD12 Sarah Leigh Classified gene: ABHD12 as Green List (high evidence)
Undiagnosed metabolic disorders v1.259 ABHD12 Sarah Leigh Gene: abhd12 has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.258 ABHD12 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.258 ABHD12 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.258 ABHD12 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.258 ABHD12 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.258 ABHD12 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.258 ABHD12 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.258 ABCG8 Sarah Leigh Classified gene: ABCG8 as Green List (high evidence)
Undiagnosed metabolic disorders v1.258 ABCG8 Sarah Leigh Gene: abcg8 has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.257 ABCG8 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.257 ABCG8 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.257 ABCG5 Sarah Leigh Classified gene: ABCG5 as Green List (high evidence)
Undiagnosed metabolic disorders v1.257 ABCG5 Sarah Leigh Gene: abcg5 has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.256 ABCG5 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.256 ALDH3A2 Sarah Leigh edited their review of gene: ALDH3A2: Added comment: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 9 variants reported.; Changed rating: GREEN; Changed publications: 27604308, 10792573, 10577908; Changed phenotypes: Sjogren-Larsson syndrome 270200
Undiagnosed metabolic disorders v1.256 ALAS2 Sarah Leigh edited their review of gene: ALAS2: Added comment: Associated with phenotype in OMIM and not in Gen2Phen. At least 18 variants identified in Anemia, sideroblastic, 1 300751 and two variants in Protoporphyria, erythropoietic, X-linked 300752 in six unrelated families, together with functional studies.; Changed rating: GREEN; Changed publications: 27604308, 1570328, 7560104, 12663458, 18760763; Changed phenotypes: Anemia, sideroblastic, 1 300751, Protoporphyria, erythropoietic, X-linked 300752
Undiagnosed metabolic disorders v1.256 ADSL Sarah Leigh edited their review of gene: ADSL: Added comment: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 8 variants reported associated with adenylosuccinase deficiency in at least 10 unrelated cases.; Changed rating: GREEN; Changed publications: 27604308, 18830228, 12016589, 10090474; Changed phenotypes: Adenylosuccinase deficiency 103050, Intellectual disability, Epileptic encephalopathy
Undiagnosed metabolic disorders v1.256 ADA Sarah Leigh edited their review of gene: ADA: Added comment: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 30 variants reported associated with Adenosine deaminase deficiency.; Changed rating: GREEN; Changed publications: 27604308, 3684597, 2783588, 1680289; Changed phenotypes: Adenosine deaminase deficiency, partial 102700, Severe combined immunodeficiency due to ADA deficiency 102700, Combined B and T cell defect, SCID, Infantile enterocolitis & monogenic inflammatory bowel disease
Undiagnosed metabolic disorders v1.256 ACY1 Sarah Leigh edited their review of gene: ACY1: Added comment: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 7 variants reported in at least 9 unrelated cases.; Changed rating: GREEN; Changed publications: 27604308, 24117009, 17562838, 16465618; Changed phenotypes: Aminoacylase 1 deficiency 609924, Intellectual disability
Undiagnosed metabolic disorders v1.256 ABHD12 Sarah Leigh edited their review of gene: ABHD12: Added comment: Associated with phenotype in OMIM and not in Gen2Phen. At least 7 variants identified in at least 6 unrelated cases; Changed rating: GREEN; Changed publications: 27604308, 20797687, 24697911 ; Changed phenotypes: Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract 612674, Hereditary ataxia, Posterior segment abnormalities, Congenital hearing impairment (profound/severe), PHARC syndrome (Disorders of complex lipid synthesis)
Undiagnosed metabolic disorders v1.256 ABCG8 Sarah Leigh edited their review of gene: ABCG8: Added comment: Associated with phenotype in OMIM and not in Gen2Phen. At least 9 variants identified in numberous unrelated cases; Changed rating: GREEN; Changed publications: 27604308, 11452359, 15996216, 11099417, 22981120; Changed phenotypes: Sitosterolemia 210250, Familial hypercholesterolaemia
Undiagnosed metabolic disorders v1.256 ABCG5 Sarah Leigh edited their review of gene: ABCG5: Added comment: Associated with phenotype in OMIM and not in Gen2Phen. At least 8 variants identified in unrelated cases; Changed rating: GREEN; Changed publications: 27604308, 11099417, 11138003, 20719861, 17976197; Changed phenotypes: Sitosterolemia 210250, Familial hypercholesterolaemia
Clefting v1.48 ESRP2 Catherine Snow gene: ESRP2 was added
gene: ESRP2 was added to Clefting. Sources: Expert list
Mode of inheritance for gene: ESRP2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ESRP2 were set to 29805042
Phenotypes for gene: ESRP2 were set to cleft lip
Added comment: Gene suggested for the panel by Andrew Wilkie, Oxford University Hospitals NHS Foundation Trust
Sources: Expert list
Clefting v1.47 PLEKHA7 Catherine Snow changed review comment from: PMID: 29805042 Cox et al. Identified PLEKHA7 as a potential gene in a cohort of 72 multi generational families with cleft lip with or without cleft palate. 1 pathogenic variant was identified in one family. Further analysis of 497 individuals identified a further pathogenic variant and another variant of unknown significance both variants were found in the same family, a further variant of unknown significance was identified in a family. PLEKHA7 has no phenotypes associated in OMIM or disease association in Gene2Phenotype.; to: PMID: 29805042 Cox et al. Identified PLEKHA7 as a potential gene in a cohort of 72 multi generational families with cleft lip with or without cleft palate. 1 pathogenic variant (chr11:g.16838582C>T;p.Gly544Asp) was identified in one family. Further analysis of 497 individuals identified a further pathogenic variant and another variant of unknown significance both variants were found in the same family (chr11:g.16838676G>A;p.Arg513Trp and chr11:g.16834682T>C;p.Asp662Gly), a further variant of unknown significance was identified in another family. PLEKHA7 has no phenotypes associated in OMIM or disease association in Gene2Phenotype.
Inborn errors of metabolism v1.262 ALAS2 Sarah Leigh Classified gene: ALAS2 as Green List (high evidence)
Inborn errors of metabolism v1.262 ALAS2 Sarah Leigh Gene: alas2 has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.261 ADSL Sarah Leigh Classified gene: ADSL as Green List (high evidence)
Inborn errors of metabolism v1.261 ADSL Sarah Leigh Gene: adsl has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.260 ALAS2 Sarah Leigh Deleted their comment
Inborn errors of metabolism v1.260 ADSL Sarah Leigh Deleted their comment
Clefting v1.47 PLEKHA5 Catherine Snow edited their review of gene: PLEKHA5: Added comment: PMID: 29805042 Cox et al. Identified PLEKHA5 as a potential gene in a cohort of 72 multi generational families with cleft lip with or without cleft palate. 1 pathogenic variant was identified in one family (chr12:g.19440414A>G;p.Tyr590Cys). Further analysis of 497 individuals identified 5 variants of unknown significance. PLEKHA5 has no phenotypes associated in OMIM or disease association in Gene2Phenotype.; Changed rating: RED
Inborn errors of metabolism v1.260 ABHD12 Sarah Leigh Classified gene: ABHD12 as Green List (high evidence)
Inborn errors of metabolism v1.260 ABHD12 Sarah Leigh Gene: abhd12 has been classified as Green List (High Evidence).
Clefting v1.47 PLEKHA7 Catherine Snow changed review comment from: PMID: 29805042 Cox et al. Identified PLEKHA7 as a potential gene in a cohort of 72 multi generational families with cleft lip with or without cleft palate. 1 pathogenic variant was identified in one family. Further analysis of 497 individuals identified a further pathogenic variant and another variant of unknown significance both variants were found in the same family. PLEKHA7 has no phenotypes associated in OMIM or disease association in Gene2Phenotype.; to: PMID: 29805042 Cox et al. Identified PLEKHA7 as a potential gene in a cohort of 72 multi generational families with cleft lip with or without cleft palate. 1 pathogenic variant was identified in one family. Further analysis of 497 individuals identified a further pathogenic variant and another variant of unknown significance both variants were found in the same family, a further variant of unknown significance was identified in a family. PLEKHA7 has no phenotypes associated in OMIM or disease association in Gene2Phenotype.
Inborn errors of metabolism v1.259 ADA Sarah Leigh Classified gene: ADA as Green List (high evidence)
Inborn errors of metabolism v1.259 ADA Sarah Leigh Gene: ada has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.259 ACY1 Sarah Leigh Classified gene: ACY1 as Green List (high evidence)
Inborn errors of metabolism v1.259 ACY1 Sarah Leigh Gene: acy1 has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.258 ADA Sarah Leigh Deleted their comment
Inborn errors of metabolism v1.258 ABHD12 Sarah Leigh Classified gene: ABHD12 as Green List (high evidence)
Inborn errors of metabolism v1.258 ABHD12 Sarah Leigh Gene: abhd12 has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.258 ACY1 Sarah Leigh Deleted their comment
Inborn errors of metabolism v1.258 ABCG8 Sarah Leigh Classified gene: ABCG8 as Green List (high evidence)
Inborn errors of metabolism v1.258 ABCG8 Sarah Leigh Gene: abcg8 has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.257 ABHD12 Sarah Leigh Deleted their comment
Inborn errors of metabolism v1.257 ABCG8 Sarah Leigh Deleted their comment
Inborn errors of metabolism v1.257 ABCG5 Sarah Leigh Classified gene: ABCG5 as Green List (high evidence)
Inborn errors of metabolism v1.257 ABCG5 Sarah Leigh Gene: abcg5 has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.256 ABCG5 Sarah Leigh Deleted their comment
Clefting v1.47 PLEKHA5 Catherine Snow gene: PLEKHA5 was added
gene: PLEKHA5 was added to Clefting. Sources: Expert list
Mode of inheritance for gene: PLEKHA5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PLEKHA5 were set to 29805042
Phenotypes for gene: PLEKHA5 were set to cleft lip
Added comment: Gene suggested for the panel by Andrew Wilkie, Oxford University Hospitals NHS Foundation Trust
Sources: Expert list
Inborn errors of metabolism v1.256 ABCG5 Sarah Leigh changed review comment from: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.Associated with phenotype in OMIM and not in Gen2Phen. At least 8 variants identified in unrelated cases; to: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.Associated with phenotype in OMIM and not in Gen2Phen. At least 8 variants identified in unrelated cases
Inborn errors of metabolism v1.256 ALDH3A2 Sarah Leigh Classified gene: ALDH3A2 as Green List (high evidence)
Inborn errors of metabolism v1.256 ALDH3A2 Sarah Leigh Gene: aldh3a2 has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.255 ALDH3A2 Sarah Leigh Deleted their comment
Clefting v1.46 PLEKHA7 Catherine Snow Classified gene: PLEKHA7 as Amber List (moderate evidence)
Clefting v1.46 PLEKHA7 Catherine Snow Gene: plekha7 has been classified as Amber List (Moderate Evidence).
Inborn errors of metabolism v1.255 ALDH3A2 Sarah Leigh commented on gene: ALDH3A2: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 9 variants reported.
Inborn errors of metabolism v1.255 ALAS2 Sarah Leigh commented on gene: ALAS2: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with phenotype in OMIM and not in Gen2Phen. At least 18 variants identified in Anemia, sideroblastic, 1 300751 and two variants in Protoporphyria, erythropoietic, X-linked 300752 in six unrelated families, together with functional studies.
Inborn errors of metabolism v1.255 ADSL Sarah Leigh commented on gene: ADSL: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 8 variants reported associated with adenylosuccinase deficiency in at least 10 unrelated cases.
Inborn errors of metabolism v1.255 ADA Sarah Leigh commented on gene: ADA: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 30 variants reported associated with Adenosine deaminase deficiency.
Inborn errors of metabolism v1.255 ACY1 Sarah Leigh commented on gene: ACY1: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 7 variants reported in at least 9 unrelated cases.
Inborn errors of metabolism v1.255 ABHD12 Sarah Leigh commented on gene: ABHD12: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with phenotype in OMIM and not in Gen2Phen. At least 7 variants identified in at least 6 unrelated cases
Inborn errors of metabolism v1.255 ABCG8 Sarah Leigh commented on gene: ABCG8: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.Associated with phenotype in OMIM and not in Gen2Phen. At least 9 variants identified in numberous unrelated cases
Inborn errors of metabolism v1.255 ABCG5 Sarah Leigh commented on gene: ABCG5: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.Associated with phenotype in OMIM and not in Gen2Phen. At least 8 variants identified in unrelated cases
Clefting v1.45 PLEKHA7 Catherine Snow commented on gene: PLEKHA7: PMID: 29805042 Cox et al. Identified PLEKHA7 as a potential gene in a cohort of 72 multi generational families with cleft lip with or without cleft palate. 1 pathogenic variant was identified in one family. Further analysis of 497 individuals identified a further pathogenic variant and another variant of unknown significance both variants were found in the same family. PLEKHA7 has no phenotypes associated in OMIM or disease association in Gene2Phenotype.
Inborn errors of metabolism v1.254 ALDH3A2 Sarah Leigh reviewed gene: ALDH3A2: Rating: GREEN; Mode of pathogenicity: ; Publications: 27604308, 10792573, 10577908; Phenotypes: Sjogren-Larsson syndrome 270200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Inborn errors of metabolism v1.254 ALAS2 Sarah Leigh edited their review of gene: ALAS2: Added comment: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with phenotype in OMIM and not in Gen2Phen. At least 18 variants identified in Anemia, sideroblastic, 1 300751 and two variants in Protoporphyria, erythropoietic, X-linked 300752 in six unrelated families, together with functional studies.; Changed rating: GREEN; Changed publications: 27604308, 1570328, 7560104, 12663458, 18760763; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Inborn errors of metabolism v1.254 ADSL Sarah Leigh reviewed gene: ADSL: Rating: GREEN; Mode of pathogenicity: ; Publications: 27604308, 18830228, 12016589, 10090474; Phenotypes: Adenylosuccinase deficiency 103050, Intellectual disability, Epileptic encephalopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Inborn errors of metabolism v1.254 ADA Sarah Leigh reviewed gene: ADA: Rating: GREEN; Mode of pathogenicity: ; Publications: 27604308, 3684597, 2783588, 1680289; Phenotypes: Adenosine deaminase deficiency, partial 102700, Severe combined immunodeficiency due to ADA deficiency 102700, Combined B and T cell defect, SCID, Infantile enterocolitis & monogenic inflammatory bowel disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Inborn errors of metabolism v1.254 ACY1 Sarah Leigh reviewed gene: ACY1: Rating: GREEN; Mode of pathogenicity: ; Publications: 27604308, 24117009, 17562838, 16465618; Phenotypes: Aminoacylase 1 deficiency 609924, Intellectual disability; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Inborn errors of metabolism v1.254 ABHD12 Sarah Leigh reviewed gene: ABHD12: Rating: GREEN; Mode of pathogenicity: ; Publications: 27604308, 20797687, 24697911 ; Phenotypes: Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract 612674, Hereditary ataxia, Posterior segment abnormalities, Congenital hearing impairment (profound/severe), PHARC syndrome (Disorders of complex lipid synthesis); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Inborn errors of metabolism v1.254 ABCG8 Sarah Leigh reviewed gene: ABCG8: Rating: GREEN; Mode of pathogenicity: ; Publications: 27604308, 11452359, 15996216, 11099417, 22981120; Phenotypes: Sitosterolemia 210250, Familial hypercholesterolaemia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Inborn errors of metabolism v1.254 ABCG5 Sarah Leigh reviewed gene: ABCG5: Rating: GREEN; Mode of pathogenicity: ; Publications: 27604308, 11099417, 11138003, 20719861, 17976197; Phenotypes: Sitosterolemia 210250, Familial hypercholesterolaemia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Clefting v1.45 PLEKHA7 Catherine Snow gene: PLEKHA7 was added
gene: PLEKHA7 was added to Clefting. Sources: Expert list
Mode of inheritance for gene: PLEKHA7 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PLEKHA7 were set to 29805042
Phenotypes for gene: PLEKHA7 were set to cleft lip
Review for gene: PLEKHA7 was set to AMBER
Added comment: Gene suggested for the panel by Andrew Wilkie, Oxford University Hospitals NHS Foundation Trust
Sources: Expert list
Mitochondrial disorders v1.485 USMG5 Sarah Leigh Tag founder-effect tag was added to gene: USMG5.
Mitochondrial disorders v1.485 USMG5 Sarah Leigh edited their review of gene: USMG5: Changed rating: AMBER
Mitochondrial disorders v1.485 IARS Sarah Leigh edited their review of gene: IARS: Changed rating: AMBER
Mitochondrial disorders v1.485 PLA2G6 Sarah Leigh edited their review of gene: PLA2G6: Changed rating: AMBER
Undiagnosed metabolic disorders v1.255 PSPH Sarah Leigh Added comment: Comment on phenotypes: Phosphoserine phosphatase deficiency (Disorders of serine, glycine or glycerate metabolism)
Undiagnosed metabolic disorders v1.255 PSPH Sarah Leigh Phenotypes for gene: PSPH were changed from Phosphoserine phosphatase deficiency (Disorders of serine, glycine or glycerate metabolism); Intellectual disability; Unexplained skeletal dysplasia to Phosphoserine phosphatase deficiency 614023
Inborn errors of metabolism v1.253 PSPH Sarah Leigh Added comment: Comment on phenotypes: Phosphoserine phosphatase deficiency (Disorders of serine, glycine or glycerate metabolism)
Inborn errors of metabolism v1.253 PSPH Sarah Leigh Phenotypes for gene: PSPH were changed from Intellectual disability; Phosphoserine phosphatase deficiency (Disorders of serine, glycine or glycerate metabolism); Unexplained skeletal dysplasia to Phosphoserine phosphatase deficiency 614023
Undiagnosed metabolic disorders v1.254 PSPH Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.254 PSPH Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.254 PSPH Sarah Leigh Deleted their comment
Inborn errors of metabolism v1.252 PSAT1 Sarah Leigh Classified gene: PSAT1 as Green List (high evidence)
Inborn errors of metabolism v1.252 PSAT1 Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM and as probable Gen2Phen gene for ?Phosphoserine aminotransferase deficiency 610992; Neu-Laxova syndrome 2 616038. At least 5 variants reported in 6 cases of Neu-Laxova syndrome 2 616038 and 2 variants in a case of ?Phosphoserine aminotransferase deficiency 610992.
Inborn errors of metabolism v1.252 PSAT1 Sarah Leigh Gene: psat1 has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.254 PSAT1 Sarah Leigh Classified gene: PSAT1 as Green List (high evidence)
Undiagnosed metabolic disorders v1.254 PSAT1 Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene for ?Phosphoserine aminotransferase deficiency 610992; Neu-Laxova syndrome 2 616038. At least 5 variants reported in 6 cases of Neu-Laxova syndrome 2 616038 and 2 variants in a case of ?Phosphoserine aminotransferase deficiency 610992.
Undiagnosed metabolic disorders v1.254 PSAT1 Sarah Leigh Gene: psat1 has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.251 PSAT1 Sarah Leigh Publications for gene: PSAT1 were set to 27604308
Undiagnosed metabolic disorders v1.253 PSAT1 Sarah Leigh Publications for gene: PSAT1 were set to 27604308
Inborn errors of metabolism v1.250 PSAT1 Sarah Leigh Added comment: Comment on phenotypes: Phosphoserine aminotransferase deficiency (Disorders of serine, glycine or glycerate metabolism)
Inborn errors of metabolism v1.250 PSAT1 Sarah Leigh Phenotypes for gene: PSAT1 were changed from Phosphoserine aminotransferase deficiency (Disorders of serine, glycine or glycerate metabolism); Unexplained skeletal dysplasia to ?Phosphoserine aminotransferase deficiency 610992; Neu-Laxova syndrome 2 616038
Undiagnosed metabolic disorders v1.252 PSAT1 Sarah Leigh Added comment: Comment on phenotypes: Phosphoserine aminotransferase deficiency (Disorders of serine, glycine or glycerate metabolism)
Undiagnosed metabolic disorders v1.252 PSAT1 Sarah Leigh Phenotypes for gene: PSAT1 were changed from Phosphoserine aminotransferase deficiency (Disorders of serine, glycine or glycerate metabolism); Unexplained skeletal dysplasia to ?Phosphoserine aminotransferase deficiency 610992; Neu-Laxova syndrome 2 616038
Undiagnosed metabolic disorders v1.251 PSAT1 Sarah Leigh Deleted their comment
Inborn errors of metabolism v1.249 PRPS1 Sarah Leigh Added comment: Comment on phenotypes: Phosphoribosyl pyrophosphate synthetase 1 defects (Disorders of purine metabolism)
Inborn errors of metabolism v1.249 PRPS1 Sarah Leigh Phenotypes for gene: PRPS1 were changed from Intellectual disability; Charcot-Marie-Tooth disease; Phosphoribosyl pyrophosphate synthetase 1 defects (Disorders of purine metabolism); Congenital hearing impairment (profound/severe); Intellectual_disability to Arts syndrome 301835; Charcot-Marie-Tooth disease, X-linked recessive, 5 311070; Deafness, X-linked 1 304500; Gout, PRPS-related 300661; Phosphoribosylpyrophosphate synthetase superactivity 300661
Inborn errors of metabolism v1.248 PRPS1 Sarah Leigh Classified gene: PRPS1 as Green List (high evidence)
Inborn errors of metabolism v1.248 PRPS1 Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene for Arts syndrome 301835, Charcot-Marie-Tooth disease, X-linked recessive, 5 311070, Deafness, X-linked 1 304500 and Phosphoribosylpyrophosphate synthetase superactivity 300661. At least 22 variants have been reported across the phenotypes.
Inborn errors of metabolism v1.248 PRPS1 Sarah Leigh Gene: prps1 has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.251 PRPS1 Sarah Leigh Classified gene: PRPS1 as Green List (high evidence)
Undiagnosed metabolic disorders v1.251 PRPS1 Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene for Arts syndrome 301835, Charcot-Marie-Tooth disease, X-linked recessive, 5 311070, Deafness, X-linked 1 304500 and Phosphoribosylpyrophosphate synthetase superactivity 300661. At least 22 variants have been reported across the phenotypes.
Undiagnosed metabolic disorders v1.251 PRPS1 Sarah Leigh Gene: prps1 has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.250 PRPS1 Sarah Leigh Added comment: Comment on phenotypes: Phosphoribosyl pyrophosphate synthetase 1 defects (Disorders of purine metabolism)
Undiagnosed metabolic disorders v1.250 PRPS1 Sarah Leigh Phenotypes for gene: PRPS1 were changed from Phosphoribosyl pyrophosphate synthetase 1 defects (Disorders of purine metabolism); Charcot-Marie-Tooth disease; Congenital hearing impairment (profound/severe); Intellectual disability; Intellectual_disability to Arts syndrome 301835; Charcot-Marie-Tooth disease, X-linked recessive, 5 311070; Deafness, X-linked 1 304500; Gout, PRPS-related 300661; Phosphoribosylpyrophosphate synthetase superactivity 300661
Inborn errors of metabolism v1.247 PRPS1 Sarah Leigh Mode of inheritance for gene: PRPS1 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
Undiagnosed metabolic disorders v1.249 PRPS1 Sarah Leigh Mode of inheritance for gene: PRPS1 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
Cardiomyopathies - including childhood onset v1.35 PRPS1 Sarah Leigh Mode of inheritance for gene: PRPS1 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
Primary lymphoedema v1.105 MPI Sarah Leigh changed review comment from: PMI is old gene name (15q24.1-.2) is associated with Congenital disorder of glycosylation, type Ib 602579, which includes lymphangiectasia. The gene submitted on expert list was PM1 (new gene name TMEM11 (17p11.1), this is not on OMIM and not associated with condition on G2P).; to: PMI is old gene name (15q24.1-.2) is associated with Congenital disorder of glycosylation, type Ib 602579, which includes lymphangiectasia. The gene submitted on expert list was PM1 (new gene name TMEM11 (17p11.1), this is not on OMIM and not associated with a condition on G2P).
Primary lymphoedema v1.105 MPI Sarah Leigh changed review comment from: PMI is old gene name ( 15q24.1-.2) is associated with Congenital disorder of glycosylation, type Ib 602579, which includes lymphangiectasia. The gene submitted on expert list was PM1 (new gene name TMEM11 (17p11.1), this is not on OMIM and not associated with condition on G2P).; to: PMI is old gene name (15q24.1-.2) is associated with Congenital disorder of glycosylation, type Ib 602579, which includes lymphangiectasia. The gene submitted on expert list was PM1 (new gene name TMEM11 (17p11.1), this is not on OMIM and not associated with condition on G2P).
Cytopenia - NOT Fanconi anaemia v0.119 Louise Daugherty List of related panels changed from to R91
Primary lymphoedema v1.105 CELSR1 Sarah Leigh Penetrance for gene CELSR1 was set from to None
Primary lymphoedema v1.104 CELSR1 Sarah Leigh Classified gene: CELSR1 as Green List (high evidence)
Primary lymphoedema v1.104 CELSR1 Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 7 variants reported, showing incomplete penetrance, whereby male carries did not manifest with lymphoedema except in later life (PMID 31215153).
Primary lymphoedema v1.104 CELSR1 Sarah Leigh Gene: celsr1 has been classified as Green List (High Evidence).
Primary lymphoedema v1.103 CELSR1 Sarah Leigh gene: CELSR1 was added
gene: CELSR1 was added to Primary lymphoedema. Sources: Expert list
Mode of inheritance for gene: CELSR1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CELSR1 were set to 31403174; 26855770; 31215153
Phenotypes for gene: CELSR1 were set to hereditary lymphedema
Review for gene: CELSR1 was set to GREEN
Added comment: Sources: Expert list
Thrombophilia v0.40 Louise Daugherty List of related panels changed from to R97
Rare anaemia v0.77 Louise Daugherty List of related panels changed from to R92
Iron metabolism disorders v0.54 Louise Daugherty List of related panels changed from to R96
Primary lymphoedema v1.102 CHD7 Sarah Leigh Publications for gene: CHD7 were set to
Primary lymphoedema v1.101 CHD7 Sarah Leigh Added comment: Comment on phenotypes: Variants are also associated with Hypogonadotropic hypogonadism 5 with or without anosmia 612370, but this is not relevant to this panel.
Primary lymphoedema v1.101 CHD7 Sarah Leigh Phenotypes for gene: CHD7 were changed from CHARGE syndrome 214800 to CHARGE syndrome 214800
Primary lymphoedema v1.100 CHD7 Sarah Leigh Classified gene: CHD7 as Green List (high evidence)
Primary lymphoedema v1.100 CHD7 Sarah Leigh Gene: chd7 has been classified as Green List (High Evidence).
Primary lymphoedema v1.99 CHD7 Sarah Leigh gene: CHD7 was added
gene: CHD7 was added to Primary lymphoedema. Sources: Expert list
Mode of inheritance for gene: CHD7 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: CHD7 were set to CHARGE syndrome 214800
Review for gene: CHD7 was set to GREEN
Added comment: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene for CHARGE syndrome 214800. At least 14 variants reported associated with CHARGE syndrome 214800.
Sources: Expert list
Primary lymphoedema v1.98 Sarah Leigh removed gene:CDH7 from the panel
Confirmed Fanconi anaemia or Bloom syndrome v0.28 Louise Daugherty List of related panels changed from to R229
Combined factor V and VIII deficiency v0.22 Louise Daugherty List of related panels changed from to R124
Inherited predisposition to acute myeloid leukaemia (AML) v0.47 Louise Daugherty List of related panels changed from to R347
Bleeding and platelet disorders v0.77 COL5A2 Louise Daugherty commented on gene: COL5A2: The Specialist Test Group discussed the inclusion of EDS genes on this panel and if included, what rating they should be. EDS genes are currently all rated as Amber until further discussion with EDS experts
Bleeding and platelet disorders v0.77 COL5A1 Louise Daugherty commented on gene: COL5A1: The Specialist Test Group discussed the inclusion of EDS genes on this panel and if included, what rating they should be. EDS genes are currently all rated as Amber until further discussion with EDS experts
Bleeding and platelet disorders v0.77 CHST14 Louise Daugherty commented on gene: CHST14: The Specialist Test Group discussed the inclusion of EDS genes on this panel and if included, what rating they should be. EDS genes are currently all rated as Amber until further discussion with EDS experts
Bleeding and platelet disorders v0.77 COL3A1 Louise Daugherty commented on gene: COL3A1: The Specialist Test Group discussed the inclusion of EDS genes on this panel and if included, what rating they should be. EDS genes are currently all rated as Amber until further discussion with EDS experts
Bleeding and platelet disorders v0.77 COL1A1 Louise Daugherty commented on gene: COL1A1: The Specialist Test Group discussed the inclusion of EDS genes on this panel and if included, what rating they should be. EDS genes are currently all rated as Amber until further discussion with EDS experts
Bleeding and platelet disorders v0.77 TNXB Louise Daugherty changed review comment from: Added to panel from suggestion from Neeti Ghali in view of including EDS genes on the R60 panel. TNXB is another (AR) EDS type presenting with significant bruising/haematomas, but again, other features are usually present. To be discussed further as to the rating and in view of the other EDS genes on this panel (COL1A1, COL3A1, COL5A1, COL5A2, CHST14)
Sources: Expert Review; to: Added to panel from suggestion from Neeti Ghali in view of including EDS genes on the R60 panel. TNXB is another (AR) EDS type presenting with significant bruising/haematomas, but again, other features are usually present. To be discussed further with Haematology Test Group as to the rating and in view of the other EDS genes on this panel (COL1A1, COL3A1, COL5A1, COL5A2, CHST14)
Sources: Expert Review
Bleeding and platelet disorders v0.77 ETV6 Louise Daugherty Deleted their comment
Mitochondrial disorders v1.485 PLA2G6 Sarah Leigh changed review comment from: Associated with relevant phenotype in OMIM and as a both DD and IF Gen2Phen gene. At least numerous variants reported. The GMS mitochondrial specialist test group should be consultated on this gene with respect to phenotype (comments from Anna de Burca, Genomics England Clinical Fellow). ; to: Associated with relevant phenotype in OMIM and as a both DD and IF Gen2Phen gene. Numerous variants reported. The GMS mitochondrial specialist test group should be consultated on this gene with respect to phenotype (comments from Anna de Burca, Genomics England Clinical Fellow). 
Bleeding and platelet disorders v0.77 TNXB Louise Daugherty Publications for gene: TNXB were set to
Bleeding and platelet disorders v0.76 TNXB Louise Daugherty Classified gene: TNXB as Amber List (moderate evidence)
Bleeding and platelet disorders v0.76 TNXB Louise Daugherty Gene: tnxb has been classified as Amber List (Moderate Evidence).
Bleeding and platelet disorders v0.75 TNXB Louise Daugherty Classified gene: TNXB as No list
Bleeding and platelet disorders v0.75 TNXB Louise Daugherty Gene: tnxb has been removed from the panel.
Bleeding and platelet disorders v0.74 TNXB Louise Daugherty gene: TNXB was added
gene: TNXB was added to Bleeding and platelet disorders. Sources: Expert Review
Mode of inheritance for gene: TNXB was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TNXB were set to Ehlers-Danlos syndrome due to tenascin X deficiency, 606408; significant bruising/haematomas
Review for gene: TNXB was set to AMBER
Added comment: Added to panel from suggestion from Neeti Ghali in view of including EDS genes on the R60 panel. TNXB is another (AR) EDS type presenting with significant bruising/haematomas, but again, other features are usually present. To be discussed further as to the rating and in view of the other EDS genes on this panel (COL1A1, COL3A1, COL5A1, COL5A2, CHST14)
Sources: Expert Review
Bleeding and platelet disorders v0.73 Louise Daugherty List of related panels changed from to R90
Laterality disorders and isomerism v0.42 Louise Daugherty List of related panels changed from to R139
Surfactant deficiency v0.26 Louise Daugherty List of related panels changed from to R192
Pneumothorax - familial v1.17 Louise Daugherty List of related panels changed from Familial Pneumothorax; Familial Primary Spontaneous Pneumothorax to Familial Pneumothorax; Familial Primary Spontaneous Pneumothorax; R190
Respiratory ciliopathies including non-CF bronchiectasis v0.151 Louise Daugherty List of related panels changed from to R189
Primary immunodeficiency v1.54 Louise Daugherty List of related panels changed from Primary immunodeficiency disorders; A- or hypo-gammaglobulinaemia; Congenital neutropaenia; Agranulocytosis; Combined B and T cell defect; Inherited complement deficiency; SCID; Primary immune disorder; Primary immunodeficiency; A-gammaglobulinaemia; Agammaglobulinaemia; hypo-gammaglobulinaemia; hypogammaglobulinemia; immune deficiency syndromes; Severe combined immunodeficiency; Congenital neutopenia; Familial haemophagocytic lymphohistiocytic disorders; Familial hemophagocytic lymphohistiocytic disorders; PID; Sepsis; Disseminated non-tuberculous mycobacterial infection to Primary immunodeficiency disorders; A- or hypo-gammaglobulinaemia; Congenital neutropaenia; Agranulocytosis; Combined B and T cell defect; Inherited complement deficiency; SCID; Primary immune disorder; Primary immunodeficiency; A-gammaglobulinaemia; Agammaglobulinaemia; hypo-gammaglobulinaemia; hypogammaglobulinemia; immune deficiency syndromes; Severe combined immunodeficiency; Congenital neutopenia; Familial haemophagocytic lymphohistiocytic disorders; Familial hemophagocytic lymphohistiocytic disorders; PID; Sepsis; Disseminated non-tuberculous mycobacterial infection; R15
Inborn errors of metabolism v1.246 GATC Sarah Leigh Deleted their comment
Inborn errors of metabolism v1.246 GATC Sarah Leigh Deleted their comment
Inborn errors of metabolism v1.246 GATC Sarah Leigh Classified gene: GATC as Amber List (moderate evidence)
Inborn errors of metabolism v1.246 GATC Sarah Leigh Added comment: Comment on list classification: This rating is based on the evidence that GATB, GATC & QRSL1 are functioning together in the development of this condition.
Inborn errors of metabolism v1.246 GATC Sarah Leigh Gene: gatc has been classified as Amber List (Moderate Evidence).
Inborn errors of metabolism v1.245 GATC Sarah Leigh Classified gene: GATC as Amber List (moderate evidence)
Inborn errors of metabolism v1.245 GATC Sarah Leigh Added comment: Comment on list classification: This rating is based on the evidence that GATB, GATC & QRSL1 are functioning together in the development of this condition.
Inborn errors of metabolism v1.245 GATC Sarah Leigh Gene: gatc has been classified as Amber List (Moderate Evidence).
Inborn errors of metabolism v1.245 GATC Sarah Leigh Classified gene: GATC as Amber List (moderate evidence)
Inborn errors of metabolism v1.245 GATC Sarah Leigh Added comment: Comment on list classification: This rating is based on the evidence that GATB, GATC & QRSL1 are functioning together in the development of this condition.
Inborn errors of metabolism v1.245 GATC Sarah Leigh Gene: gatc has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v1.485 GATC Sarah Leigh Classified gene: GATC as Amber List (moderate evidence)
Mitochondrial disorders v1.485 GATC Sarah Leigh Added comment: Comment on list classification: This rating is based on the evidence that GATB, GATC & QRSL1 are functioning together in the development of this condition.
Mitochondrial disorders v1.485 GATC Sarah Leigh Gene: gatc has been classified as Amber List (Moderate Evidence).
Inborn errors of metabolism v1.244 GATC Sarah Leigh Publications for gene: GATC were set to
Mitochondrial disorders v1.484 GATC Sarah Leigh Publications for gene: GATC were set to
Mitochondrial disorders v1.483 GATB Sarah Leigh Publications for gene: GATB were set to
Mitochondrial disorders v1.482 GATB Sarah Leigh Classified gene: GATB as Amber List (moderate evidence)
Mitochondrial disorders v1.482 GATB Sarah Leigh Added comment: Comment on list classification: This rating is based on the evidence that GATB, GATC & QRSL1 are functioning together in the development of this condition.
Mitochondrial disorders v1.482 GATB Sarah Leigh Gene: gatb has been classified as Amber List (Moderate Evidence).
Undiagnosed metabolic disorders v1.248 ATP5A1 Sarah Leigh Publications for gene: ATP5A1 were set to 27604308
Undiagnosed metabolic disorders v1.247 ATP5A1 Sarah Leigh Classified gene: ATP5A1 as Amber List (moderate evidence)
Undiagnosed metabolic disorders v1.247 ATP5A1 Sarah Leigh Added comment: Comment on list classification: Two variants together with functional studies. The Amber rating is based on the views of Anna de Burca (Genomics England Clinical Fellow) that the interpretation of PMID 23599390 that the boys have inherited a heterozygous variant from their father while not expressing the maternal allele due to unknown variant affecting expression.
Undiagnosed metabolic disorders v1.247 ATP5A1 Sarah Leigh Gene: atp5a1 has been classified as Amber List (Moderate Evidence).
Mitochondrial disorder with complex V deficiency v1.0 ATP5A1 Sarah Leigh reviewed gene: ATP5A1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Inborn errors of metabolism v1.243 ATP5A1 Sarah Leigh Classified gene: ATP5A1 as Amber List (moderate evidence)
Inborn errors of metabolism v1.243 ATP5A1 Sarah Leigh Added comment: Comment on list classification: The Amber rating is based on the views of Anna de Burca (Genomics England Clinical Fellow) that the interpretation of PMID 23599390 that the boys have inherited a heterozygous variant from their father while not expressing the maternal allele due to unknown variant affecting expression.
Inborn errors of metabolism v1.243 ATP5A1 Sarah Leigh Gene: atp5a1 has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v1.481 ATP5A1 Sarah Leigh Classified gene: ATP5A1 as Amber List (moderate evidence)
Mitochondrial disorders v1.481 ATP5A1 Sarah Leigh Added comment: Comment on list classification: The Amber rating is based on the views of Anna de Burca (Genomics England Clinical Fellow) that the interpretation of PMID 23599390 that the boys have inherited a heterozygous variant from their father while not expressing the maternal allele due to unknown variant affecting expression.
Mitochondrial disorders v1.481 ATP5A1 Sarah Leigh Gene: atp5a1 has been classified as Amber List (Moderate Evidence).
Possible mitochondrial disorder - nuclear genes v1.2 ATP5A1 Sarah Leigh reviewed gene: ATP5A1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Respiratory ciliopathies including non-CF bronchiectasis v0.150 TTC25 Matthew Edwards reviewed gene: TTC25: Rating: GREEN; Mode of pathogenicity: None; Publications: 27486780; Phenotypes: Ciliary dyskinesia, primary, 35; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Laterality disorders and isomerism v0.41 RSPH4A Louise Daugherty changed review comment from: From GMS Respiratory Specialist Test Group webex call 18th Jan 2019 : Hannah Mitchison commented that a subset of PCD genes (DNAJB13, HYDIN, CCDC65, CCNO, DRC1, GAS8, RSPH1, RSPH3, RSPH9, RSP4A) are NOT associated with laterality disorders and should therefore be red on this panel. Hannah Mitchison to follow up with reference/confirm genes that should be downgraded to Red from Green. However, it was further noted that CCDC65 should be Amber on this panel, as other genes in this family are reliably associated with laterality defects and therefore this may reflect a lack of evidence in this case.; to: From GMS Respiratory Specialist Test Group webex call 18th Jan 2019 : Hannah Mitchison commented that a subset of PCD genes (DNAJB13, HYDIN, CCDC65, CCNO, DRC1, GAS8, RSPH1, RSPH3, RSPH9, RSPH4A) are NOT associated with laterality disorders and should therefore be red on this panel. Hannah Mitchison to follow up with reference/confirm genes that should be downgraded to Red from Green. However, it was further noted that CCDC65 should be Amber on this panel, as other genes in this family are reliably associated with laterality defects and therefore this may reflect a lack of evidence in this case.
Laterality disorders and isomerism v0.41 RSPH9 Louise Daugherty changed review comment from: From GMS Respiratory Specialist Test Group webex call 18th Jan 2019 : Hannah Mitchison commented that a subset of PCD genes (DNAJB13, HYDIN, CCDC65, CCNO, DRC1, GAS8, RSPH1, RSPH3, RSPH9, RSP4A, RSPH4A) are NOT associated with laterality disorders and should therefore be red on this panel. Hannah Mitchison to follow up with reference/confirm genes that should be downgraded to Red from Green. However, it was further noted that CCDC65 should be Amber on this panel, as other genes in this family are reliably associated with laterality defects and therefore this may reflect a lack of evidence in this case.; to: From GMS Respiratory Specialist Test Group webex call 18th Jan 2019 : Hannah Mitchison commented that a subset of PCD genes (DNAJB13, HYDIN, CCDC65, CCNO, DRC1, GAS8, RSPH1, RSPH3, RSPH9, RSPH4A) are NOT associated with laterality disorders and should therefore be red on this panel. Hannah Mitchison to follow up with reference/confirm genes that should be downgraded to Red from Green. However, it was further noted that CCDC65 should be Amber on this panel, as other genes in this family are reliably associated with laterality defects and therefore this may reflect a lack of evidence in this case.
Laterality disorders and isomerism v0.41 RSPH9 Louise Daugherty changed review comment from: From GMS Respiratory Specialist Test Group webex call 18th Jan 2019 : Hannah Mitchison commented that a subset of PCD genes (DNAJB13, HYDIN, CCDC65, CCNO, DRC1, GAS8, RSPH1, RSPH3, RSPH9, RSP4A) are NOT associated with laterality disorders and should therefore be red on this panel. Hannah Mitchison to follow up with reference/confirm genes that should be downgraded to Red from Green. However, it was further noted that CCDC65 should be Amber on this panel, as other genes in this family are reliably associated with laterality defects and therefore this may reflect a lack of evidence in this case.; to: From GMS Respiratory Specialist Test Group webex call 18th Jan 2019 : Hannah Mitchison commented that a subset of PCD genes (DNAJB13, HYDIN, CCDC65, CCNO, DRC1, GAS8, RSPH1, RSPH3, RSPH9, RSP4A, RSPH4A) are NOT associated with laterality disorders and should therefore be red on this panel. Hannah Mitchison to follow up with reference/confirm genes that should be downgraded to Red from Green. However, it was further noted that CCDC65 should be Amber on this panel, as other genes in this family are reliably associated with laterality defects and therefore this may reflect a lack of evidence in this case.
Laterality disorders and isomerism v0.41 RSPH3 Louise Daugherty changed review comment from: From GMS Respiratory Specialist Test Group webex call 18th Jan 2019 : Hannah Mitchison commented that a subset of PCD genes (DNAJB13, HYDIN, CCDC65, CCNO, DRC1, GAS8, RSPH1, RSPH3, RSPH9, RSP4A) are NOT associated with laterality disorders and should therefore be red on this panel. Hannah Mitchison to follow up with reference/confirm genes that should be downgraded to Red from Green. However, it was further noted that CCDC65 should be Amber on this panel, as other genes in this family are reliably associated with laterality defects and therefore this may reflect a lack of evidence in this case.; to: From GMS Respiratory Specialist Test Group webex call 18th Jan 2019 : Hannah Mitchison commented that a subset of PCD genes (DNAJB13, HYDIN, CCDC65, CCNO, DRC1, GAS8, RSPH1, RSPH3, RSPH9, RSPH4A) are NOT associated with laterality disorders and should therefore be red on this panel. Hannah Mitchison to follow up with reference/confirm genes that should be downgraded to Red from Green. However, it was further noted that CCDC65 should be Amber on this panel, as other genes in this family are reliably associated with laterality defects and therefore this may reflect a lack of evidence in this case.
Laterality disorders and isomerism v0.41 RSPH1 Louise Daugherty changed review comment from: From GMS Respiratory Specialist Test Group webex call 18th Jan 2019 : Hannah Mitchison commented that a subset of PCD genes (DNAJB13, HYDIN, CCDC65, CCNO, DRC1, GAS8, RSPH1, RSPH3, RSPH9, RSP4A) are NOT associated with laterality disorders and should therefore be red on this panel. Hannah Mitchison to follow up with reference/confirm genes that should be downgraded to Red from Green. However, it was further noted that CCDC65 should be Amber on this panel, as other genes in this family are reliably associated with laterality defects and therefore this may reflect a lack of evidence in this case.; to: From GMS Respiratory Specialist Test Group webex call 18th Jan 2019 : Hannah Mitchison commented that a subset of PCD genes (DNAJB13, HYDIN, CCDC65, CCNO, DRC1, GAS8, RSPH1, RSPH3, RSPH9, RSPH4A) are NOT associated with laterality disorders and should therefore be red on this panel. Hannah Mitchison to follow up with reference/confirm genes that should be downgraded to Red from Green. However, it was further noted that CCDC65 should be Amber on this panel, as other genes in this family are reliably associated with laterality defects and therefore this may reflect a lack of evidence in this case.
Laterality disorders and isomerism v0.41 GAS8 Louise Daugherty changed review comment from: From GMS Respiratory Specialist Test Group webex call 18th Jan 2019 : Hannah Mitchison commented that a subset of PCD genes (DNAJB13, HYDIN, CCDC65, CCNO, DRC1, GAS8, RSPH1, RSPH3, RSPH9, RSP4A) are NOT associated with laterality disorders and should therefore be red on this panel. Hannah Mitchison to follow up with reference/confirm genes that should be downgraded to Red from Green. However, it was further noted that CCDC65 should be Amber on this panel, as other genes in this family are reliably associated with laterality defects and therefore this may reflect a lack of evidence in this case.; to: From GMS Respiratory Specialist Test Group webex call 18th Jan 2019 : Hannah Mitchison commented that a subset of PCD genes (DNAJB13, HYDIN, CCDC65, CCNO, DRC1, GAS8, RSPH1, RSPH3, RSPH9, RSPH4A) are NOT associated with laterality disorders and should therefore be red on this panel. Hannah Mitchison to follow up with reference/confirm genes that should be downgraded to Red from Green. However, it was further noted that CCDC65 should be Amber on this panel, as other genes in this family are reliably associated with laterality defects and therefore this may reflect a lack of evidence in this case.
Laterality disorders and isomerism v0.41 DRC1 Louise Daugherty changed review comment from: From GMS Respiratory Specialist Test Group webex call 18th Jan 2019 : Hannah Mitchison commented that a subset of PCD genes (DNAJB13, HYDIN, CCDC65, CCNO, DRC1, GAS8, RSPH1, RSPH3, RSPH9, RSP4A) are NOT associated with laterality disorders and should therefore be red on this panel. Hannah Mitchison to follow up with reference/confirm genes that should be downgraded to Red from Green. However, it was further noted that CCDC65 should be Amber on this panel, as other genes in this family are reliably associated with laterality defects and therefore this may reflect a lack of evidence in this case.; to: From GMS Respiratory Specialist Test Group webex call 18th Jan 2019 : Hannah Mitchison commented that a subset of PCD genes (DNAJB13, HYDIN, CCDC65, CCNO, DRC1, GAS8, RSPH1, RSPH3, RSPH9, RSPH4A) are NOT associated with laterality disorders and should therefore be red on this panel. Hannah Mitchison to follow up with reference/confirm genes that should be downgraded to Red from Green. However, it was further noted that CCDC65 should be Amber on this panel, as other genes in this family are reliably associated with laterality defects and therefore this may reflect a lack of evidence in this case.
Laterality disorders and isomerism v0.41 CCNO Louise Daugherty changed review comment from: From GMS Respiratory Specialist Test Group webex call 18th Jan 2019 : Hannah Mitchison commented that a subset of PCD genes (DNAJB13, HYDIN, CCDC65, CCNO, DRC1, GAS8, RSPH1, RSPH3, RSPH9, RSP4A) are NOT associated with laterality disorders and should therefore be red on this panel. Hannah Mitchison to follow up with reference/confirm genes that should be downgraded to Red from Green. However, it was further noted that CCDC65 should be Amber on this panel, as other genes in this family are reliably associated with laterality defects and therefore this may reflect a lack of evidence in this case.; to: From GMS Respiratory Specialist Test Group webex call 18th Jan 2019 : Hannah Mitchison commented that a subset of PCD genes (DNAJB13, HYDIN, CCDC65, CCNO, DRC1, GAS8, RSPH1, RSPH3, RSPH9, RSPH4A) are NOT associated with laterality disorders and should therefore be red on this panel. Hannah Mitchison to follow up with reference/confirm genes that should be downgraded to Red from Green. However, it was further noted that CCDC65 should be Amber on this panel, as other genes in this family are reliably associated with laterality defects and therefore this may reflect a lack of evidence in this case.
Laterality disorders and isomerism v0.41 CCDC65 Louise Daugherty changed review comment from: From GMS Respiratory Specialist Test Group webex call 18th Jan 2019 : Hannah Mitchison commented that a subset of PCD genes (DNAJB13, HYDIN, CCDC65, CCNO, DRC1, GAS8, RSPH1, RSPH3, RSPH9, RSP4A) are NOT associated with laterality disorders and should therefore be red on this panel. Hannah Mitchison to follow up with reference/confirm genes that should be downgraded to Red from Green. However, it was further noted that CCDC65 should be Amber on this panel, as other genes in this family are reliably associated with laterality defects and therefore this may reflect a lack of evidence in this case.; to: From GMS Respiratory Specialist Test Group webex call 18th Jan 2019 : Hannah Mitchison commented that a subset of PCD genes (DNAJB13, HYDIN, CCDC65, CCNO, DRC1, GAS8, RSPH1, RSPH3, RSPH9, RSPH4A) are NOT associated with laterality disorders and should therefore be red on this panel. Hannah Mitchison to follow up with reference/confirm genes that should be downgraded to Red from Green. However, it was further noted that CCDC65 should be Amber on this panel, as other genes in this family are reliably associated with laterality defects and therefore this may reflect a lack of evidence in this case.
Laterality disorders and isomerism v0.41 HYDIN Louise Daugherty changed review comment from: FFrom GMS Respiratory Specialist Test Group webex call 18th Jan 2019 : Hannah Mitchison commented that a subset of PCD genes (DNAJB13, HYDIN, CCDC65, CCNO, DRC1, GAS8, RSPH1, RSPH3, RSPH9, RSP4A) are NOT associated with laterality disorders and should therefore be red on this panel. Hannah Mitchison to follow up with reference/confirm genes that should be downgraded to Red from Green. However, it was further noted that CCDC65 should be Amber on this panel, as other genes in this family are reliably associated with laterality defects and therefore this may reflect a lack of evidence in this case.; to: FFrom GMS Respiratory Specialist Test Group webex call 18th Jan 2019 : Hannah Mitchison commented that a subset of PCD genes (DNAJB13, HYDIN, CCDC65, CCNO, DRC1, GAS8, RSPH1, RSPH3, RSPH9, RSPH4A) are NOT associated with laterality disorders and should therefore be red on this panel. Hannah Mitchison to follow up with reference/confirm genes that should be downgraded to Red from Green. However, it was further noted that CCDC65 should be Amber on this panel, as other genes in this family are reliably associated with laterality defects and therefore this may reflect a lack of evidence in this case.
Laterality disorders and isomerism v0.41 DNAJB13 Louise Daugherty changed review comment from: From GMS Respiratory Specialist Test Group webex call 18th Jan 2019 : Hannah Mitchison commented that a subset of PCD genes (DNAJB13, HYDIN, CCDC65, CCNO, DRC1, GAS8, RSPH1, RSPH3, RSPH9, RSP4A) are NOT associated with laterality disorders and should therefore be red on this panel. Hannah Mitchison to follow up with reference/confirm genes that should be downgraded to Red from Green. However, it was further noted that CCDC65 should be Amber on this panel, as other genes in this family are reliably associated with laterality defects and therefore this may reflect a lack of evidence in this case.; to: From GMS Respiratory Specialist Test Group webex call 18th Jan 2019 : Hannah Mitchison commented that a subset of PCD genes (DNAJB13, HYDIN, CCDC65, CCNO, DRC1, GAS8, RSPH1, RSPH3, RSPH9, RSPH4A) are NOT associated with laterality disorders and should therefore be red on this panel. Hannah Mitchison to follow up with reference/confirm genes that should be downgraded to Red from Green. However, it was further noted that CCDC65 should be Amber on this panel, as other genes in this family are reliably associated with laterality defects and therefore this may reflect a lack of evidence in this case.
Surfactant deficiency v0.25 SFTPC Louise Daugherty commented on gene: SFTPC: From GMS Respiratory Specialist Test Group webex call 18th Jan 2019: it was agreed there was evidence to rate this gene Green on this panel, test group would further provide MOI and Phenotypes and if possible add PMID to support rating
Surfactant deficiency v0.25 SFTPC Louise Daugherty commented on gene: SFTPC: Added MOI, Phenotypes and Publications as suggested by expert review Matthew Edwards (Clinical Genetics & Genomics Lab, Royal Brompton & Harefield NHS Trust)
Surfactant deficiency v0.25 SFTPC Louise Daugherty Phenotypes for gene: SFTPC were changed from to Surfactant metabolism dysfunction, pulmonary 2, 610913
Surfactant deficiency v0.24 SFTPC Louise Daugherty Publications for gene: SFTPC were set to
Surfactant deficiency v0.23 SFTPC Louise Daugherty Mode of inheritance for gene: SFTPC was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Surfactant deficiency v0.22 SFTPB Louise Daugherty commented on gene: SFTPB: From GMS Respiratory Specialist Test Group webex call 18th Jan 2019: it was agreed there was evidence to rate this gene Green on this panel, test group would further provide MOI and Phenotypes and if possible add PMID to support rating.
Surfactant deficiency v0.22 SFTPB Louise Daugherty changed review comment from: Added MOI, Phenotypes and Publications as suggested by expert review Matthew Edwards (Clinical Genetics & Genomics Lab, Royal Brompton & Harefield NHS Trust); to: Added MOI, Phenotypes and Publications as suggested by expert review Matthew Edwards (Clinical Genetics & Genomics Lab, Royal Brompton & Harefield NHS Trust)
Surfactant deficiency v0.22 SFTPB Louise Daugherty commented on gene: SFTPB: Added MOI, Phenotypes and Publications as suggested by expert review Matthew Edwards (Clinical Genetics & Genomics Lab, Royal Brompton & Harefield NHS Trust)
Surfactant deficiency v0.22 SFTPB Louise Daugherty Phenotypes for gene: SFTPB were changed from to Surfactant metabolism dysfunction, pulmonary 1, 265120
Surfactant deficiency v0.21 SFTPB Louise Daugherty Publications for gene: SFTPB were set to
Surfactant deficiency v0.20 SFTPB Louise Daugherty Mode of inheritance for gene: SFTPB was changed from to BIALLELIC, autosomal or pseudoautosomal
Surfactant deficiency v0.19 NKX2-1 Louise Daugherty commented on gene: NKX2-1: Added MOI, Phenotypes and Publications as suggested by expert review Matthew Edwards (Clinical Genetics & Genomics Lab, Royal Brompton & Harefield NHS Trust)
Surfactant deficiency v0.19 NKX2-1 Louise Daugherty Phenotypes for gene: NKX2-1 were changed from to Neuroendocrine cell hyperplasia of infancy; Choreoathetosis, hypothyroidism, and neonatal respiratory distress, 610978
Surfactant deficiency v0.18 NKX2-1 Louise Daugherty Publications for gene: NKX2-1 were set to
Surfactant deficiency v0.17 ABCA3 Louise Daugherty commented on gene: ABCA3: From GMS Respiratory Specialist Test Group webex call 18th Jan 2019: it was agreed there was evidence to rate this gene Green on this panel, test group would further provide MOI and Phenotypes and if possible add PMID to support rating.
Surfactant deficiency v0.17 ABCA3 Louise Daugherty commented on gene: ABCA3: Added MOI, Phenotypes and Publications as suggested by expert review Matthew Edwards (Clinical Genetics & Genomics Lab, Royal Brompton & Harefield NHS Trust)
Surfactant deficiency v0.17 ABCA3 Louise Daugherty Deleted their comment
Surfactant deficiency v0.17 ABCA3 Louise Daugherty Deleted their comment
Surfactant deficiency v0.17 ABCA3 Louise Daugherty Deleted their comment
Surfactant deficiency v0.17 NKX2-1 Louise Daugherty Deleted their comment
Surfactant deficiency v0.17 NKX2-1 Louise Daugherty Added comment: Comment on mode of inheritance: added MOI from expert review Matthew Edwards (Clinical Genetics & Genomics Lab, Royal Brompton & Harefield NHS Trust)
Surfactant deficiency v0.17 NKX2-1 Louise Daugherty Mode of inheritance for gene: NKX2-1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Surfactant deficiency v0.16 ABCA3 Louise Daugherty Publications for gene: ABCA3 were set to 15044640
Surfactant deficiency v0.15 ABCA3 Louise Daugherty edited their review of gene: ABCA3: Changed publications: 17719949
Surfactant deficiency v0.15 ABCA3 Louise Daugherty Added comment: Comment on phenotypes: added OMIM phenotype as recommended by expert reviewer
Surfactant deficiency v0.15 ABCA3 Louise Daugherty Phenotypes for gene: ABCA3 were changed from to Surfactant metabolism dysfunction, pulmonary 3, 610921
Surfactant deficiency v0.14 ABCA3 Louise Daugherty Added comment: Comment on publications: added PMID from expert review Matthew Edwards (Clinical Genetics & Genomics Lab, Royal Brompton & Harefield NHS Trust) to support gene and rating on this panel
Surfactant deficiency v0.14 ABCA3 Louise Daugherty Publications for gene: ABCA3 were set to
Surfactant deficiency v0.13 ABCA3 Louise Daugherty Added comment: Comment on mode of inheritance: added MOI from expert review Matthew Edwards (Clinical Genetics & Genomics Lab, Royal Brompton & Harefield NHS Trust)
Surfactant deficiency v0.13 ABCA3 Louise Daugherty Mode of inheritance for gene: ABCA3 was changed from to BIALLELIC, autosomal or pseudoautosomal
Surfactant deficiency v0.12 SFTPA2 Louise Daugherty Added comment: Comment on publications: added publications suggested by external review Matthew Edwards
Surfactant deficiency v0.12 SFTPA2 Louise Daugherty Publications for gene: SFTPA2 were set to
Clefting v1.44 ALX1 Catherine Snow Classified gene: ALX1 as Amber List (moderate evidence)
Clefting v1.44 ALX1 Catherine Snow Added comment: Comment on list classification: Changed to Amber based on Eleanor Williams review.
Clefting v1.44 ALX1 Catherine Snow Gene: alx1 has been classified as Amber List (Moderate Evidence).
Clefting v1.43 EIF4A3 Catherine Snow reviewed gene: EIF4A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 10594883, 29922329, 29112243; Phenotypes: Robin sequence with cleft mandible and limb anomalies, 268305, Richieri-Costa-Pereira syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Pulmonary arterial hypertension v1.48 Louise Daugherty List of related panels changed from PAH to PAH; R188
Hereditary haemorrhagic telangiectasia v1.51 Louise Daugherty List of related panels changed from Familial and multiple pulmonary arteriovenous malformations to Familial and multiple pulmonary arteriovenous malformations; R186
Clefting v1.43 BMP2 Catherine Snow Phenotypes for gene: BMP2 were changed from Cleft palate to Cleft palate; Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies, 617877
Clefting v1.42 BMP2 Catherine Snow Publications for gene: BMP2 were set to
Clefting v1.41 BMP2 Catherine Snow Mode of inheritance for gene: BMP2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Clefting v1.40 BMP2 Catherine Snow Classified gene: BMP2 as Green List (high evidence)
Clefting v1.40 BMP2 Catherine Snow Gene: bmp2 has been classified as Green List (High Evidence).
Clefting v1.39 BMP2 Catherine Snow reviewed gene: BMP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 21671386, 29198724; Phenotypes: Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies, 617877; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Surfactant deficiency v0.11 CSF2RB Matthew Edwards reviewed gene: CSF2RB: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Surfactant deficiency v0.11 SFTPA2 Matthew Edwards reviewed gene: SFTPA2: Rating: AMBER; Mode of pathogenicity: None; Publications: 19100526, 26568241; Phenotypes: Pulmonary fibrosis, idiopathic (OMIM: 178500); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Surfactant deficiency v0.11 SFTPC Matthew Edwards reviewed gene: SFTPC: Rating: GREEN; Mode of pathogenicity: None; Publications: 11207353, 19443464; Phenotypes: Surfactant metabolism dysfunction, pulmonary, 2 (OMIM: 610913); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Surfactant deficiency v0.11 SFTPB Matthew Edwards reviewed gene: SFTPB: Rating: GREEN; Mode of pathogenicity: None; Publications: 8163685, 12501227, 10712351; Phenotypes: Surfactant metabolism dysfunction, pulmonary, 1 (OMIM: 265120); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Undiagnosed metabolic disorders v1.246 PRPS1 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.246 PRPS1 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.246 PRPS1 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.246 PRPS1 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.246 PRPS1 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.246 PRPS1 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.246 PRPS1 Sarah Leigh Deleted their comment
Surfactant deficiency v0.11 NKX2-1 Matthew Edwards changed review comment from: On Royal Brompton Childhood interstitial lung disease (surfactant deficiency) panel, andl pathogenic variants reported . Multiple reports in literature and ClinVar. Strong evidence for association.; to: On Royal Brompton Childhood interstitial lung disease (surfactant deficiency) panel, and pathogenic variants reported . Multiple reports in literature and ClinVar. Strong evidence for association.
Surfactant deficiency v0.11 NKX2-1 Matthew Edwards reviewed gene: NKX2-1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23787483, 15289765; Phenotypes: Neuroendocrine cell hyperplasia of infancy, Choreoathetosis, hypothyroidism, and neonatal respiratory distress (OMIM 610978); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Inborn errors of metabolism v1.242 POR Sarah Leigh Publications for gene: POR were set to 27604308
Undiagnosed metabolic disorders v1.246 POR Sarah Leigh Publications for gene: POR were set to 27604308
Undiagnosed metabolic disorders v1.245 POR Sarah Leigh Classified gene: POR as Green List (high evidence)
Undiagnosed metabolic disorders v1.245 POR Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 10 variants associated with Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis 201750 and 6 variants associated with Disordered steroidogenesis due to cytochrome P450 oxidoreductase 613571.
Undiagnosed metabolic disorders v1.245 POR Sarah Leigh Gene: por has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.241 POR Sarah Leigh Classified gene: POR as Green List (high evidence)
Inborn errors of metabolism v1.241 POR Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 10 variants associated with Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis 201750 and 6 variants associated with Disordered steroidogenesis due to cytochrome P450 oxidoreductase 613571.
Inborn errors of metabolism v1.241 POR Sarah Leigh Gene: por has been classified as Green List (High Evidence).
Mitochondrial disorders v1.480 SPATA5 Sarah Leigh Publications for gene: SPATA5 were set to PMID: 27246907; 29343804; 26299366
Mitochondrial disorders v1.479 SPATA5 Sarah Leigh Classified gene: SPATA5 as Amber List (moderate evidence)
Mitochondrial disorders v1.479 SPATA5 Sarah Leigh Added comment: Comment on list classification: This gene is being rated as amber as it has not been reviewed as green by the GMS Mitochondrial specialist test group.
Mitochondrial disorders v1.479 SPATA5 Sarah Leigh Gene: spata5 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v1.256 SPATA5 Sarah Leigh Publications for gene: SPATA5 were set to PMID: 27246907; 29343804; 26299366
Genetic epilepsy syndromes v1.255 SPATA5 Sarah Leigh Classified gene: SPATA5 as Green List (high evidence)
Genetic epilepsy syndromes v1.255 SPATA5 Sarah Leigh Added comment: Comment on list classification: Based on review from Rachel Jones (GSTT): Tanaka et al PMID: 26299366 identified "14 individuals [from 10 families] with microcephaly, developmental delay, intellectual disability, hypotonia, spasticity, seizures, sensorineural hearing loss, cortical visual impairment, and rare autosomal-recessive predicted pathogenic variants" in SPATA5 Puussep et al PMID: 29343804 describes 5 further patients "with psychomotor developmental delay, microcephaly, epilepsy and hearing impairment, who were thought clinically to have a mitochondrial disease with subsequent whole-exome sequencing analysis detecting compound heterozygous variants in the SPATA5 gene" Szczaluba et al PMID: 28293831 describes a family where a sibling has isolated sensorineural hearing loss and the same two pathogenic SPATA5 variants as her more typically affected sister. In addition, typically affected individuals may present as congenital SNHL on newborn hearing screen prior to onset of seizures, microcephaly and intellectual disability.
Genetic epilepsy syndromes v1.255 SPATA5 Sarah Leigh Gene: spata5 has been classified as Green List (High Evidence).
Surfactant deficiency v0.11 ABCA3 Matthew Edwards reviewed gene: ABCA3: Rating: GREEN; Mode of pathogenicity: None; Publications: 15044640; Phenotypes: Surfactant metabolism dysfunction, pulmonary, 3 (OMIM: 610921); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Familial pulmonary fibrosis v1.6 PARN Louise Daugherty Added comment: Comment on publications: added new PMID as advised by external reivew
Familial pulmonary fibrosis v1.6 PARN Louise Daugherty Publications for gene: PARN were set to 25848748
Molecular autopsy v0.99 PITRM1 Sarah Leigh reviewed gene: PITRM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29764912, 26697887, 29383861; Phenotypes: ; Mode of inheritance: None
Possible mitochondrial disorder - nuclear genes v1.2 PITRM1 Sarah Leigh commented on gene: PITRM1: Based on publications pmids 29764912; 26697887; 29383861
Mitochondrial disorders v1.478 PITRM1 Sarah Leigh edited their review of gene: PITRM1: Added comment: Based on publications pmids 29764912; 26697887; 29383861; Changed rating: GREEN
Mitochondrial disorders v1.478 PITRM1 Sarah Leigh Classified gene: PITRM1 as Amber List (moderate evidence)
Mitochondrial disorders v1.478 PITRM1 Sarah Leigh Added comment: Comment on list classification: This gene is being demoted to amber as it has not been reviewed as green by the GMS Mitochondrial specialist test group.
Mitochondrial disorders v1.478 PITRM1 Sarah Leigh Gene: pitrm1 has been classified as Amber List (Moderate Evidence).
Inborn errors of metabolism v1.240 PITRM1 Sarah Leigh Classified gene: PITRM1 as Amber List (moderate evidence)
Inborn errors of metabolism v1.240 PITRM1 Sarah Leigh Added comment: Comment on list classification: This gene is being demoted to amber as it has not been reviewed as green by the GMS Mitochondrial specialist test group.
Inborn errors of metabolism v1.240 PITRM1 Sarah Leigh Gene: pitrm1 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v1.72 UFC1 Louise Daugherty Added comment: Comment on publications: review from Geoff Woods: 5 families reported in PMID 30552426 and 29868776
Severe microcephaly v1.72 UFC1 Louise Daugherty Publications for gene: UFC1 were set to 26917597
Inborn errors of metabolism v1.239 POR Sarah Leigh Phenotypes for gene: POR were changed from Antley-Bixler syndrome with disordered steroidogenesis; Unexplained skeletal dysplasia; Disorders of sex development; Craniosynostosis syndromes phenotypes to Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis 201750; Disordered steroidogenesis due to cytochrome P450 oxidoreductase 613571
Undiagnosed metabolic disorders v1.244 POR Sarah Leigh Phenotypes for gene: POR were changed from Antley-Bixler syndrome with disordered steroidogenesis; Craniosynostosis syndromes phenotypes; Disorders of sex development; Unexplained skeletal dysplasia to Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis 201750; Disordered steroidogenesis due to cytochrome P450 oxidoreductase 613571
Undiagnosed metabolic disorders v1.243 POR Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.243 POR Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.243 POR Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.243 POR Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.243 POR Sarah Leigh Deleted their comment
Severe microcephaly v1.71 ZNHIT3 Louise Daugherty Publications for gene: ZNHIT3 were set to
Inborn errors of metabolism v1.238 PNP Sarah Leigh Publications for gene: PNP were set to 27604308; 3029074; 1384322; 9067751; 8931706; 9737781; 11453975
Severe microcephaly v1.70 PCLO Louise Daugherty Publications for gene: PCLO were set to
Inborn errors of metabolism v1.238 PNP Sarah Leigh Publications for gene: PNP were set to 27604308
Inborn errors of metabolism v1.237 PNP Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.243 PNP Sarah Leigh Publications for gene: PNP were set to 27604308
Severe microcephaly v1.69 UBA5 Louise Daugherty Publications for gene: UBA5 were set to
Inborn errors of metabolism v1.237 PNP Sarah Leigh Classified gene: PNP as Green List (high evidence)
Inborn errors of metabolism v1.237 PNP Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 10 variants reported.
Inborn errors of metabolism v1.237 PNP Sarah Leigh Gene: pnp has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.237 PNP Sarah Leigh Classified gene: PNP as Green List (high evidence)
Inborn errors of metabolism v1.237 PNP Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 10 variants reported.
Inborn errors of metabolism v1.237 PNP Sarah Leigh Gene: pnp has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.242 PNP Sarah Leigh Classified gene: PNP as Green List (high evidence)
Undiagnosed metabolic disorders v1.242 PNP Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 10 variants reported.
Undiagnosed metabolic disorders v1.242 PNP Sarah Leigh Gene: pnp has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.241 PNP Sarah Leigh Added comment: Comment on phenotypes: Purine nucleoside phosphorylase deficiency (Disorders of purine metabolism);SCID
Undiagnosed metabolic disorders v1.241 PNP Sarah Leigh Phenotypes for gene: PNP were changed from Purine nucleoside phosphorylase deficiency (Disorders of purine metabolism); SCID to Immunodeficiency due to purine nucleoside phosphorylase deficiency 613179
Inborn errors of metabolism v1.236 PNP Sarah Leigh Added comment: Comment on phenotypes: SCID;Purine nucleoside phosphorylase deficiency (Disorders of purine metabolism)
Inborn errors of metabolism v1.236 PNP Sarah Leigh Phenotypes for gene: PNP were changed from SCID; Purine nucleoside phosphorylase deficiency (Disorders of purine metabolism) to Immunodeficiency due to purine nucleoside phosphorylase deficiency 613179
Undiagnosed metabolic disorders v1.240 PNP Sarah Leigh Deleted their comment
Inborn errors of metabolism v1.235 PINK1 Sarah Leigh Classified gene: PINK1 as Green List (high evidence)
Inborn errors of metabolism v1.235 PINK1 Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 12 variants were reported.
Inborn errors of metabolism v1.235 PINK1 Sarah Leigh Gene: pink1 has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.240 PINK1 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.240 PINK1 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.240 PINK1 Sarah Leigh Classified gene: PINK1 as Green List (high evidence)
Undiagnosed metabolic disorders v1.240 PINK1 Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 12 variants were reported.
Undiagnosed metabolic disorders v1.240 PINK1 Sarah Leigh Gene: pink1 has been classified as Green List (High Evidence).
Severe microcephaly v1.68 UFC1 Louise Daugherty Publications for gene: UFC1 were set to
Mitochondrial disorders v1.477 SPATA5 Rachel Jones gene: SPATA5 was added
gene: SPATA5 was added to Mitochondrial disorders. Sources: Literature
Mode of inheritance for gene: SPATA5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPATA5 were set to PMID: 27246907; 29343804; 26299366
Phenotypes for gene: SPATA5 were set to Epilepsy, hearing loss, and mental retardation syndrome 616577
Penetrance for gene: SPATA5 were set to Complete
Review for gene: SPATA5 was set to GREEN
Added comment: Greater than 15 families have been identified in multiple publications showing that patients with SPATA5 biallelic variants present with intellectual disability, epilepsy, microcephaly and hearing loss, as well as cortical blindness, spasticity and feeding problems; and prior to the gene being discovered to cause the phenotype in these families patients were often thought to have a mitochondrial disorder.

As per Puusepp et al (PMID: 29343804) functional studies were performed on rat cortical neurons. "SPATA5-deficient neurons had a significant imbalance in the mitochondrial fusion-fission rate, impaired energy production and short axons. In conclusion, SPATA5 protein has an important role in mitochondrial dynamics and axonal growth. Biallelic variants in the SPATA5 gene can affect mitochondria in cortical neurons and should be considered in patients with a neurodegenerative disorder and/or with clinical presentation resembling a mitochondrial disorder."
Sources: Literature
Inborn errors of metabolism v1.234 PINK1 Sarah Leigh Added comment: Comment on publications: Many more publications
Inborn errors of metabolism v1.234 PINK1 Sarah Leigh Publications for gene: PINK1 were set to 27604308
Undiagnosed metabolic disorders v1.239 PINK1 Sarah Leigh Added comment: Comment on publications: Many more publications
Undiagnosed metabolic disorders v1.239 PINK1 Sarah Leigh Publications for gene: PINK1 were set to 27604308
Inborn errors of metabolism v1.233 PINK1 Sarah Leigh Added comment: Comment on phenotypes: Mitochondrial respiratory chain disorders (caused by nuclear variants only)
Inborn errors of metabolism v1.233 PINK1 Sarah Leigh Phenotypes for gene: PINK1 were changed from Early onset dystonia; Parkinson disease 6, early onset (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Parkinson Disease and Complex Parkinsonism to Parkinson disease 6, early onset 605909
Undiagnosed metabolic disorders v1.238 PINK1 Sarah Leigh Added comment: Comment on phenotypes: Mitochondrial respiratory chain disorders (caused by nuclear variants only)
Undiagnosed metabolic disorders v1.238 PINK1 Sarah Leigh Phenotypes for gene: PINK1 were changed from Parkinson disease 6, early onset (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Early onset dystonia; Parkinson Disease and Complex Parkinsonism to Parkinson disease 6, early onset 605909
Undiagnosed metabolic disorders v1.237 PINK1 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.237 PINK1 Sarah Leigh Deleted their comment
Genetic epilepsy syndromes v1.254 SPATA5 Rachel Jones gene: SPATA5 was added
gene: SPATA5 was added to Genetic epilepsy syndromes. Sources: Other
Mode of inheritance for gene: SPATA5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPATA5 were set to PMID: 27246907; 29343804; 26299366
Phenotypes for gene: SPATA5 were set to Epilepsy, hearing loss, and mental retardation syndrome 616577
Penetrance for gene: SPATA5 were set to Incomplete
Review for gene: SPATA5 was set to GREEN
Added comment: Greater than 15 families have been identified in multiple publications showing that patients with SPATA5 biallelic variants present with intellectual disability, epilepsy, microcephaly and hearing loss. May present as epileptic encephalopathy/epilepsy in the first year of life prior to onset of obvious developmental delay.
Sources: Other
Inborn errors of metabolism v1.232 PIGM Sarah Leigh Classified gene: PIGM as Amber List (moderate evidence)
Inborn errors of metabolism v1.232 PIGM Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM and as possible Gen2Phen gene. At least 1 variant was reported in 2 unrelated families (PMID 16767100), together with supportive functional studies (PMID 17442906 & 25293775).
Inborn errors of metabolism v1.232 PIGM Sarah Leigh Gene: pigm has been classified as Amber List (Moderate Evidence).
Inborn errors of metabolism v1.231 PIGM Sarah Leigh Deleted their comment
Inborn errors of metabolism v1.231 PIGM Sarah Leigh Classified gene: PIGM as Amber List (moderate evidence)
Inborn errors of metabolism v1.231 PIGM Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM and as possible Gen2Phen gene. At least 1 variant was reported in 2 unrelated families (PMID 16767100), together with supportive functional studies (PMID 17442906 & 25293775).
Inborn errors of metabolism v1.231 PIGM Sarah Leigh Gene: pigm has been classified as Amber List (Moderate Evidence).
Inborn errors of metabolism v1.231 PIGM Sarah Leigh Classified gene: PIGM as Amber List (moderate evidence)
Inborn errors of metabolism v1.231 PIGM Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM and as possible Gen2Phen gene. At least 1 variant was reported in 2 unrelated families (PMID 16767100), together with supportive functional studies (PMID 17442906 & 25293775).
Inborn errors of metabolism v1.231 PIGM Sarah Leigh Gene: pigm has been classified as Amber List (Moderate Evidence).
Undiagnosed metabolic disorders v1.237 PIGM Sarah Leigh Classified gene: PIGM as Amber List (moderate evidence)
Undiagnosed metabolic disorders v1.237 PIGM Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as possible Gen2Phen gene. At least 1 variant was reported in 2 unrelated families (PMID 16767100), together with supportive functional studies (PMID 17442906 & 25293775).
Undiagnosed metabolic disorders v1.237 PIGM Sarah Leigh Gene: pigm has been classified as Amber List (Moderate Evidence).
Clefting v1.39 Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; Component Of Super Panel
Inborn errors of metabolism v1.230 PIGM Sarah Leigh Publications for gene: PIGM were set to 27604308; 16767100; 25293775; 17442906
Inborn errors of metabolism v1.230 PIGM Sarah Leigh Publications for gene: PIGM were set to 27604308; 16767100; 25293775; 17442906; 25293775
Inborn errors of metabolism v1.229 PIGM Sarah Leigh Publications for gene: PIGM were set to 27604308; 16767100; 25293775
Undiagnosed metabolic disorders v1.236 PIGM Sarah Leigh Publications for gene: PIGM were set to 27604308; 25293775; 16767100
Paediatric disorders v3.883 Ellen McDonagh Changed child panels to: Intellectual disability; Inborn errors of metabolism; Skeletal dysplasia; DDG2P; Limb disorders; Clefting; Paediatric disorders - additional genes; Skeletal ciliopathies; Ophthalmological ciliopathies; Neurological ciliopathies; Renal ciliopathies
Inborn errors of metabolism v1.228 PIGM Sarah Leigh Added comment: Comment on phenotypes: Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation;Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency
Inborn errors of metabolism v1.228 PIGM Sarah Leigh Phenotypes for gene: PIGM were changed from Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation; Glycosylphosphatidylinositol deficiency, 610293; Glycosylphosphatidylinositol deficiency 610293; Phosphatidylinositolglycan, class M deficiency (Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation); Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency to Glycosylphosphatidylinositol deficiency 610293
Undiagnosed metabolic disorders v1.235 PIGM Sarah Leigh Added comment: Comment on phenotypes: Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation;Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency
Undiagnosed metabolic disorders v1.235 PIGM Sarah Leigh Phenotypes for gene: PIGM were changed from Phosphatidylinositolglycan, class M deficiency (Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation); Glycosylphosphatidylinositol deficiency 610293 to Glycosylphosphatidylinositol deficiency 610293
Inborn errors of metabolism v1.227 PHGDH Sarah Leigh Publications for gene: PHGDH were set to 27604308; 24816252
Undiagnosed metabolic disorders v1.234 PHGDH Sarah Leigh Publications for gene: PHGDH were set to 27604308; 24816252
Inborn errors of metabolism v1.226 PHGDH Sarah Leigh Classified gene: PHGDH as Green List (high evidence)
Inborn errors of metabolism v1.226 PHGDH Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene for both phenotypes. At least 6 variants reported in 6 unrelated cases of Phosphoglycerate dehydrogenase deficiency 601815 and 4 variants reported in 4 unrelated cases of Neu-Laxova syndrome 1 256520.
Inborn errors of metabolism v1.226 PHGDH Sarah Leigh Gene: phgdh has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.233 PHGDH Sarah Leigh Classified gene: PHGDH as Green List (high evidence)
Undiagnosed metabolic disorders v1.233 PHGDH Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene for both phenotypes. At least 6 variants reported in 6 unrelated cases of Phosphoglycerate dehydrogenase deficiency 601815 and 4 variants reported in 4 unrelated cases of Neu-Laxova syndrome 1 256520.
Undiagnosed metabolic disorders v1.233 PHGDH Sarah Leigh Gene: phgdh has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.225 PHGDH Sarah Leigh Added comment: Comment on phenotypes: Phosphoglycerate dehydrogenase deficiency (Disorders of serine, glycine or glycerate metabolism)
Inborn errors of metabolism v1.225 PHGDH Sarah Leigh Phenotypes for gene: PHGDH were changed from Neu-Laxova syndrome 1 256520; Phosphoglycerate dehydrogenase deficiency 601815 to Neu-Laxova syndrome 1 256520; Phosphoglycerate dehydrogenase deficiency 601815
Inborn errors of metabolism v1.225 PHGDH Sarah Leigh Added comment: Comment on phenotypes: Phosphoglycerate dehydrogenase deficiency (Disorders of serine, glycine or glycerate metabolism)
Inborn errors of metabolism v1.225 PHGDH Sarah Leigh Phenotypes for gene: PHGDH were changed from Phosphoglycerate dehydrogenase deficiency (Disorders of serine, glycine or glycerate metabolism); Unexplained skeletal dysplasia; Intellectual disability to Neu-Laxova syndrome 1 256520; Phosphoglycerate dehydrogenase deficiency 601815
Undiagnosed metabolic disorders v1.232 PHGDH Sarah Leigh Added comment: Comment on phenotypes: Phosphoglycerate dehydrogenase deficiency (Disorders of serine, glycine or glycerate metabolism)
Undiagnosed metabolic disorders v1.232 PHGDH Sarah Leigh Phenotypes for gene: PHGDH were changed from Phosphoglycerate dehydrogenase deficiency (Disorders of serine, glycine or glycerate metabolism); Intellectual disability; Unexplained skeletal dysplasia to Neu-Laxova syndrome 1 256520; Phosphoglycerate dehydrogenase deficiency 601815
Undiagnosed metabolic disorders v1.231 PHGDH Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.231 PHGDH Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.231 PHGDH Sarah Leigh Deleted their comment
Inborn errors of metabolism v1.224 PEPD Sarah Leigh Publications for gene: PEPD were set to 27604308; 2365824; 2365824; 8198124; 15309682; 16470701
Inborn errors of metabolism v1.223 PEPD Sarah Leigh Publications for gene: PEPD were set to 27604308; 2365824; 2365824; 8198124; 15309682; 16470701
Inborn errors of metabolism v1.223 PEPD Sarah Leigh Publications for gene: PEPD were set to 27604308
Undiagnosed metabolic disorders v1.231 PEPD Sarah Leigh Publications for gene: PEPD were set to 27604308
Inborn errors of metabolism v1.222 PEPD Sarah Leigh Classified gene: PEPD as Green List (high evidence)
Inborn errors of metabolism v1.222 PEPD Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 11 variants reported.
Inborn errors of metabolism v1.222 PEPD Sarah Leigh Gene: pepd has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.222 PEPD Sarah Leigh Classified gene: PEPD as Green List (high evidence)
Inborn errors of metabolism v1.222 PEPD Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 11 variants reported.
Inborn errors of metabolism v1.222 PEPD Sarah Leigh Gene: pepd has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.230 PEPD Sarah Leigh Classified gene: PEPD as Green List (high evidence)
Undiagnosed metabolic disorders v1.230 PEPD Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 11 variants reported.
Undiagnosed metabolic disorders v1.230 PEPD Sarah Leigh Gene: pepd has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.229 PEPD Sarah Leigh Added comment: Comment on phenotypes: Prolidase deficiency (Other disorders of peptide metabolism)
Undiagnosed metabolic disorders v1.229 PEPD Sarah Leigh Phenotypes for gene: PEPD were changed from Prolidase deficiency (Other disorders of peptide metabolism); Intellectual disability to Prolidase deficiency 170100
Inborn errors of metabolism v1.221 PEPD Sarah Leigh Added comment: Comment on phenotypes: Prolidase deficiency (Other disorders of peptide metabolism)
Inborn errors of metabolism v1.221 PEPD Sarah Leigh Phenotypes for gene: PEPD were changed from Intellectual disability; Prolidase deficiency (Other disorders of peptide metabolism) to Prolidase deficiency 170100
Undiagnosed metabolic disorders v1.228 PEPD Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.228 PDPR Sarah Leigh Classified gene: PDPR as Red List (low evidence)
Undiagnosed metabolic disorders v1.228 PDPR Sarah Leigh Added comment: Comment on list classification: Not associated with a phenotype in OMIM or in Gen2Phen. At least 1 variant reported in a case of global developmental delay, typical Joubert syndrome, according to PMID 25558065.
Undiagnosed metabolic disorders v1.228 PDPR Sarah Leigh Gene: pdpr has been classified as Red List (Low Evidence).
Inborn errors of metabolism v1.220 PDPR Sarah Leigh changed review comment from: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 1 variant reported in a case of global developmental delay, typical Joubert syndrome, according to PMID 25558065.; to: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Not associated with a phenotype in OMIM or in Gen2Phen. At least 1 variant reported in a case of global developmental delay, typical Joubert syndrome, according to PMID 25558065.
Inborn errors of metabolism v1.220 PDPR Sarah Leigh Mode of inheritance for gene: PDPR was changed from BIALLELIC, autosomal or pseudoautosomal to Unknown
Inborn errors of metabolism v1.219 PDPR Sarah Leigh Classified gene: PDPR as Red List (low evidence)
Inborn errors of metabolism v1.219 PDPR Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 1 variant reported in a case of global developmental delay, typical Joubert syndrome, according to PMID 25558065.
Inborn errors of metabolism v1.219 PDPR Sarah Leigh Gene: pdpr has been classified as Red List (Low Evidence).
Inborn errors of metabolism v1.218 PDPR Sarah Leigh Added comment: Comment on phenotypes: Global developmental delay, typical Joubert syndrome, according to PMID 25558065.
Inborn errors of metabolism v1.218 PDPR Sarah Leigh Phenotypes for gene: PDPR were changed from Pyruvate dehydrogenase phosphatase deficiency (Disorders of pyruvate metabolism) to Pyruvate dehydrogenase phosphatase deficiency (Disorders of pyruvate metabolism)
Inborn errors of metabolism v1.217 PDPR Sarah Leigh Publications for gene: PDPR were set to 27604308; 25558065
Inborn errors of metabolism v1.216 PDPR Sarah Leigh Publications for gene: PDPR were set to 27604308; 25558065
Inborn errors of metabolism v1.215 PCSK9 Sarah Leigh Added comment: Comment on mode of pathogenicity: Gain of function variants are responsible for Hypercholesterolemia, familial, 3 603776, while loss of function variants are responsible for {Low density lipoprotein cholesterol level QTL 1} 603776.
Inborn errors of metabolism v1.215 PCSK9 Sarah Leigh Mode of pathogenicity for gene: PCSK9 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Undiagnosed metabolic disorders v1.227 PCSK9 Sarah Leigh Added comment: Comment on mode of pathogenicity: Gain of function variants are responsible for Hypercholesterolemia, familial, 3 603776, while loss of function variants are responsible for {Low density lipoprotein cholesterol level QTL 1} 603776.
Undiagnosed metabolic disorders v1.227 PCSK9 Sarah Leigh Mode of pathogenicity for gene: PCSK9 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Inborn errors of metabolism v1.214 PCSK9 Sarah Leigh Classified gene: PCSK9 as Green List (high evidence)
Inborn errors of metabolism v1.214 PCSK9 Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 3 gain of function variants reported in unrelated cases of Hypercholesterolemia, familial, 3 603776 and at least 5 loss of function variants have been reported in unrelated cases of {Low density lipoprotein cholesterol level QTL 1} 603776.
Inborn errors of metabolism v1.214 PCSK9 Sarah Leigh Gene: pcsk9 has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.214 PCSK9 Sarah Leigh Phenotypes for gene: PCSK9 were changed from Hypercholesterolemia, familial, 3 603776; {Low density lipoprotein cholesterol level QTL 1} 60377 to Hypercholesterolemia, familial, 3 603776; {Low density lipoprotein cholesterol level QTL 1} 603776
Undiagnosed metabolic disorders v1.226 PCSK9 Sarah Leigh Classified gene: PCSK9 as Green List (high evidence)
Undiagnosed metabolic disorders v1.226 PCSK9 Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 3 gain of function variants reported in unrelated cases of Hypercholesterolemia, familial, 3 603776 and at least 5 loss of function variants have been reported in unrelated cases of {Low density lipoprotein cholesterol level QTL 1} 603776.
Undiagnosed metabolic disorders v1.226 PCSK9 Sarah Leigh Gene: pcsk9 has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.213 PCSK9 Sarah Leigh Publications for gene: PCSK9 were set to 27604308; 12730697; 14727179; 15772090; 15654334; 16909389
Inborn errors of metabolism v1.213 PCSK9 Sarah Leigh Publications for gene: PCSK9 were set to 27604308
Undiagnosed metabolic disorders v1.225 PCSK9 Sarah Leigh Publications for gene: PCSK9 were set to 27604308
Undiagnosed metabolic disorders v1.224 PCSK9 Sarah Leigh Added comment: Comment on phenotypes: (Inherited hypercholesterolaemias)
Undiagnosed metabolic disorders v1.224 PCSK9 Sarah Leigh Phenotypes for gene: PCSK9 were changed from Autosomal dominant hypercholesterolemia-3 (Inherited hypercholesterolaemias); Familial hypercholesterolaemia to Hypercholesterolemia, familial, 3 603776; {Low density lipoprotein cholesterol level QTL 1} 603776
Undiagnosed metabolic disorders v1.223 PCSK9 Sarah Leigh Deleted their comment
Inborn errors of metabolism v1.212 PCSK9 Sarah Leigh Added comment: Comment on phenotypes: (Inherited hypercholesterolaemias)
Inborn errors of metabolism v1.212 PCSK9 Sarah Leigh Phenotypes for gene: PCSK9 were changed from Familial hypercholesterolaemia; Autosomal dominant hypercholesterolemia-3 (Inherited hypercholesterolaemias) to Hypercholesterolemia, familial, 3 603776; {Low density lipoprotein cholesterol level QTL 1} 60377
Inborn errors of metabolism v1.211 PCK1 Sarah Leigh Classified gene: PCK1 as Green List (high evidence)
Inborn errors of metabolism v1.211 PCK1 Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 3 variants reported in unrelated cases.
Inborn errors of metabolism v1.211 PCK1 Sarah Leigh Gene: pck1 has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.210 PCK1 Sarah Leigh Classified gene: PCK1 as Green List (high evidence)
Inborn errors of metabolism v1.210 PCK1 Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 3 variants reported in unrelated cases.
Inborn errors of metabolism v1.210 PCK1 Sarah Leigh Gene: pck1 has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.210 PCK1 Sarah Leigh Classified gene: PCK1 as Green List (high evidence)
Inborn errors of metabolism v1.210 PCK1 Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 3 variants reported in unrelated cases.
Inborn errors of metabolism v1.210 PCK1 Sarah Leigh Gene: pck1 has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.223 PCK1 Sarah Leigh Classified gene: PCK1 as Green List (high evidence)
Undiagnosed metabolic disorders v1.223 PCK1 Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 3 variants reported in unrelated cases.
Undiagnosed metabolic disorders v1.223 PCK1 Sarah Leigh Gene: pck1 has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.209 PCK1 Sarah Leigh Publications for gene: PCK1 were set to 27604308; 24863970; 26971250
Inborn errors of metabolism v1.208 PCK1 Sarah Leigh Publications for gene: PCK1 were set to 27604308; 24863970; 26971250
Undiagnosed metabolic disorders v1.222 PCK1 Sarah Leigh Publications for gene: PCK1 were set to 27604308
Inborn errors of metabolism v1.208 PCK1 Sarah Leigh Publications for gene: PCK1 were set to 27604308; 24863970; 26971250
Inborn errors of metabolism v1.207 PCK1 Sarah Leigh Publications for gene: PCK1 were set to 27604308
Inborn errors of metabolism v1.207 PCK1 Sarah Leigh Added comment: Comment on phenotypes: Phosphoenolpyruvate carboxykinase deficiency (Disorders of gluconeogenesis);Cytosolic phosphoenolpyruvate carboxykinase (PEPCK))
Inborn errors of metabolism v1.207 PCK1 Sarah Leigh Phenotypes for gene: PCK1 were changed from Phosphoenolpyruvate carboxykinase deficiency (Disorders of gluconeogenesis); ?Phosphoenolpyruvate carboxykinase-1, cytosolic, deficiency; (PCK1 DEFICIENCY, Cytosolic phosphoenolpyruvate carboxykinase (PEPCK)) to ?Phosphoenolpyruvate carboxykinase deficiency, cytosolic 261680
Undiagnosed metabolic disorders v1.221 PCK1 Sarah Leigh Added comment: Comment on phenotypes: Phosphoenolpyruvate carboxykinase deficiency (Disorders of gluconeogenesis);Cytosolic phosphoenolpyruvate carboxykinase (PEPCK))
Undiagnosed metabolic disorders v1.221 PCK1 Sarah Leigh Phenotypes for gene: PCK1 were changed from Phosphoenolpyruvate carboxykinase deficiency (Disorders of gluconeogenesis); ?Phosphoenolpyruvate carboxykinase-1, cytosolic, deficiency; (PCK1 DEFICIENCY, Cytosolic phosphoenolpyruvate carboxykinase (PEPCK)) to ?Phosphoenolpyruvate carboxykinase deficiency, cytosolic 261680
Inborn errors of metabolism v1.206 PANK2 Sarah Leigh Publications for gene: PANK2 were set to 27604308; 11479594; 12510040; 12058097; 14638969; 16240131
Inborn errors of metabolism v1.206 PANK2 Sarah Leigh Publications for gene: PANK2 were set to 27604308
Undiagnosed metabolic disorders v1.220 PANK2 Sarah Leigh Publications for gene: PANK2 were set to 27604308
Inborn errors of metabolism v1.205 PANK2 Sarah Leigh Classified gene: PANK2 as Green List (high evidence)
Inborn errors of metabolism v1.205 PANK2 Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 13 variants reported for Neurodegeneration with brain iron accumulation 234200 and 3 variants in 2 unrelated cases of HARP syndrome 607236.
Inborn errors of metabolism v1.205 PANK2 Sarah Leigh Gene: pank2 has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.219 PANK2 Sarah Leigh Added comment: Comment on phenotypes: (NBIA) (Disorder of iron metabolism);Early onset dystonia;Parkinson Disease and Complex Parkinsonism;Posterior segment abnormalities
Undiagnosed metabolic disorders v1.219 PANK2 Sarah Leigh Phenotypes for gene: PANK2 were changed from HARP syndrome 607236; Neurodegeneration with brain iron accumulation 234200Pantothenate kinases deficiency (Other disorders of vitamins and cofactors); Neurodegeneration with brain iron accumulation (NBIA) (Disorder of iron metabolism); Early onset dystonia; Parkinson Disease and Complex Parkinsonism; Posterior segment abnormalities to HARP syndrome 607236; Neurodegeneration with brain iron accumulation 234200
Inborn errors of metabolism v1.205 PANK2 Sarah Leigh Classified gene: PANK2 as Green List (high evidence)
Inborn errors of metabolism v1.205 PANK2 Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 13 variants reported for Neurodegeneration with brain iron accumulation 234200 and 3 variants in 2 unrelated cases of HARP syndrome 607236.
Inborn errors of metabolism v1.205 PANK2 Sarah Leigh Gene: pank2 has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.218 PANK2 Sarah Leigh Classified gene: PANK2 as Green List (high evidence)
Undiagnosed metabolic disorders v1.218 PANK2 Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 13 variants reported for Neurodegeneration with brain iron accumulation 234200 and 3 variants in 2 unrelated cases of HARP syndrome 607236.
Undiagnosed metabolic disorders v1.218 PANK2 Sarah Leigh Gene: pank2 has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.204 PANK2 Sarah Leigh Added comment: Comment on phenotypes: (Disorder of iron metabolism);Pantothenate kinases deficiency (Other disorders of vitamins and cofactors)
Inborn errors of metabolism v1.204 PANK2 Sarah Leigh Phenotypes for gene: PANK2 were changed from Neurodegeneration with brain iron accumulation 1, 234200HARP syndrome, 607236; Early onset dystonia; Posterior segment abnormalities; Parkinson Disease and Complex Parkinsonism; Neurodegeneration with brain iron accumulation (NBIA) (Disorder of iron metabolism); Pantothenate kinases deficiency (Other disorders of vitamins and cofactors) to HARP syndrome 607236; Neurodegeneration with brain iron accumulation 234200
Undiagnosed metabolic disorders v1.217 PANK2 Sarah Leigh Added comment: Comment on phenotypes: (Disorder of iron metabolism);Early onset dystonia;Parkinson Disease and Complex Parkinsonism;Posterior segment abnormalities
Undiagnosed metabolic disorders v1.217 PANK2 Sarah Leigh Phenotypes for gene: PANK2 were changed from Pantothenate kinases deficiency (Other disorders of vitamins and cofactors); Neurodegeneration with brain iron accumulation (NBIA) (Disorder of iron metabolism); Early onset dystonia; Parkinson Disease and Complex Parkinsonism; Posterior segment abnormalities to HARP syndrome 607236; Neurodegeneration with brain iron accumulation 234200Pantothenate kinases deficiency (Other disorders of vitamins and cofactors); Neurodegeneration with brain iron accumulation (NBIA) (Disorder of iron metabolism); Early onset dystonia; Parkinson Disease and Complex Parkinsonism; Posterior segment abnormalities
Undiagnosed metabolic disorders v1.216 PANK2 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.216 PANK2 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.216 PANK2 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.216 PANK2 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.216 PANK2 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.216 OPLAH Sarah Leigh Classified gene: OPLAH as Amber List (moderate evidence)
Undiagnosed metabolic disorders v1.216 OPLAH Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 3 variants have been reported. It is not clear whether the mode of inheritance is biallelic or monoallelic as homozygous and heterozygote cases have been seen. The PMID 21651516 reports two sibs who are homozygous for a terminating variant, the younger brother is 5-oxoprolinase deficiency, however, his clinically unaffected sister just has increased 5-oxoproline excretion.
Undiagnosed metabolic disorders v1.216 OPLAH Sarah Leigh Gene: oplah has been classified as Amber List (Moderate Evidence).
Undiagnosed metabolic disorders v1.215 OPLAH Sarah Leigh Publications for gene: OPLAH were set to 27604308
Inborn errors of metabolism v1.203 OPLAH Sarah Leigh Added comment: Comment on phenotypes: Oxoprolinuria (Disorders of the gamma-glutamyl cycle)
Inborn errors of metabolism v1.203 OPLAH Sarah Leigh Phenotypes for gene: OPLAH were changed from Oxoprolinuria (Disorders of the gamma-glutamyl cycle); 5-oxoprolinase deficiency, 260005 to 5-oxoprolinase deficiency 260005
Undiagnosed metabolic disorders v1.214 OPLAH Sarah Leigh Added comment: Comment on phenotypes: Oxoprolinuria (Disorders of the gamma-glutamyl cycle)
Undiagnosed metabolic disorders v1.214 OPLAH Sarah Leigh Phenotypes for gene: OPLAH were changed from Oxoprolinuria (Disorders of the gamma-glutamyl cycle); 5-oxoprolinase deficiency, 260005 to 5-oxoprolinase deficiency 260005
Inborn errors of metabolism v1.202 OPLAH Sarah Leigh Classified gene: OPLAH as Amber List (moderate evidence)
Inborn errors of metabolism v1.202 OPLAH Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 3 variants have been reported. It is not clear whether the mode of inheritance is biallelic or monoallelic as homozygous and heterozygote cases have been seen. The PMID 21651516 reports two sibs who are homozygous for a terminating variant, the younger brother is 5-oxoprolinase deficiency, however, his clinically unaffected sister just has increased 5-oxoproline excretion.
Inborn errors of metabolism v1.202 OPLAH Sarah Leigh Gene: oplah has been classified as Amber List (Moderate Evidence).
Inborn errors of metabolism v1.201 OPLAH Sarah Leigh Publications for gene: OPLAH were set to 27604308
Inborn errors of metabolism v1.200 OCRL Sarah Leigh Classified gene: OCRL as Green List (high evidence)
Inborn errors of metabolism v1.200 OCRL Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene for both Dent disease 2 300555 and Lowe syndrome 309000. At least 5variants reported in Dent disease 2 300555 and 4 variants in Lowe syndrome 309000.
Inborn errors of metabolism v1.200 OCRL Sarah Leigh Gene: ocrl has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.200 OCRL Sarah Leigh Classified gene: OCRL as Green List (high evidence)
Inborn errors of metabolism v1.200 OCRL Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene for both Dent disease 2 300555 and Lowe syndrome 309000. At least 5variants reported in Dent disease 2 300555 and 4 variants in Lowe syndrome 309000.
Inborn errors of metabolism v1.200 OCRL Sarah Leigh Gene: ocrl has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.213 OCRL Sarah Leigh Classified gene: OCRL as Green List (high evidence)
Undiagnosed metabolic disorders v1.213 OCRL Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene for both Dent disease 2 300555 and Lowe syndrome 309000. At least 5variants reported in Dent disease 2 300555 and 4 variants in Lowe syndrome 309000.
Undiagnosed metabolic disorders v1.213 OCRL Sarah Leigh Gene: ocrl has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.199 OCRL Sarah Leigh Added comment: Comment on phenotypes: Lowe syndrome (Disorders of amino acid transport);Renal tract calcification (or Nephrolithiasis/nephrocalcinosis);Intellectual disability;Intellectual_disability;Cataracts
Inborn errors of metabolism v1.199 OCRL Sarah Leigh Phenotypes for gene: OCRL were changed from Dent disease 2 300555; Lowe syndrome 309000 to Dent disease 2 300555; Lowe syndrome 309000
Inborn errors of metabolism v1.199 OCRL Sarah Leigh Added comment: Comment on phenotypes: Lowe syndrome (Disorders of amino acid transport);Renal tract calcification (or Nephrolithiasis/nephrocalcinosis);Intellectual disability;Intellectual_disability;Cataracts
Inborn errors of metabolism v1.199 OCRL Sarah Leigh Phenotypes for gene: OCRL were changed from Lowe syndrome (Disorders of amino acid transport); Renal tract calcification (or Nephrolithiasis/nephrocalcinosis); Intellectual disability; Intellectual_disability; Cataracts to Dent disease 2 300555; Lowe syndrome 309000
Undiagnosed metabolic disorders v1.212 OCRL Sarah Leigh Added comment: Comment on phenotypes: Lowe syndrome (Disorders of amino acid transport);Cataracts;Intellectual disability;Intellectual_disability;Renal tract calcification (or Nephrolithiasis/nephrocalcinosis)
Undiagnosed metabolic disorders v1.212 OCRL Sarah Leigh Phenotypes for gene: OCRL were changed from Lowe syndrome (Disorders of amino acid transport); Cataracts; Intellectual disability; Intellectual_disability; Renal tract calcification (or Nephrolithiasis/nephrocalcinosis) to Dent disease 2 300555; Lowe syndrome 309000
Inborn errors of metabolism v1.198 OCRL Sarah Leigh Phenotypes for gene: OCRL were changed from Lowe syndrome (Disorders of amino acid transport); Renal tract calcification (or Nephrolithiasis/nephrocalcinosis); Intellectual disability; Intellectual_disability; Cataracts to Lowe syndrome (Disorders of amino acid transport); Renal tract calcification (or Nephrolithiasis/nephrocalcinosis); Intellectual disability; Intellectual_disability; Cataracts
Inborn errors of metabolism v1.197 OCRL Sarah Leigh Publications for gene: OCRL were set to 27604308
Undiagnosed metabolic disorders v1.211 OCRL Sarah Leigh Publications for gene: OCRL were set to 27604308
Inborn errors of metabolism v1.196 OCRL Sarah Leigh Added comment: Comment on phenotypes: Dent disease 2 300555;Lowe syndrome 309000
Inborn errors of metabolism v1.196 OCRL Sarah Leigh Phenotypes for gene: OCRL were changed from Lowe syndrome (Disorders of amino acid transport); Renal tract calcification (or Nephrolithiasis/nephrocalcinosis); Intellectual disability; Intellectual_disability; Cataracts to Lowe syndrome (Disorders of amino acid transport); Renal tract calcification (or Nephrolithiasis/nephrocalcinosis); Intellectual disability; Intellectual_disability; Cataracts
Undiagnosed metabolic disorders v1.210 OCRL Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.210 OCRL Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.210 OCRL Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.210 OCRL Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.210 OCRL Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.210 OCRL Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.210 OCRL Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.210 NDUFB9 Sarah Leigh Classified gene: NDUFB9 as Amber List (moderate evidence)
Undiagnosed metabolic disorders v1.210 NDUFB9 Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 1 variant reported, together with supportive functional studies.
Undiagnosed metabolic disorders v1.210 NDUFB9 Sarah Leigh Gene: ndufb9 has been classified as Amber List (Moderate Evidence).
Undiagnosed metabolic disorders v1.209 NDUFB9 Sarah Leigh Added comment: Comment on publications: PMID: 22200994 Reports one probound heterozygous for a variant (c.140G>T, p.Arg47Leu) within NDUFB9 with parents not available for genetic testing, and in vitro complement studies in patient fibroblasts showed wildtype NDUFB9 did not rescue complex I activity, therefore was deemed not pathogenic. Reports two brothers homozygous for a variant in the gene, with parents who are heterozygous carriers (c.191T>C, p.Leu64Pro). In vitro, fibroblasts from the proband showed low complex I activity, and wildtype NDUFB9 rescued complex I activity.
Undiagnosed metabolic disorders v1.209 NDUFB9 Sarah Leigh Publications for gene: NDUFB9 were set to 27604308
Inborn errors of metabolism v1.195 NDUFB9 Sarah Leigh Classified gene: NDUFB9 as Amber List (moderate evidence)
Inborn errors of metabolism v1.195 NDUFB9 Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 1 variant reported, together with supportive functional studies.
Inborn errors of metabolism v1.195 NDUFB9 Sarah Leigh Gene: ndufb9 has been classified as Amber List (Moderate Evidence).
Inborn errors of metabolism v1.194 NDUFB9 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.208 NDUFB9 Sarah Leigh Phenotypes for gene: NDUFB9 were changed from Complex I (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits); ?Mitochondrial complex I deficiency to ?Mitochondrial complex I deficiency, nuclear type 24 618245
Inborn errors of metabolism v1.194 NDUFB9 Sarah Leigh Phenotypes for gene: NDUFB9 were changed from ?Mitochondrial complex I deficiency, 252010; Complex I (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits); ?Mitochondrial complex I deficiency; Isolated complex I deficiency to ?Mitochondrial complex I deficiency, nuclear type 24 618245
Inborn errors of metabolism v1.193 NDUFB9 Sarah Leigh Added comment: Comment on publications: PMID: 22200994 Reports one probound heterozygous for a variant (c.140G>T, p.Arg47Leu) within NDUFB9 with parents not available for genetic testing, and in vitro complement studies in patient fibroblasts showed wildtype NDUFB9 did not rescue complex I activity, therefore was deemed not pathogenic. Reports two brothers homozygous for a variant in the gene, with parents who are heterozygous carriers (c.191T>C, p.Leu64Pro). In vitro, fibroblasts from the proband showed low complex I activity, and wildtype NDUFB9 rescued complex I activity.
Inborn errors of metabolism v1.193 NDUFB9 Sarah Leigh Publications for gene: NDUFB9 were set to PMID: 22200994 Reports one probound heterozygous for a variant (c.140G>T, p.Arg47Leu) within NDUFB9 with parents not available for genetic testing, and in vitro complement studies in patient fibroblasts showed wildtype NDUFB9 did not rescue complex I activity, therefore was deemed not pathogenic. Reports two brothers homozygous for a variant in the gene, with parents who are heterozygous carriers (c.191T>C, p.Leu64Pro). In vitro, fibroblasts from the proband showed low complex I activity, and wildtype NDUFB9 rescued complex I activity.
Inborn errors of metabolism v1.192 MVK Sarah Leigh Mode of inheritance for gene: MVK was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Undiagnosed metabolic disorders v1.207 MVK Sarah Leigh Mode of inheritance for gene: MVK was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Undiagnosed metabolic disorders v1.206 MVK Sarah Leigh changed review comment from: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 8 variants reported in Hyper-IgD syndrome 260920, 9 variants reported in Mevalonic aciduria 610377 and 8 variants reported in Porokeratosis 3, multiple types 175900.; to: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. Numerous variants reported for each phenotype.
Inborn errors of metabolism v1.191 MVK Sarah Leigh Publications for gene: MVK were set to 27604308
Undiagnosed metabolic disorders v1.206 MVK Sarah Leigh Publications for gene: MVK were set to 27604308
Inborn errors of metabolism v1.190 MVK Sarah Leigh Classified gene: MVK as Green List (high evidence)
Inborn errors of metabolism v1.190 MVK Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 8 variants reported in Hyper-IgD syndrome 260920, 9 variants reported in Mevalonic aciduria 610377 and 8 variants reported in Porokeratosis 3, multiple types 175900.
Inborn errors of metabolism v1.190 MVK Sarah Leigh Gene: mvk has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.205 MVK Sarah Leigh Classified gene: MVK as Green List (high evidence)
Undiagnosed metabolic disorders v1.205 MVK Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 8 variants reported in Hyper-IgD syndrome 260920, 9 variants reported in Mevalonic aciduria 610377 and 8 variants reported in Porokeratosis 3, multiple types 175900.
Undiagnosed metabolic disorders v1.205 MVK Sarah Leigh Gene: mvk has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.204 MVK Sarah Leigh Deleted their comment
Inborn errors of metabolism v1.189 MVK Sarah Leigh Added comment: Comment on phenotypes: Infantile enterocolitis & monogenic inflammatory bowel disease;Mevalonate kinase deficiency (Disorders of sterol biosynthesis)
Inborn errors of metabolism v1.189 MVK Sarah Leigh Phenotypes for gene: MVK were changed from Infantile enterocolitis & monogenic inflammatory bowel disease; Mevalonate kinase deficiency (Disorders of sterol biosynthesis) to Hyper-IgD syndrome 260920; Mevalonic aciduria 610377; Porokeratosis 3, multiple types 175900
Undiagnosed metabolic disorders v1.204 MVK Sarah Leigh Added comment: Comment on phenotypes: Mevalonate kinase deficiency (Disorders of sterol biosynthesis);Infantile enterocolitis & monogenic inflammatory bowel disease
Undiagnosed metabolic disorders v1.204 MVK Sarah Leigh Phenotypes for gene: MVK were changed from Mevalonate kinase deficiency (Disorders of sterol biosynthesis); Infantile enterocolitis & monogenic inflammatory bowel disease to Hyper-IgD syndrome 260920; Mevalonic aciduria 610377; Porokeratosis 3, multiple types 175900
Inborn errors of metabolism v1.188 MTPAP Sarah Leigh Added comment: Comment on phenotypes: Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)
Inborn errors of metabolism v1.188 MTPAP Sarah Leigh Phenotypes for gene: MTPAP were changed from ?Spastic ataxia 4, autosomal recessive 613672; Ataxia, spastic, 4, 613672; ?Spastic ataxia 4, autosomal recessive, 613672; Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only) to ?Spastic ataxia 4, autosomal recessive 613672
Undiagnosed metabolic disorders v1.203 MTPAP Sarah Leigh Added comment: Comment on phenotypes: Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)
Undiagnosed metabolic disorders v1.203 MTPAP Sarah Leigh Phenotypes for gene: MTPAP were changed from Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only); ?Spastic ataxia 4, autosomal recessive, 613672 to ?Spastic ataxia 4, autosomal recessive, 613672
Membranoproliferative glomerulonephritis v2.0 Ellen McDonagh promoted panel to version 2.0
Membranoproliferative glomerulonephritis v1.17 Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease; GMS signed-off
Undiagnosed metabolic disorders v1.202 MTPAP Sarah Leigh Publications for gene: MTPAP were set to 27604308
Undiagnosed metabolic disorders v1.201 MTPAP Sarah Leigh Classified gene: MTPAP as Green List (high evidence)
Undiagnosed metabolic disorders v1.201 MTPAP Sarah Leigh Added comment: Comment on list classification: Associated with phenotype in OMIM and not in Gen2Phen. At least 2 variants identified in unrelated cases, and supportive functional studies.
Undiagnosed metabolic disorders v1.201 MTPAP Sarah Leigh Gene: mtpap has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.200 MTFMT Sarah Leigh Classified gene: MTFMT as Green List (high evidence)
Undiagnosed metabolic disorders v1.200 MTFMT Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 8 variants reported.
Undiagnosed metabolic disorders v1.200 MTFMT Sarah Leigh Gene: mtfmt has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.187 MTFMT Sarah Leigh Publications for gene: MTFMT were set to 21907147; 27564080; 23499752; 24461907
Undiagnosed metabolic disorders v1.199 MTFMT Sarah Leigh Publications for gene: MTFMT were set to 27604308
Undiagnosed metabolic disorders v1.198 MTFMT Sarah Leigh Added comment: Comment on phenotypes: Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)).
Undiagnosed metabolic disorders v1.198 MTFMT Sarah Leigh Phenotypes for gene: MTFMT were changed from Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Inherited white matter disorders to Combined oxidative phosphorylation deficiency 15 614947; Mitochondrial complex I deficiency, nuclear type 27 618248
Inborn errors of metabolism v1.186 MTFMT Sarah Leigh Added comment: Comment on phenotypes: Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)).
Inborn errors of metabolism v1.186 MTFMT Sarah Leigh Phenotypes for gene: MTFMT were changed from Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Combined oxidative phosphorylation deficiency 15, 614947; Inherited white matter disorders; Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Mitochondrial complex I deficiency, nuclear type 27 618248 to Combined oxidative phosphorylation deficiency 15 614947; Mitochondrial complex I deficiency, nuclear type 27 618248
Undiagnosed metabolic disorders v1.197 MTFMT Sarah Leigh Deleted their comment
Atypical haemolytic uraemic syndrome v2.0 Ellen McDonagh promoted panel to version 2.0
Atypical haemolytic uraemic syndrome v1.22 Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease; GMS signed-off
Undiagnosed metabolic disorders v1.197 MRPL3 Sarah Leigh Classified gene: MRPL3 as Green List (high evidence)
Undiagnosed metabolic disorders v1.197 MRPL3 Sarah Leigh Added comment: Comment on list classification: This gene was rated as Green due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter (May 2019) on behalf of GMS mitochondrial specialist test group: 2 unrelated families (4 sibs + 1 unrelated case) and functional studies. From panel: Possible mitochondrial disorder - nuclear genes (Version 0.187).
Undiagnosed metabolic disorders v1.197 MRPL3 Sarah Leigh Gene: mrpl3 has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.196 MRPL3 Sarah Leigh Publications for gene: MRPL3 were set to 27604308
Hearing loss v2.0 Ellen McDonagh promoted panel to version 2.0
Hearing loss v1.128 Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS signed-off
Inborn errors of metabolism v1.185 MRPL3 Sarah Leigh Added comment: Comment on phenotypes: Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only))
Inborn errors of metabolism v1.185 MRPL3 Sarah Leigh Phenotypes for gene: MRPL3 were changed from Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Combined oxidative phosphorylation deficiency 9, 614582 to Combined oxidative phosphorylation deficiency 9 614582
Undiagnosed metabolic disorders v1.195 MRPL3 Sarah Leigh Added comment: Comment on phenotypes: Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only))
Undiagnosed metabolic disorders v1.195 MRPL3 Sarah Leigh Phenotypes for gene: MRPL3 were changed from Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Combined oxidative phosphorylation deficiency 9, 614582 to Combined oxidative phosphorylation deficiency 9, 614582
Undiagnosed metabolic disorders v1.194 MOCS2 Sarah Leigh Classified gene: MOCS2 as Green List (high evidence)
Undiagnosed metabolic disorders v1.194 MOCS2 Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 9 variants reported in at least 8 unrelated cases, together with supportive functional studies.
Undiagnosed metabolic disorders v1.194 MOCS2 Sarah Leigh Gene: mocs2 has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.184 MOCS2 Sarah Leigh Classified gene: MOCS2 as Green List (high evidence)
Inborn errors of metabolism v1.184 MOCS2 Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 9 variants reported in at least 8 unrelated cases, together with supportive functional studies.
Inborn errors of metabolism v1.184 MOCS2 Sarah Leigh Gene: mocs2 has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.183 MOCS2 Sarah Leigh Publications for gene: MOCS2 were set to 27604308
Undiagnosed metabolic disorders v1.193 MOCS2 Sarah Leigh Publications for gene: MOCS2 were set to 27604308
Undiagnosed metabolic disorders v1.192 MOCS2 Sarah Leigh Added comment: Comment on phenotypes: Mo cofactor deficiency, complementation group B (Disorders of molybdenum cofactor metabolism);Intellectual disability
Undiagnosed metabolic disorders v1.192 MOCS2 Sarah Leigh Phenotypes for gene: MOCS2 were changed from Mo cofactor deficiency, complementation group B (Disorders of molybdenum cofactor metabolism); Intellectual disability to Molybdenum cofactor deficiency B 252160
Undiagnosed metabolic disorders v1.191 MOCS2 Sarah Leigh Deleted their comment
Inborn errors of metabolism v1.182 MOCS2 Sarah Leigh Added comment: Comment on phenotypes: Intellectual disability;Mo cofactor deficiency, complementation group B (Disorders of molybdenum cofactor metabolism)
Inborn errors of metabolism v1.182 MOCS2 Sarah Leigh Phenotypes for gene: MOCS2 were changed from Intellectual disability; Mo cofactor deficiency, complementation group B (Disorders of molybdenum cofactor metabolism) to Molybdenum cofactor deficiency B 252160
Undiagnosed metabolic disorders v1.191 MOCS1 Sarah Leigh Classified gene: MOCS1 as Green List (high evidence)
Undiagnosed metabolic disorders v1.191 MOCS1 Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 5 variants reported unrelated cases.
Undiagnosed metabolic disorders v1.191 MOCS1 Sarah Leigh Gene: mocs1 has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.181 MOCS1 Sarah Leigh Publications for gene: MOCS1 were set to 27604308
Undiagnosed metabolic disorders v1.190 MOCS1 Sarah Leigh Publications for gene: MOCS1 were set to 27604308
Inborn errors of metabolism v1.180 MOCS1 Sarah Leigh Classified gene: MOCS1 as Green List (high evidence)
Inborn errors of metabolism v1.180 MOCS1 Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 5 variants reported unrelated cases.
Inborn errors of metabolism v1.180 MOCS1 Sarah Leigh Gene: mocs1 has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.189 MOCS1 Sarah Leigh Added comment: Comment on phenotypes: Mo cofactor deficiency, complementation group A (Disorders of molybdenum cofactor metabolism);Intellectual disability
Undiagnosed metabolic disorders v1.189 MOCS1 Sarah Leigh Phenotypes for gene: MOCS1 were changed from Mo cofactor deficiency, complementation group A (Disorders of molybdenum cofactor metabolism); Intellectual disability to Molybdenum cofactor deficiency A 252150
Inborn errors of metabolism v1.179 MOCS1 Sarah Leigh Added comment: Comment on phenotypes: Intellectual disability;Mo cofactor deficiency, complementation group A (Disorders of molybdenum cofactor metabolism)
Inborn errors of metabolism v1.179 MOCS1 Sarah Leigh Phenotypes for gene: MOCS1 were changed from Intellectual disability; Mo cofactor deficiency, complementation group A (Disorders of molybdenum cofactor metabolism) to Molybdenum cofactor deficiency A 252150
Undiagnosed metabolic disorders v1.188 MOCS1 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.188 MAOA Sarah Leigh Publications for gene: MAOA were set to 27604308
Inborn errors of metabolism v1.178 MAOA Sarah Leigh Phenotypes for gene: MAOA were changed from Brunner syndrome to Brunner syndrome 300615; {Antisocial behavior} 300615
Inborn errors of metabolism v1.177 MAOA Sarah Leigh Deleted their comment
Inborn errors of metabolism v1.177 MAOA Sarah Leigh Publications for gene: MAOA were set to 27604308
Inborn errors of metabolism v1.176 MAOA Sarah Leigh Classified gene: MAOA as Green List (high evidence)
Inborn errors of metabolism v1.176 MAOA Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 4 variants reported in unrelated cases.
Inborn errors of metabolism v1.176 MAOA Sarah Leigh Gene: maoa has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.176 MAOA Sarah Leigh Classified gene: MAOA as Green List (high evidence)
Inborn errors of metabolism v1.176 MAOA Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 4 variants reported in unrelated cases.
Inborn errors of metabolism v1.176 MAOA Sarah Leigh Gene: maoa has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.187 MAOA Sarah Leigh Classified gene: MAOA as Green List (high evidence)
Undiagnosed metabolic disorders v1.187 MAOA Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 4 variants reported in unrelated cases.
Undiagnosed metabolic disorders v1.187 MAOA Sarah Leigh Gene: maoa has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.186 MAGT1 Sarah Leigh Publications for gene: MAGT1 were set to 27604308
Inborn errors of metabolism v1.175 MAGT1 Sarah Leigh Classified gene: MAGT1 as Green List (high evidence)
Inborn errors of metabolism v1.175 MAGT1 Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM and as possible Gen2Phen gene. At least 3 variants reported in unrelated cases, together with mouse knock-out model (PMID 29581357).
Inborn errors of metabolism v1.175 MAGT1 Sarah Leigh Gene: magt1 has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.185 MAGT1 Sarah Leigh Classified gene: MAGT1 as Green List (high evidence)
Undiagnosed metabolic disorders v1.185 MAGT1 Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as possible Gen2Phen gene. At least 3 variants reported in unrelated cases, together with mouse knock-out model (PMID 29581357).
Undiagnosed metabolic disorders v1.185 MAGT1 Sarah Leigh Gene: magt1 has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.174 MAGT1 Sarah Leigh Publications for gene: MAGT1 were set to 27604308; 27393411; 29581357; 25956530
Inborn errors of metabolism v1.173 MAGT1 Sarah Leigh Publications for gene: MAGT1 were set to 27604308; 27393411; 29581357
Inborn errors of metabolism v1.172 MAGT1 Sarah Leigh Publications for gene: MAGT1 were set to 27604308; 27393411
Genetic epilepsy syndromes v1.254 SLC2A1 Ellen McDonagh edited their review of gene: SLC2A1: Added comment: Added the tag 'treatable' as a ketogenic diet can help ameloriate symptoms (PMID: 29303961).; Changed publications: 29303961
Intellectual disability v2.1015 SOX4 Louise Daugherty Added comment: Comment on phenotypes: added OMIM MIM id
Intellectual disability v2.1015 SOX4 Louise Daugherty Phenotypes for gene: SOX4 were changed from Syndromic intellectual disability; Global developmental delay; Intellectual disability; Growth delay; Clinodactyly of the 5th finger; facial dysmorphism to Coffin-Siris syndrome 10, 618506; Syndromic intellectual disability; Global developmental delay; Intellectual disability; Growth delay; Clinodactyly of the 5th finger; facial dysmorphism
Intellectual disability v2.1014 KMT2E Louise Daugherty Added comment: Comment on phenotypes: added OMIM MIM id
Intellectual disability v2.1014 KMT2E Louise Daugherty Phenotypes for gene: KMT2E were changed from Global developmental delay; Intellectual disability; Autism; Seizures; Abnormality of skull size to O'Donnell-Luria-Rodan syndrome, 618512; Global developmental delay; Intellectual disability; Autism; Seizures; Abnormality of skull size
Genetic epilepsy syndromes v1.254 SLC2A1 Ellen McDonagh Tag treatable tag was added to gene: SLC2A1.
Genetic epilepsy syndromes v1.254 KMT2E Louise Daugherty Added comment: Comment on phenotypes: added OMIM MIM id
Genetic epilepsy syndromes v1.254 KMT2E Louise Daugherty Phenotypes for gene: KMT2E were changed from Global developmental delay; Intellectual disability; Autism; Seizures; Abnormality of skull size to O'Donnell-Luria-Rodan syndrome, 618512; Global developmental delay; Intellectual disability; Autism; Seizures; Abnormality of skull size
Holoprosencephaly v1.22 CNOT1 Louise Daugherty Phenotypes for gene: CNOT1 were changed from pancreatic agenesis and holoprosencephaly syndrome to Holoprosencephaly 12, with or without pancreatic agenesis, 618500; pancreatic agenesis and holoprosencephaly syndrome
Intellectual disability v2.1013 CNOT1 Louise Daugherty Added comment: Comment on phenotypes: added OMIM MIM id
Intellectual disability v2.1013 CNOT1 Louise Daugherty Phenotypes for gene: CNOT1 were changed from global developmental delay to Holoprosencephaly 12, with or without pancreatic agenesis, 618500; global developmental delay
Intellectual disability v2.1012 CACNA1B Louise Daugherty Added comment: Comment on phenotypes: added OMIM MIM id
Intellectual disability v2.1012 CACNA1B Louise Daugherty Phenotypes for gene: CACNA1B were changed from Progressive Epilepsy-Dyskinesia; Seizures; Abnormality of movement; Intellectual disability; Developmental regression; Global developmental delay to Neurodevelopmental disorder with seizures and nonepileptic hyperkinetic movements, 618497; Progressive Epilepsy-Dyskinesia; Seizures; Abnormality of movement; Intellectual disability; Developmental regression; Global developmental delay
Undiagnosed metabolic disorders v1.184 MAGT1 Sarah Leigh Added comment: Comment on phenotypes: IAP-CDG (Disorders of protein N-glycosylation)
Undiagnosed metabolic disorders v1.184 MAGT1 Sarah Leigh Phenotypes for gene: MAGT1 were changed from IAP-CDG (Disorders of protein N-glycosylation); Combined B and T cell defect to Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia 300853
Inborn errors of metabolism v1.171 MAGT1 Sarah Leigh Added comment: Comment on phenotypes: IAP-CDG (Disorders of protein N-glycosylation)
Genetic epilepsy syndromes v1.253 CACNA1B Louise Daugherty Added comment: Comment on phenotypes: added OMIM MIM id
Genetic epilepsy syndromes v1.253 CACNA1B Louise Daugherty Phenotypes for gene: CACNA1B were changed from Global developmental delay; Developmental regression; Seizures; Intellectual disability; Abnormality of movement; Progressive Epilepsy-Dyskinesia to Neurodevelopmental disorder with seizures and nonepileptic hyperkinetic movements, 618497; Global developmental delay; Developmental regression; Seizures; Intellectual disability; Abnormality of movement; Progressive Epilepsy-Dyskinesia
Inborn errors of metabolism v1.171 MAGT1 Sarah Leigh Phenotypes for gene: MAGT1 were changed from Combined B and T cell defect; Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia 300853; IAP-CDG (Disorders of protein N-glycosylation) to Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia 300853
Undiagnosed metabolic disorders v1.183 MAGT1 Sarah Leigh Deleted their comment
Inborn errors of metabolism v1.170 LIPC Sarah Leigh Phenotypes for gene: LIPC were changed from {Diabetes mellitus, noninsulin-dependent} 125853; Hepatic lipase deficiency 614025; [High density lipoprotein cholesterol level QTL 12] 612797 to Hepatic lipase deficiency, 614025; [High density lipoprotein cholesterol level QTL 12] 612797; {Diabetes mellitus, noninsulin-dependent} 125853
Inborn errors of metabolism v1.170 LIPC Sarah Leigh Publications for gene: LIPC were set to 27604308; 1671786; 12777476; 22464213; 23219720
Inborn errors of metabolism v1.169 LIPC Sarah Leigh Publications for gene: LIPC were set to 27604308
Inborn errors of metabolism v1.169 LIPC Sarah Leigh Classified gene: LIPC as Amber List (moderate evidence)
Inborn errors of metabolism v1.169 LIPC Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 3 variants reported in two unrelated families with Hepatic lipase deficiency, 614025.
Inborn errors of metabolism v1.169 LIPC Sarah Leigh Gene: lipc has been classified as Amber List (Moderate Evidence).
Undiagnosed metabolic disorders v1.183 LIPC Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.183 LIPC Sarah Leigh Classified gene: LIPC as Amber List (moderate evidence)
Undiagnosed metabolic disorders v1.183 LIPC Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 3 variants reported in two unrelated families with Hepatic lipase deficiency, 614025.
Undiagnosed metabolic disorders v1.183 LIPC Sarah Leigh Gene: lipc has been classified as Amber List (Moderate Evidence).
Undiagnosed metabolic disorders v1.182 LIPC Sarah Leigh Classified gene: LIPC as Amber List (moderate evidence)
Undiagnosed metabolic disorders v1.182 LIPC Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 3 variants reported in two unrelated families with Hepatic lipase deficiency, 614025.
Undiagnosed metabolic disorders v1.182 LIPC Sarah Leigh Gene: lipc has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency v1.53 RASGRP1 Louise Daugherty Added comment: Comment on publications: added further publications to further support gene-disease association
Primary immunodeficiency v1.53 RASGRP1 Louise Daugherty Publications for gene: RASGRP1 were set to 30030704; 29282224
Primary immunodeficiency v1.52 RASGRP1 Louise Daugherty Added comment: Comment on phenotypes: added OMIM MIM id
Primary immunodeficiency v1.52 RASGRP1 Louise Daugherty Phenotypes for gene: RASGRP1 were changed from Recurrent pneumonia, herpesvirus infections, EBV associated lymphoma; Diseases of Immune Dysregulation; EBV-induced lymphoma; Immunodeficiency, to Recurrent pneumonia, herpesvirus infections, EBV associated lymphoma; Diseases of Immune Dysregulation; EBV-induced lymphoma; Immunodeficiency; Immunodeficiency 64, 618534
Undiagnosed metabolic disorders v1.181 LIPC Sarah Leigh Publications for gene: LIPC were set to 27604308; 1671786; 12777476; 22464213; 23219720
Undiagnosed metabolic disorders v1.180 LIPC Sarah Leigh Phenotypes for gene: LIPC were changed from {Diabetes mellitus, noninsulin-dependent} 125853; Hepatic lipase deficiency 614025; [High density lipoprotein cholesterol level QTL 12] 612797 to Hepatic lipase deficiency, 614025; [High density lipoprotein cholesterol level QTL 12] 612797; {Diabetes mellitus, noninsulin-dependent} 125853
Limb disorders v1.58 EIF4A3 Eleanor Williams commented on gene: EIF4A3: Associated with Robin sequence with cleft mandible and limb anomalies (#268305) in OMIM and RICHIERI-COSTA-PEREIRA SYNDROME in Gene2Phenotype (confirmed, 5_prime or 3_prime UTR mutation).

PMID: 24360810 - Favaro et al. 2014 - found in Brazilian families with RCPS 17 affected probands were homozygous for the 16-repeat allele in the 5 prime UTR of EIF4A3, and 3 apparently unrelated affected individuals were compound heterozygotes (15 or 16 repeats). All tested parents were heterozygous for the 16-repeat allele, and unaffected siblings either lacked the expanded allele or were heterozygotes. The 15- and 16-repeat allele haplotypes spanning EIF4A3 are consistent with a common origin and corroborate their previous founder effect hypothesis for most Brazilian RCPS-affected individuals. Sequencing of EIF4A3 in five additional Brazilian affected individuals ascertained elsewhererevealed that four of them (, including 2 siblings) were homozygous for the 16-repeat allele. In contrast, the fifth (individual 25) was a compound heterozygote, possessing a 14-repeat allele in trans with a nucleotide change, c.809A>G, p.Asp270Gly. the c.809A>G mutation is embedded in a distinct haplotype, suggesting multiple pathogenic mutational origins in EIF4A3.
EIF4A3 transcript abundance was about 30%–40% lower in affected individuals than in controls in both cell types tested.
Zebrafish morpholinos show underdevelopment of craniofacial cartilage, bone alterations, and clefting of the lower jaw.
Limb disorders v1.58 NCAPG2 Eleanor Williams Classified gene: NCAPG2 as Amber List (moderate evidence)
Limb disorders v1.58 NCAPG2 Eleanor Williams Added comment: Comment on list classification: 2 cases. Zebra fish model does not show limb phenotype.
Limb disorders v1.58 NCAPG2 Eleanor Williams Gene: ncapg2 has been classified as Amber List (Moderate Evidence).
Familial pulmonary fibrosis v1.5 PARN Matthew Edwards reviewed gene: PARN: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 26116823, 25848748; Phenotypes: Pulmonary fibrosis and/or bone marrow failure, telomere-related, 4 (OMIM 616371); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Inherited predisposition to GIST v1.0 Ivone Leong promoted panel to version 1.0
Inherited predisposition to GIST v0.22 Ivone Leong Panel types changed to GMS Rare Disease; GMS signed-off
Rhabdoid tumour predisposition v1.0 Ivone Leong promoted panel to version 1.0
Rhabdoid tumour predisposition v0.9 Ivone Leong Panel types changed to GMS Rare Disease; GMS signed-off
Familial melanoma v1.0 Ivone Leong promoted panel to version 1.0
Familial melanoma v0.24 Ivone Leong Panel types changed to GMS Rare Disease; GMS signed-off
Inherited MMR deficiency (Lynch syndrome) v1.0 Ivone Leong promoted panel to version 1.0
Inherited MMR deficiency (Lynch syndrome) v0.12 Ivone Leong Panel name changed from Inherited MMR deficiency (Lynch syndrome), R210 to Inherited MMR deficiency (Lynch syndrome)
List of related panels changed from to R210
Panel types changed to GMS Rare Disease; GMS signed-off
Inherited ovarian cancer (without breast cancer) v2.0 Ivone Leong promoted panel to version 2.0
Inherited ovarian cancer (without breast cancer) v1.10 Ivone Leong Panel types changed to Rare Disease 100K; GMS Rare Disease; GMS signed-off
Primary immunodeficiency v1.51 PTEN Louise Daugherty changed review comment from: Comment on list classification: Changed from Red to Amber. As discussed with the GMS Neurology Specialist Test Group webex call 28th March 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Amber- publication evidence supplied by expert; to: Comment on list classification: Changed from Red to Amber. As discussed with the GMS Immunology Specialist Test Group webex call 28th March 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Amber- publication evidence supplied by expert
Primary immunodeficiency v1.51 USP18 Louise Daugherty changed review comment from: Comment on publications: Added publications PMID: 31272490, PMID:27325888 suggested by Tracy Briggs (NWGLH) on behalf of the Specialist Test Group to support inclusion of this gene on the panel and a Green rating. Flagged for further discussion with the Specialist Test Group as conflicts with the Amber rating agreed in the webex 28th March 2019; to: Comment on publications: Added publications PMID: 31272490, PMID:27325888 suggested by Tracy Briggs (NWGLH) on behalf of the Specialist Test Group to support inclusion of this gene on the panel and a Green rating. : five PTS patients from two unrelated families. Flagged for further discussion with the Specialist Test Group as conflicts with the Amber rating agreed in the webex 28th March 2019
Primary immunodeficiency v1.51 USP18 Louise Daugherty changed review comment from: Comment on publications: Added publications PMID: 31272490, PMID:27325888 suggested by Tracy Briggs (NWGLH) on behalf of the Specialist Test Group to support inclusion of this gene on the panel and a Green rating. Flagged for further discussion with the Specialist Test Group; to: Comment on publications: Added publications PMID: 31272490, PMID:27325888 suggested by Tracy Briggs (NWGLH) on behalf of the Specialist Test Group to support inclusion of this gene on the panel and a Green rating. Flagged for further discussion with the Specialist Test Group as conflicts with the Amber rating agreed in the webex 28th March 2019
Primary immunodeficiency v1.51 USP18 Louise Daugherty Phenotypes for gene: USP18 were changed from TORCH like syndrome; Autoinflammatory Disorders to TORCH like syndrome; Autoinflammatory Disorders; Pseudo-TORCH syndrome 2, 617397
Primary immunodeficiency v1.50 USP18 Louise Daugherty Added comment: Comment on publications: Added publications PMID: 31272490, PMID:27325888 suggested by Tracy Briggs (NWGLH) on behalf of the Specialist Test Group to support inclusion of this gene on the panel and a Green rating. Flagged for further discussion with the Specialist Test Group
Primary immunodeficiency v1.50 USP18 Louise Daugherty Publications for gene: USP18 were set to
Primary immunodeficiency v1.49 PSMB9 Louise Daugherty Phenotypes for gene: PSMB9 were changed from CANDLE syndrome (Autoinflammation, lipodystrophy, and dermatosis syndrome) to Autoinflammation, lipodystrophy, and dermatosis syndrome; CANDLE syndrome (Autoinflammation, lipodystrophy, and dermatosis syndrome)
Primary immunodeficiency v1.48 PSMB9 Louise Daugherty Added comment: Comment on publications: PMID:26524591 suggested by Tracy Briggs (NWGLH) on behalf of The Specialist Test Group to support inclusion of this gene on the panel.
Primary immunodeficiency v1.48 PSMB9 Louise Daugherty Publications for gene: PSMB9 were set to
Primary immunodeficiency v1.47 PSMA3 Louise Daugherty Phenotypes for gene: PSMA3 were changed from to CANDLE syndrome (Autoinflammation, lipodystrophy, and dermatosis syndrome)
Primary immunodeficiency v1.46 PSMA3 Louise Daugherty Added comment: Comment on publications: PMID:26524591 suggested by Tracy Briggs (NWGLH) on behalf of The Specialist Test Group to support inclusion of this gene on the panel.
Primary immunodeficiency v1.46 PSMA3 Louise Daugherty Publications for gene: PSMA3 were set to
Primary immunodeficiency v1.45 CTC1 Louise Daugherty Added comment: Comment on publications: PMID: 22267198 suggested by Tracy Briggs (NWGLH) on behalf of The Specialist Test Group to support rating of the gene to be Amber
Primary immunodeficiency v1.45 CTC1 Louise Daugherty Added comment: Comment on publications: PMID: 22267198 suggested by Tracy Briggs (NWGLH) on behalf of The Specialist Test Group to support rating of the gene to be Amber
Primary immunodeficiency v1.45 CTC1 Louise Daugherty Publications for gene: CTC1 were set to 22267198
Primary immunodeficiency v1.45 CTC1 Louise Daugherty Publications for gene: CTC1 were set to 22267198
Primary immunodeficiency v1.44 CTC1 Louise Daugherty Publications for gene: CTC1 were set to
Primary immunodeficiency v1.43 PSMB4 Louise Daugherty changed review comment from: added digenic tag - from review comment 'Digenic also reported" from NWGLH (Tracy Briggs); to: added digenic tag - from review comment 'Digenic also reported' from NWGLH (Tracy Briggs)
Primary immunodeficiency v1.43 PSMB9 Louise Daugherty commented on gene: PSMB9: added digenic tag - from review comment 'Digenic also reported' from NWGLH (Tracy Briggs)
Primary immunodeficiency v1.43 PSMB9 Louise Daugherty Tag digenic tag was added to gene: PSMB9.
Primary immunodeficiency v1.43 PSMB4 Louise Daugherty commented on gene: PSMB4: added digenic tag - from review comment 'Digenic also reported" from NWGLH (Tracy Briggs)
Primary immunodeficiency v1.43 PSMB4 Louise Daugherty Tag digenic tag was added to gene: PSMB4.
Primary immunodeficiency v1.43 PTEN Louise Daugherty Classified gene: PTEN as Amber List (moderate evidence)
Primary immunodeficiency v1.43 PTEN Louise Daugherty Added comment: Comment on list classification: Changed from Red to Amber. As discussed with the GMS Neurology Specialist Test Group webex call 28th March 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Amber- publication evidence supplied by expert
Primary immunodeficiency v1.43 PTEN Louise Daugherty Gene: pten has been classified as Amber List (Moderate Evidence).
Cystic renal disease v1.58 Eleanor Williams List of related panels changed from Cystic renal disease - PKD1 to Cystic renal disease - PKD1; R193
Genetic epilepsy syndromes v1.252 ISCA-46290-Gain Rebecca Foulger Haploinsufficiency Score for ISCA-46290-Gain was changed from to None.
Source NHS GMS was added to Region: ISCA-46290-Gain.
Genetic epilepsy syndromes v1.251 ISCA-37493-Loss Rebecca Foulger Triplosensitivity Score for ISCA-37493-Loss was changed from to None.
Source NHS GMS was added to Region: ISCA-37493-Loss.
Genetic epilepsy syndromes v1.250 ISCA-37478-Loss Rebecca Foulger Triplosensitivity Score for ISCA-37478-Loss was changed from to None.
Source NHS GMS was added to Region: ISCA-37478-Loss.
Genetic epilepsy syndromes v1.249 ISCA-37478-Gain Rebecca Foulger Haploinsufficiency Score for ISCA-37478-Gain was changed from to None.
Source NHS GMS was added to Region: ISCA-37478-Gain.
Genetic epilepsy syndromes v1.248 ISCA-37434-Loss Rebecca Foulger Triplosensitivity Score for ISCA-37434-Loss was changed from to None.
Source NHS GMS was added to Region: ISCA-37434-Loss.
Genetic epilepsy syndromes v1.247 ISCA-37432-Gain Rebecca Foulger Haploinsufficiency Score for ISCA-37432-Gain was changed from to None.
Source NHS GMS was added to Region: ISCA-37432-Gain.
Genetic epilepsy syndromes v1.246 ISCA-37430-Loss Rebecca Foulger Triplosensitivity Score for ISCA-37430-Loss was changed from to None.
Source NHS GMS was added to Region: ISCA-37430-Loss.
Genetic epilepsy syndromes v1.245 ISCA-37429-Loss Rebecca Foulger Triplosensitivity Score for ISCA-37429-Loss was changed from to None.
Source NHS GMS was added to Region: ISCA-37429-Loss.
Genetic epilepsy syndromes v1.244 ISCA-37423-Gain Rebecca Foulger Haploinsufficiency Score for ISCA-37423-Gain was changed from to None.
Source NHS GMS was added to Region: ISCA-37423-Gain.
Genetic epilepsy syndromes v1.243 ISCA-37415-Loss Rebecca Foulger Triplosensitivity Score for ISCA-37415-Loss was changed from to None.
Source NHS GMS was added to Region: ISCA-37415-Loss.
Genetic epilepsy syndromes v1.242 ISCA-37411-Loss Rebecca Foulger Triplosensitivity Score for ISCA-37411-Loss was changed from to None.
Source NHS GMS was added to Region: ISCA-37411-Loss.
Genetic epilepsy syndromes v1.241 ISCA-37404-Loss Rebecca Foulger Triplosensitivity Score for ISCA-37404-Loss was changed from to None.
Source NHS GMS was added to Region: ISCA-37404-Loss.
Genetic epilepsy syndromes v1.240 ISCA-46295-Loss Rebecca Foulger Triplosensitivity Score for ISCA-46295-Loss was changed from to None.
Source NHS GMS was added to Region: ISCA-46295-Loss.
Genetic epilepsy syndromes v1.239 ISCA-46295-Loss Rebecca Foulger commented on Region: ISCA-46295-Loss
Genetic epilepsy syndromes v1.239 ISCA-46290-Gain Rebecca Foulger commented on Region: ISCA-46290-Gain
Genetic epilepsy syndromes v1.239 ISCA-37493-Loss Rebecca Foulger reviewed Region: ISCA-37493-Loss: Rating: ; Mode of pathogenicity: None; Publications: 28283832; Phenotypes: ; Mode of inheritance: None
Genetic epilepsy syndromes v1.239 ISCA-37478-Loss Rebecca Foulger commented on Region: ISCA-37478-Loss
Genetic epilepsy syndromes v1.239 ISCA-37478-Gain Rebecca Foulger commented on Region: ISCA-37478-Gain
Genetic epilepsy syndromes v1.239 ISCA-37434-Loss Rebecca Foulger commented on Region: ISCA-37434-Loss
Genetic epilepsy syndromes v1.239 ISCA-37432-Gain Rebecca Foulger commented on Region: ISCA-37432-Gain
Genetic epilepsy syndromes v1.239 ISCA-37430-Loss Rebecca Foulger commented on Region: ISCA-37430-Loss
Genetic epilepsy syndromes v1.239 ISCA-37429-Loss Rebecca Foulger commented on Region: ISCA-37429-Loss
Genetic epilepsy syndromes v1.239 ISCA-37415-Loss Rebecca Foulger reviewed Region: ISCA-37415-Loss: Rating: ; Mode of pathogenicity: None; Publications: 10573006; Phenotypes: ; Mode of inheritance: None
Genetic epilepsy syndromes v1.239 ISCA-37423-Gain Rebecca Foulger reviewed Region: ISCA-37423-Gain: Rating: ; Mode of pathogenicity: None; Publications: 28533195; Phenotypes: ; Mode of inheritance: None
Genetic epilepsy syndromes v1.239 ISCA-37411-Loss Rebecca Foulger reviewed Region: ISCA-37411-Loss: Rating: ; Mode of pathogenicity: None; Publications: 19289393; Phenotypes: ; Mode of inheritance: None
Genetic epilepsy syndromes v1.239 ISCA-37404-Loss Rebecca Foulger commented on Region: ISCA-37404-Loss
Severe early-onset obesity v1.22 ISCA-37486-Loss Ivone Leong reviewed Region: ISCA-37486-Loss: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None; Current diagnostic: yes
Severe early-onset obesity v1.22 ISCA-37478-Loss Ivone Leong reviewed Region: ISCA-37478-Loss: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None; Current diagnostic: yes
Severe early-onset obesity v1.22 ISCA-37404-Loss Ivone Leong reviewed Region: ISCA-37404-Loss: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None; Current diagnostic: yes
Genetic epilepsy syndromes v1.239 GATM Rebecca Foulger Phenotypes for gene: GATM were changed from to Cerebral creatine deficiency syndrome 3, 612718
Genetic epilepsy syndromes v1.238 GATM Rebecca Foulger Mode of inheritance for gene: GATM was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v1.237 GATM Rebecca Foulger Publications for gene: GATM were set to
Severe early-onset obesity v1.22 KSR2 Ivone Leong reviewed gene: KSR2: Rating: RED; Mode of pathogenicity: ; Publications: 29273807; Phenotypes: ; Mode of inheritance:
Severe early-onset obesity v1.22 SH2B1 Ivone Leong reviewed gene: SH2B1: Rating: AMBER; Mode of pathogenicity: ; Publications: 28663568; Phenotypes: ; Mode of inheritance:
Severe early-onset obesity v1.22 TUB Ivone Leong reviewed gene: TUB: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe early-onset obesity v1.22 INPP5E Ivone Leong reviewed gene: INPP5E: Rating: AMBER; Mode of pathogenicity: ; Publications: 19668215, 31173343; Phenotypes: ; Mode of inheritance:
Severe early-onset obesity v1.22 GNAS Ivone Leong reviewed gene: GNAS: Rating: GREEN; Mode of pathogenicity: ; Publications: 28453643, 27991864, 28663568; Phenotypes: ; Mode of inheritance:
Severe early-onset obesity v1.22 CPE Ivone Leong reviewed gene: CPE: Rating: AMBER; Mode of pathogenicity: ; Publications: 26120850; Phenotypes: ; Mode of inheritance:
Severe early-onset obesity v1.22 CEP290 Ivone Leong reviewed gene: CEP290: Rating: AMBER; Mode of pathogenicity: ; Publications: 18327255, 23943788; Phenotypes: ; Mode of inheritance:
Severe early-onset obesity v1.22 SIM1 Ivone Leong reviewed gene: SIM1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe early-onset obesity v1.22 CEP19 Ivone Leong reviewed gene: CEP19: Rating: GREEN; Mode of pathogenicity: ; Publications: 29127258; Phenotypes: ; Mode of inheritance:
Severe early-onset obesity v1.22 NTRK2 Ivone Leong reviewed gene: NTRK2: Rating: GREEN; Mode of pathogenicity: ; Publications: 27884935, 29100083; Phenotypes: ; Mode of inheritance:
Severe early-onset obesity v1.22 WDPCP Ismaa Farooqi reviewed gene: WDPCP: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe early-onset obesity v1.22 TUB Ismaa Farooqi reviewed gene: TUB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Severe early-onset obesity v1.22 TRIM32 Ismaa Farooqi reviewed gene: TRIM32: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe early-onset obesity v1.22 PPARG Ismaa Farooqi reviewed gene: PPARG: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe early-onset obesity v1.22 NTRK2 Ismaa Farooqi reviewed gene: NTRK2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Severe early-onset obesity v1.22 NR0B2 Ismaa Farooqi reviewed gene: NR0B2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe early-onset obesity v1.22 MRAP2 Ismaa Farooqi reviewed gene: MRAP2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe early-onset obesity v1.22 MAGEL2 Ismaa Farooqi reviewed gene: MAGEL2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe early-onset obesity v1.22 KSR2 Ismaa Farooqi reviewed gene: KSR2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Severe early-onset obesity v1.22 INPP5E Ismaa Farooqi reviewed gene: INPP5E: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Severe early-onset obesity v1.22 GNAS Ismaa Farooqi reviewed gene: GNAS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed); Current diagnostic: yes
Severe early-onset obesity v1.22 CPE Ismaa Farooqi reviewed gene: CPE: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Severe early-onset obesity v1.22 CEP290 Ismaa Farooqi reviewed gene: CEP290: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Severe early-onset obesity v1.22 CEP19 Ismaa Farooqi reviewed gene: CEP19: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Severe early-onset obesity v1.22 AKR1C2 Ismaa Farooqi reviewed gene: AKR1C2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe early-onset obesity v1.22 SIM1 Ismaa Farooqi reviewed gene: SIM1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Severe early-onset obesity v1.22 SH2B1 Ismaa Farooqi reviewed gene: SH2B1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Severe early-onset obesity v1.22 VPS13B Ismaa Farooqi reviewed gene: VPS13B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Severe early-onset obesity v1.22 TTC8 Ismaa Farooqi reviewed gene: TTC8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Severe early-onset obesity v1.22 SDCCAG8 Ismaa Farooqi reviewed gene: SDCCAG8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Severe early-onset obesity v1.22 POMC Ismaa Farooqi reviewed gene: POMC: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Severe early-onset obesity v1.22 PHF6 Ismaa Farooqi reviewed gene: PHF6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Severe early-onset obesity v1.22 PCSK1 Ismaa Farooqi reviewed gene: PCSK1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Severe early-onset obesity v1.22 MYT1L Ismaa Farooqi reviewed gene: MYT1L: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Severe early-onset obesity v1.22 MKS1 Ismaa Farooqi reviewed gene: MKS1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Severe early-onset obesity v1.22 MKKS Ismaa Farooqi reviewed gene: MKKS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Severe early-onset obesity v1.22 MC4R Ismaa Farooqi reviewed gene: MC4R: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Severe early-onset obesity v1.22 LEPR Ismaa Farooqi reviewed gene: LEPR: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Severe early-onset obesity v1.22 LEP Ismaa Farooqi reviewed gene: LEP: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Severe early-onset obesity v1.22 BBS9 Ismaa Farooqi reviewed gene: BBS9: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Severe early-onset obesity v1.22 BBS7 Ismaa Farooqi reviewed gene: BBS7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Severe early-onset obesity v1.22 BBS5 Ismaa Farooqi reviewed gene: BBS5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Severe early-onset obesity v1.22 BBS4 Ismaa Farooqi reviewed gene: BBS4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Severe early-onset obesity v1.22 BBS2 Ismaa Farooqi reviewed gene: BBS2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Severe early-onset obesity v1.22 BBS12 Ismaa Farooqi reviewed gene: BBS12: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Severe early-onset obesity v1.22 BBS10 Ismaa Farooqi reviewed gene: BBS10: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Severe early-onset obesity v1.22 BBS1 Ismaa Farooqi reviewed gene: BBS1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Severe early-onset obesity v1.22 ARL6 Ismaa Farooqi reviewed gene: ARL6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Severe early-onset obesity v1.22 ALMS1 Ismaa Farooqi reviewed gene: ALMS1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes
Intellectual disability v2.1011 PUF60 Rebecca Foulger Phenotypes for gene: PUF60 were changed from Verheij syndrome, 615583; VRJS; Chromosome 8q24.3 deletion syndrome; PUF60 syndrome; Intellectual disability to Syndromic intellectual disability; Verheij syndrome, 615583; VRJS; Chromosome 8q24.3 deletion syndrome; PUF60 syndrome; Intellectual disability
Severe early-onset obesity v1.21 WDPCP Ivone Leong Source Expert list was added to WDPCP.
Mode of inheritance for gene WDPCP was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Severe early-onset obesity v1.21 TUB Ivone Leong Source Expert list was added to TUB.
Source Expert Review Amber was added to TUB.
Mode of inheritance for gene TUB was changed from to BIALLELIC, autosomal or pseudoautosomal
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Severe early-onset obesity v1.21 TRIM32 Ivone Leong Source Expert list was added to TRIM32.
Severe early-onset obesity v1.21 PPARG Ivone Leong Source Expert list was added to PPARG.
Severe early-onset obesity v1.21 NTRK2 Ivone Leong Source Expert Review Green was added to NTRK2.
Source Expert list was added to NTRK2.
Mode of inheritance for gene NTRK2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene NTRK2 were changed from 26727462 association with physical activity score; 26629410 "female Nkx2.1-Ntrk2-/- mice exhibit an increased body weight and adiposity phenotype more robust than in males, which is accompanied by hyperphagia that precedes the onset of a body weight difference"; 24950379 GWAS found signals close to this gene associated with birth weight; 16702999 functional studies; 15494731 heterozygous variant reported in a 8-year-old male with a complex developmental syndrome and severe obesity to 16702999 functional studies; 27884935; 29100083; 24950379 GWAS found signals close to this gene associated with birth weight; 26727462 association with physical activity score; 26629410 female Nkx2.1-Ntrk2-/- mice exhibit an increased body weight and adiposity phenotype more robust than in males, which is accompanied by hyperphagia that precedes the onset of a body weight difference; 15494731 heterozygous variant reported in a 8-year-old male with a complex developmental syndrome and severe obesity
Rating Changed from Red List (low evidence) to Green List (high evidence)
Severe early-onset obesity v1.21 NR0B2 Ivone Leong Source Expert list was added to NR0B2.
Severe early-onset obesity v1.21 MRAP2 Ivone Leong Source Expert list was added to MRAP2.
Severe early-onset obesity v1.21 MAGEL2 Ivone Leong Source Expert list was added to MAGEL2.
Severe early-onset obesity v1.21 KSR2 Ivone Leong Source Expert list was added to KSR2.
Publications for gene KSR2 were changed from 24209692 - Study sequenced the KSR2 gene in 1770 individuals of mixed European descent with severe, early-onset obesity (age of onset <10 years) recruited to the Genetics of Obesity Study. Compared to 1536 control individuals from a large UK population-based study ELY. They report an enrichment of loss-of-function variants in KSR2 in cases versus controls, however these did not consistently co-segregate with severe obesity and they state that other genetic and/or environmental factors may modulate the phenotype. Some variants found in severely obese individuals were found in controls, and in publicly available exome data, though the authors argue that some of the controls were overweight/obese and for publicly available databases the phenotypic information are not available in order to rule out obesity in these individuals; 18719666 - This screen identified a novel body-fat phenotypes in KSR2 Knockout mice; 27561547 - ksr2(-/-) mice are normal size at birth but show a marked increase in FGF21 accompanied by reduced body mass, shortened body length, and reduced bone mineral density (BMD) and content (BMC) first evident during postnatal development; 24997067 - Relative to wild-type mice, ksr2(-/-) mice are small prior to weaning with normal glucose tolerance at 6 weeks of age, but demonstrate excess adiposity by 9 weeks and glucose intolerance by 12-14 weeks...The phenotype of C57BL/6 ksr2(-/-) mice, including obesity and obesity-related dysregulation of glucose homeostasis, recapitulates that of humans with KSR2 mutations, demonstrating the applicability of the C57BL/6 ksr2(-/-) mouse model to the study of the pathogenesis of human disease to 29273807
Severe early-onset obesity v1.21 INPP5E Ivone Leong Source Expert list was added to INPP5E.
Source Expert Review Amber was added to INPP5E.
Mode of inheritance for gene INPP5E was changed from to BIALLELIC, autosomal or pseudoautosomal
Publications for gene INPP5E were changed from to 19668215; 31173343
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Severe early-onset obesity v1.21 GNAS Ivone Leong Source Expert Review Green was added to GNAS.
Source Expert list was added to GNAS.
Mode of inheritance for gene GNAS was changed from to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Publications for gene GNAS were changed from to 27991864; 28663568; 28453643
Rating Changed from Red List (low evidence) to Green List (high evidence)
Severe early-onset obesity v1.21 CPE Ivone Leong Source Expert Review Amber was added to CPE.
Publications for gene CPE were changed from 15358678; 15870393 to 26120850; 15870393; 15358678
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Severe early-onset obesity v1.21 CEP290 Ivone Leong Source Expert list was added to CEP290.
Source Expert Review Amber was added to CEP290.
Publications for gene CEP290 were changed from to 23943788; 18327255
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Severe early-onset obesity v1.21 CEP19 Ivone Leong Source Expert Review Green was added to CEP19.
Source Expert list was added to CEP19.
Publications for gene CEP19 were changed from 24268657 to 29127258; 24268657
Rating Changed from Red List (low evidence) to Green List (high evidence)
Severe early-onset obesity v1.21 AKR1C2 Ivone Leong Source Expert list was added to AKR1C2.
Severe early-onset obesity v1.21 SIM1 Ivone Leong Source Expert Review Green was added to SIM1.
Added phenotypes Obesity, severe, 601665; obesity; Congenital Obesity for gene: SIM1
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe early-onset obesity v1.21 SH2B1 Ivone Leong Publications for gene SH2B1 were changed from 26031769 - we performed a mutation screen for variants in the SH2B1 coding region in 581 obese children and adolescents and 433 healthy, lean individuals. Mutation analysis resulted in the identification of fifteen rare non-synonymous heterozygous variants. Several of these were found both in lean and obese subjects, suggesting that these are neutral polymorphisms. However, six private, heterozygous, non-synonymous variations were present in obese children only. Furthermore, we also identified six missense variants solely in lean individuals; 25955518 - GWAS studies have identified an association with adult BMI with a region with high linkage disequilibrium that includes five genes (SH2B1, APOBR, SULT1A1 and SULT1A2, TUFM). This study showed APOBR variants contribute as much as SH2B1 variants to the association; 26075635; 24971614 - "We describe the identification of 4 novel variants in SH2B1 that are present in individuals with obesity and insulin resistance. Some of the variants we found in severely obese individuals are also found in publicly available exomes...However, because BMI and additional phenotypic information for individuals in these datasets are not available, the precise contribution of these variants to obesity remains to be established...These findings suggest that SH2B1 contains a spectrum of common and rare alleles that contribute to BMI and obesity predisposition with a broad range of penetrance, from low to more highly penetrant rare alleles. One variant, A663V, was identified in 14 severely obese individuals in the GOOS cohort as well as in many publically available exomes. In cells, A663V affected the ability of SH2B1 to enhance cell motility in response to GH. Therefore, it is possible that this variant may contribute to the phenotype of variant carriers. These findings suggest that SH2B1 contains a spectrum of common and rare alleles that contribute to BMI and obesity predisposition with a broad range of penetrance, from low to more highly penetrant rare alleles. One variant, A663V, was identified in 14 severely obese individuals in the GOOS cohort as well as in many publically available exomes. In cells, A663V affected the ability of SH2B1 to enhance cell motility in response to GH. Therefore, it is possible that this variant may contribute to the phenotype of variant carriers."; 23160192 - "We identified 300 patients with severe early-onset obesity from the Genetics of Obesity Study (GOOS) cohort (11) with a disproportionate degree of insulin resistance for their obesity, as defined by the presence of acanthosis nigricans, development of type 2 diabetes in early adolescence, and/or markedly elevated plasma insulin (top decile for age, gender, and BMI). Mutations in the genes causing the known monogenic obesity syndromes had been excluded in these patients, as had deletions at 16p11.2 by multiplex ligation–dependent probe amplification (MLPA)." 5 unrelated probands of mixed European descent with heterozygous mutations in SH2B1 were reported to be absent from 500 control subjects. All mutations were inherited from overweight/obese parents, and carriers were hyperphagic and had reduced final height as adults. to 20808231; 24971614; 28663568; 23160192
Severe early-onset obesity v1.21 VPS13B Ivone Leong Source Expert list was added to VPS13B.
Added phenotypes Cohen syndrome, 216550 for gene: VPS13B
Severe early-onset obesity v1.21 TTC8 Ivone Leong Source Expert list was added to TTC8.
Added phenotypes Bardet-Biedl syndrome 8, 615985 for gene: TTC8
Severe early-onset obesity v1.21 SDCCAG8 Ivone Leong Source Expert list was added to SDCCAG8.
Added phenotypes Bardet-Biedl syndrome 16, 615993 for gene: SDCCAG8
Severe early-onset obesity v1.21 POMC Ivone Leong Source Expert list was added to POMC.
Added phenotypes Obesity, adrenal insufficiency, and red hair due to POMC deficiency, 609734; {Obesity, early-onset, susceptibility to}, 601665 for gene: POMC
Severe early-onset obesity v1.21 PHF6 Ivone Leong Source Expert list was added to PHF6.
Added phenotypes Borjeson-Forssman-Lehmann syndrome, 301900 for gene: PHF6
Severe early-onset obesity v1.21 PCSK1 Ivone Leong Source Expert list was added to PCSK1.
Added phenotypes Obesity with impaired prohormone processing, 600955; {Obesity, susceptibility to, BMIQ12}, 612362 for gene: PCSK1
Severe early-onset obesity v1.21 MYT1L Ivone Leong Source Expert list was added to MYT1L.
Added phenotypes Mental retardation, autosomal dominant 39, 616521 for gene: MYT1L
Severe early-onset obesity v1.21 MKS1 Ivone Leong Source Expert list was added to MKS1.
Added phenotypes Bardet-Biedl syndrome 13, 615990 for gene: MKS1
Severe early-onset obesity v1.21 MKKS Ivone Leong Source Expert list was added to MKKS.
Added phenotypes Bardet-Biedl syndrome 6, 605231 for gene: MKKS
Severe early-onset obesity v1.21 MC4R Ivone Leong Source Expert list was added to MC4R.
Added phenotypes Obesity (BMIQ20), 618406; {Obesity, resistence to (BMIQ20)}, 618306 for gene: MC4R
Severe early-onset obesity v1.21 LEPR Ivone Leong Source Expert list was added to LEPR.
Added phenotypes Obesity, morbid, due to leptin receptor deficiency, 614963 for gene: LEPR
Severe early-onset obesity v1.21 LEP Ivone Leong Source Expert list was added to LEP.
Added phenotypes Obesity, morbid, due to leptin deficiency, 614962 for gene: LEP
Severe early-onset obesity v1.21 BBS9 Ivone Leong Source Expert list was added to BBS9.
Added phenotypes Bardet-Biedl syndrome 9, 615986 for gene: BBS9
Severe early-onset obesity v1.21 BBS7 Ivone Leong Source Expert list was added to BBS7.
Added phenotypes Bardet-Biedl syndrome 7, 615984 for gene: BBS7
Severe early-onset obesity v1.21 BBS5 Ivone Leong Source Expert list was added to BBS5.
Added phenotypes Bardet-Biedl syndrome 5, 615983 for gene: BBS5
Severe early-onset obesity v1.21 BBS4 Ivone Leong Source Expert list was added to BBS4.
Added phenotypes Bardet-Biedl syndrome 4, 615982 for gene: BBS4
Severe early-onset obesity v1.21 BBS2 Ivone Leong Source Expert list was added to BBS2.
Added phenotypes Bardet-Biedl syndrome 2, 615981 for gene: BBS2
Severe early-onset obesity v1.21 BBS12 Ivone Leong Source Expert list was added to BBS12.
Added phenotypes Bardet-Biedl syndrome 12, 615989 for gene: BBS12
Severe early-onset obesity v1.21 BBS10 Ivone Leong Source Expert list was added to BBS10.
Added phenotypes Bardet-Biedl syndrome 10, 615987 for gene: BBS10
Severe early-onset obesity v1.21 BBS1 Ivone Leong Source Expert list was added to BBS1.
Added phenotypes Bardet-Biedl syndrome 1, 209900 for gene: BBS1
Severe early-onset obesity v1.21 ARL6 Ivone Leong Source Expert list was added to ARL6.
Added phenotypes Bardet-Biedl syndrome 3, 600151 for gene: ARL6
Severe early-onset obesity v1.21 ALMS1 Ivone Leong Source Expert list was added to ALMS1.
Added phenotypes Alstrom syndrome, 203800 for gene: ALMS1
Undiagnosed metabolic disorders v1.179 LIPC Sarah Leigh Publications for gene: LIPC were set to 27604308
Undiagnosed metabolic disorders v1.178 LIPC Sarah Leigh Phenotypes for gene: LIPC were changed from Hepatic lipase deficiency (Inherited mixed hyperlipidaemias); Hepatic lipase deficiency, 614025; [High density lipoprotein cholesterol level QTL 12] 612797; {Diabetes mellitus, noninsulin-dependent} 125853 to {Diabetes mellitus, noninsulin-dependent} 125853; Hepatic lipase deficiency 614025; [High density lipoprotein cholesterol level QTL 12] 612797
Inborn errors of metabolism v1.168 LIPC Sarah Leigh Phenotypes for gene: LIPC were changed from {Diabetes mellitus, noninsulin-dependent} 125853; Hepatic lipase deficiency (Inherited mixed hyperlipidaemias); Hepatic lipase deficiency, 614025; [High density lipoprotein cholesterol level QTL 12] 612797 to {Diabetes mellitus, noninsulin-dependent} 125853; Hepatic lipase deficiency 614025; [High density lipoprotein cholesterol level QTL 12] 612797
Inborn errors of metabolism v1.167 LDLRAP1 Sarah Leigh Classified gene: LDLRAP1 as Green List (high evidence)
Inborn errors of metabolism v1.167 LDLRAP1 Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 11 variants reported.
Inborn errors of metabolism v1.167 LDLRAP1 Sarah Leigh Gene: ldlrap1 has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.177 LDLRAP1 Sarah Leigh Classified gene: LDLRAP1 as Green List (high evidence)
Undiagnosed metabolic disorders v1.177 LDLRAP1 Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 11 variants reported.
Undiagnosed metabolic disorders v1.177 LDLRAP1 Sarah Leigh Gene: ldlrap1 has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.166 LDLRAP1 Sarah Leigh Publications for gene: LDLRAP1 were set to 27604308
Undiagnosed metabolic disorders v1.176 LDLRAP1 Sarah Leigh Publications for gene: LDLRAP1 were set to 27604308
Severe early-onset obesity v1.20 ISCA-37404-Loss Ivone Leong Triplosensitivity Score for ISCA-37404-Loss was changed from to None.
Source Expert list was added to Region: ISCA-37404-Loss.
Severe early-onset obesity v1.19 ISCA-37486-Loss Ivone Leong Triplosensitivity Score for ISCA-37486-Loss was changed from to None.
Source Expert list was added to Region: ISCA-37486-Loss.
Severe early-onset obesity v1.18 ISCA-37478-Loss Ivone Leong Triplosensitivity Score for ISCA-37478-Loss was changed from to None.
Source Expert list was added to Region: ISCA-37478-Loss.
Inborn errors of metabolism v1.165 LDLRAP1 Sarah Leigh Added comment: Comment on phenotypes: Familial hypercholesterolaemia;Autosomal recessive hypercholesterolemia (Inherited hypercholesterolaemias)
Inborn errors of metabolism v1.165 LDLRAP1 Sarah Leigh Phenotypes for gene: LDLRAP1 were changed from Familial hypercholesterolaemia; Autosomal recessive hypercholesterolemia (Inherited hypercholesterolaemias) to Hypercholesterolemia, familial, 4 603813
Undiagnosed metabolic disorders v1.175 LDLRAP1 Sarah Leigh Added comment: Comment on phenotypes: Autosomal recessive hypercholesterolemia (Inherited hypercholesterolaemias);Familial hypercholesterolaemia
Undiagnosed metabolic disorders v1.175 LDLRAP1 Sarah Leigh Phenotypes for gene: LDLRAP1 were changed from Autosomal recessive hypercholesterolemia (Inherited hypercholesterolaemias); Familial hypercholesterolaemia to Hypercholesterolemia, familial, 4 603813
Intellectual disability v2.1010 COLEC10 Rebecca Foulger commented on gene: COLEC10
Inborn errors of metabolism v1.164 LDLR Sarah Leigh Publications for gene: LDLR were set to 27604308; 27821657
Undiagnosed metabolic disorders v1.174 LDLR Sarah Leigh Publications for gene: LDLR were set to 27604308; 27821657
Intellectual disability v2.1010 COLEC10 Rebecca Foulger Phenotypes for gene: COLEC10 were changed from to 3MC syndrome 3, 248340
Intellectual disability v2.1009 COLEC10 Rebecca Foulger Publications for gene: COLEC10 were set to
Undiagnosed metabolic disorders v1.173 LDLR Sarah Leigh Classified gene: LDLR as Green List (high evidence)
Undiagnosed metabolic disorders v1.173 LDLR Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. Over 2000 variants reported.
Undiagnosed metabolic disorders v1.173 LDLR Sarah Leigh Gene: ldlr has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.172 LDLR Sarah Leigh Publications for gene: LDLR were set to 27604308
Inborn errors of metabolism v1.163 LDLR Sarah Leigh Publications for gene: LDLR were set to 27604308
Primary immunodeficiency v1.42 PSMB4 Louise Daugherty Deleted their comment
Inborn errors of metabolism v1.162 LDLR Sarah Leigh Classified gene: LDLR as Green List (high evidence)
Inborn errors of metabolism v1.162 LDLR Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. Over 2000 variants reported.
Inborn errors of metabolism v1.162 LDLR Sarah Leigh Gene: ldlr has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.161 LDLR Sarah Leigh Added comment: Comment on phenotypes: Familial hypercholesterolaemia;Disorder of low density lipoprotein receptor (Inherited hypercholesterolaemias)
Inborn errors of metabolism v1.161 LDLR Sarah Leigh Phenotypes for gene: LDLR were changed from Familial hypercholesterolaemia; Disorder of low density lipoprotein receptor (Inherited hypercholesterolaemias) to Hypercholesterolemia, familial, 1 143890; LDL cholesterol level QTL2 143890
Undiagnosed metabolic disorders v1.171 LDLR Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.171 LDLR Sarah Leigh Added comment: Comment on phenotypes: Disorder of low density lipoprotein receptor (Inherited hypercholesterolaemias);Familial hypercholesterolaemia
Undiagnosed metabolic disorders v1.171 LDLR Sarah Leigh Phenotypes for gene: LDLR were changed from Disorder of low density lipoprotein receptor (Inherited hypercholesterolaemias); Familial hypercholesterolaemia to Hypercholesterolemia, familial, 1 143890; LDL cholesterol level QTL2 143890
Intellectual disability v2.1008 FRMPD4 Rebecca Foulger Classified gene: FRMPD4 as Green List (high evidence)
Intellectual disability v2.1008 FRMPD4 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green on advice of Genomics England clinical team: four families with a relevant phenotype meets the criteria for a Green rating.
Intellectual disability v2.1008 FRMPD4 Rebecca Foulger Gene: frmpd4 has been classified as Green List (High Evidence).
Intellectual disability v2.1007 FRMPD4 Rebecca Foulger Added comment: Comment on mode of inheritance: MOI set to X-linked dominant on advice of Genomics England clinical team, in view of the single reported female heterozygote with a relevant phenotype.
Intellectual disability v2.1007 FRMPD4 Rebecca Foulger Mode of inheritance for gene: FRMPD4 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, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Undiagnosed metabolic disorders v1.170 LBR Sarah Leigh Publications for gene: LBR were set to 27604308
Inborn errors of metabolism v1.160 LBR Sarah Leigh Classified gene: LBR as Green List (high evidence)
Inborn errors of metabolism v1.160 LBR Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene for Greenberg skeletal dysplasia 215140. At least 15 variants have been reported, in 5 unrelated cases of Pelger-Huet anomaly 169400, 3 unrelated cases of Pelger-Huet anomaly with mild skeletal anomalies 618019, 5 unrelated cases of Greenberg skeletal dysplasia 215140 and in a single case of ?Reynolds syndrome 613471.
Inborn errors of metabolism v1.160 LBR Sarah Leigh Gene: lbr has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.169 LBR Sarah Leigh Classified gene: LBR as Green List (high evidence)
Undiagnosed metabolic disorders v1.169 LBR Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene for Greenberg skeletal dysplasia 215140. At least 15 variants have been reported, in 5 unrelated cases of Pelger-Huet anomaly 169400, 3 unrelated cases of Pelger-Huet anomaly with mild skeletal anomalies 618019, 5 unrelated cases of Greenberg skeletal dysplasia 215140 and in a single case of ?Reynolds syndrome 613471.
Undiagnosed metabolic disorders v1.169 LBR Sarah Leigh Gene: lbr has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.168 LBR Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.168 LBR Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.168 LBR Sarah Leigh Deleted their comment
Inborn errors of metabolism v1.159 LBR Sarah Leigh Publications for gene: LBR were set to 27604308
Intellectual disability v2.1006 GRIA2 Rebecca Foulger commented on gene: GRIA2
Limb disorders v1.57 LBR Eleanor Williams Added comment: Comment on mode of inheritance: Appears to be Biallelic in Greenberg dysplasia and in Pelger-Huet anomaly with skeletal anomalies. (Pelger-Huet anomaly without skeletal involvement can be monoallelic)
Limb disorders v1.57 LBR Eleanor Williams Mode of inheritance for gene: LBR was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Skeletal ciliopathies v0.13 LBR Eleanor Williams Added comment: Comment on mode of inheritance: Appears to be Biallelic in Greenberg dysplasia and in Pelger-Huet anomaly with skeletal anomalies. (Pelger-Huet anomaly without skeletal involvement can be monoallelic)
Skeletal ciliopathies v0.13 LBR Eleanor Williams Mode of inheritance for gene: LBR was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.193 LBR Eleanor Williams Added comment: Comment on mode of inheritance: Appears to be Biallelic in Greenberg dysplasia and in Pelger-Huet anomaly with skeletal anomalies. (Pelger-Huet anomaly without skeletal involvement can be monoallelic)
Skeletal dysplasia v1.193 LBR Eleanor Williams Mode of inheritance for gene: LBR was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v2.1006 POLR2A Rebecca Foulger Classified gene: POLR2A as Green List (high evidence)
Intellectual disability v2.1006 POLR2A Rebecca Foulger Gene: polr2a has been classified as Green List (High Evidence).
Intellectual disability v2.1005 POLR2A Rebecca Foulger Phenotypes for gene: POLR2A were changed from Generalized hypotonia; Global developmental delay; Feeding difficulties to Global developmental delay; Generalized hypotonia; Feeding difficulties
Intellectual disability v2.1004 POLR2A Rebecca Foulger commented on gene: POLR2A
Intellectual disability v2.1004 AFF3 Rebecca Foulger changed review comment from: As noted by Konstantinos Varvagiannis, Voisin et al., 2019 (not yet in PubMed) describe de novo missense variants in the degron of AFF3 (a region required for its degradation) in 10 unrelated individuals with symptoms including ID. 4 different missense variants were identified (p.A258S, p.A258T, p.A258V and p.V260G). Although there are sufficient cases with a relevant phenotype, I have rated as Amber pending publication of the 2019 article: as OMIM note in their correspondance on AFF3, information changes from the initial bioRxiv upload to peer-reviewed publication. Therefore updated rating of AFF3 from Red to Amber, added 'watchlist' tag (in addition to missense tag), and will re-curate when the paper is published.; to: As noted by Konstantinos Varvagiannis, Voisin et al., 2019 (not yet in PubMed) describe de novo missense variants in the degron of AFF3 (a region required for its degradation) in 10 unrelated individuals with symptoms including ID. 4 different missense variants were identified (p.A258S, p.A258T, p.A258V and p.V260G). Although there are sufficient cases with a relevant phenotype (plus the individual reported in PMID:18616733), I have rated as Amber pending publication of the Voisin 2019 article: as OMIM note in their correspondance on AFF3, information changes from the initial bioRxiv upload to peer-reviewed publication. Therefore updated rating of AFF3 from Red to Amber, added 'watchlist' tag and 'missense' tag, and will re-curate when the paper is published.
Intellectual disability v2.1004 AFF3 Rebecca Foulger Publications for gene: AFF3 were set to
Intellectual disability v2.1003 AFF3 Rebecca Foulger Phenotypes for gene: AFF3 were changed from to Intellectual disability; Seizures
Intellectual disability v2.1002 AFF3 Rebecca Foulger Mode of inheritance for gene: AFF3 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v2.1001 AFF3 Rebecca Foulger Mode of pathogenicity for gene: AFF3 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Undiagnosed metabolic disorders v1.168 LBR Sarah Leigh Added comment: Comment on phenotypes: Greenberg skeletal dysplasia (Disorders of sterol biosynthesis);Fetal hydrops;Unexplained skeletal dysplasia
Undiagnosed metabolic disorders v1.168 LBR Sarah Leigh Phenotypes for gene: LBR were changed from Greenberg skeletal dysplasia (Disorders of sterol biosynthesis); Fetal hydrops; Unexplained skeletal dysplasia to ?Reynolds syndrome 613471; Greenberg skeletal dysplasia 215140; Pelger-Huet anomaly 169400; Pelger-Huet anomaly with mild skeletal anomalies 618019
Inborn errors of metabolism v1.158 LBR Sarah Leigh Added comment: Comment on phenotypes: Greenberg skeletal dysplasia (Disorders of sterol biosynthesis);Unexplained skeletal dysplasia;Fetal hydrops
Inborn errors of metabolism v1.158 LBR Sarah Leigh Phenotypes for gene: LBR were changed from Greenberg skeletal dysplasia (Disorders of sterol biosynthesis); Unexplained skeletal dysplasia; Fetal hydrops to ?Reynolds syndrome 613471; Greenberg skeletal dysplasia 215140; Pelger-Huet anomaly 169400; Pelger-Huet anomaly with mild skeletal anomalies 618019
Intellectual disability v2.1001 AFF3 Rebecca Foulger Classified gene: AFF3 as Amber List (moderate evidence)
Intellectual disability v2.1001 AFF3 Rebecca Foulger Gene: aff3 has been classified as Amber List (Moderate Evidence).
Intellectual disability v2.1000 AFF3 Rebecca Foulger Tag watchlist tag was added to gene: AFF3.
Intellectual disability v2.1000 AFF3 Rebecca Foulger Tag missense tag was added to gene: AFF3.
Intellectual disability v2.1000 AFF3 Rebecca Foulger commented on gene: AFF3
Undiagnosed metabolic disorders v1.167 ISCU Sarah Leigh Classified gene: ISCU as Green List (high evidence)
Undiagnosed metabolic disorders v1.167 ISCU Sarah Leigh Added comment: Comment on list classification: Sufficient published reported biallelic cases, with supportive functional studies. The most frequent reported variant c.343+382G>C g.108567650G>C is deep in intron five of the gene and strengthens a weak splicing acceptor site, with consequent retention of a 100-bp intronic sequence upstream of the known terminal exon, introduction of a stop codon and decreased levels of ISCU mRNA and protein (PMID 18304497). This may be missed by standard sequencing.
Undiagnosed metabolic disorders v1.167 ISCU Sarah Leigh Gene: iscu has been classified as Green List (High Evidence).
Cardiomyopathies - including childhood onset v1.34 ISCU Sarah Leigh Tag non-coding-known-pathogenic tag was added to gene: ISCU.
Molecular autopsy v0.99 ISCU Sarah Leigh Tag non-coding-known-pathogenic tag was added to gene: ISCU.
Inborn errors of metabolism v1.157 ISCU Sarah Leigh Tag non-coding-known-pathogenic tag was added to gene: ISCU.
Undiagnosed metabolic disorders v1.166 ISCU Sarah Leigh Tag non-coding-known-pathogenic tag was added to gene: ISCU.
Inborn errors of metabolism v1.157 ISCU Sarah Leigh Publications for gene: ISCU were set to 18304497; 29079705; 18296749; 19567699; 20206689
Intellectual disability v2.1000 WDR37 Rebecca Foulger commented on gene: WDR37: Added missense tag: only missense variants reported so far (PMID:31327510 and PMID:31327508).
Undiagnosed metabolic disorders v1.166 ISCU Sarah Leigh Publications for gene: ISCU were set to 27604308
Undiagnosed metabolic disorders v1.165 ISCU Sarah Leigh Deleted their comment
Inborn errors of metabolism v1.156 ISCU Sarah Leigh commented on gene: ISCU: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Inborn errors of metabolism v1.156 HSD17B10 Sarah Leigh Classified gene: HSD17B10 as Green List (high evidence)
Inborn errors of metabolism v1.156 HSD17B10 Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene for 2-methyl-3-hydroxybutyrylL-coA dehydrogenase deficiency and for mental retardation syndromic X-linked type 10 . At least 8 variants reported.
Inborn errors of metabolism v1.156 HSD17B10 Sarah Leigh Gene: hsd17b10 has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.165 HSD17B10 Sarah Leigh Classified gene: HSD17B10 as Green List (high evidence)
Undiagnosed metabolic disorders v1.165 HSD17B10 Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene for 2-methyl-3-hydroxybutyrylL-coA dehydrogenase deficiency and for mental retardation syndromic X-linked type 10 . At least 8 variants reported.
Undiagnosed metabolic disorders v1.165 HSD17B10 Sarah Leigh Gene: hsd17b10 has been classified as Green List (High Evidence).
Intellectual disability v2.1000 WDR37 Rebecca Foulger Classified gene: WDR37 as Green List (high evidence)
Intellectual disability v2.1000 WDR37 Rebecca Foulger Gene: wdr37 has been classified as Green List (High Evidence).
Intellectual disability v2.1000 WDR37 Rebecca Foulger Mode of pathogenicity for gene: WDR37 was changed from None to Other
Intellectual disability v2.999 WDR37 Rebecca Foulger commented on gene: WDR37: WDR37 was added to the ID panel and rated Green by Konstantinos Varvagiannis. Although WDR37 is not yet associated with a disorder in OMIM or Gene2Phenotype, there are sufficient unrelated cases in two recent papers (PMID:31327510 and PMID:31327508) with a severe ID/DD phenotype for inclusion on the panel. Plus it was agreed at the Webex call on Thurs 8th August with members of the GMS Neurology Specialist Test Group that WDR37 should be rated Green on the epilepsy panel (402). Therefore updated rating from Grey to Green.
Inborn errors of metabolism v1.155 HSD17B10 Sarah Leigh Publications for gene: HSD17B10 were set to 19706438; 22132097; 12696021; 26950678
Undiagnosed metabolic disorders v1.164 HSD17B10 Sarah Leigh Publications for gene: HSD17B10 were set to 27604308
Inborn errors of metabolism v1.154 HSD17B10 Sarah Leigh Added comment: Comment on phenotypes: Intellectual disability;2-Methyl-3-hydroxybutyric aciduria, HSD10 disease (Organic acidurias);Intellectual_disability;HSD10 mitochondrial disease 300438
Inborn errors of metabolism v1.154 HSD17B10 Sarah Leigh Phenotypes for gene: HSD17B10 were changed from Intellectual disability; 2-Methyl-3-hydroxybutyric aciduria, HSD10 disease (Organic acidurias); Intellectual_disability; HSD10 mitochondrial disease 300438 to HSD10 mitochondrial disease 300438
Undiagnosed metabolic disorders v1.163 HSD17B10 Sarah Leigh Added comment: Comment on phenotypes: 2-Methyl-3-hydroxybutyric aciduria, HSD10 disease (Organic acidurias);Intellectual disability;Intellectual_disability
Undiagnosed metabolic disorders v1.163 HSD17B10 Sarah Leigh Phenotypes for gene: HSD17B10 were changed from 2-Methyl-3-hydroxybutyric aciduria, HSD10 disease (Organic acidurias); Intellectual disability; Intellectual_disability to HSD10 mitochondrial disease 300438
Undiagnosed metabolic disorders v1.162 HSD17B10 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.162 HSD17B10 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.162 HSD17B10 Sarah Leigh Deleted their comment
Intellectual disability v2.999 WDR37 Rebecca Foulger Tag missense tag was added to gene: WDR37.
Intellectual disability v2.999 WDR37 Rebecca Foulger commented on gene: WDR37
Inborn errors of metabolism v1.153 HPS1 Sarah Leigh Added comment: Comment on phenotypes: Infantile enterocolitis & monogenic inflammatory bowel disease;Hermansky-Pudlak Syndrome (Other lysosomal disorders);Inherited bleeding disorders
Inborn errors of metabolism v1.153 HPS1 Sarah Leigh Phenotypes for gene: HPS1 were changed from Infantile enterocolitis & monogenic inflammatory bowel disease; Hermansky-Pudlak Syndrome (Other lysosomal disorders); Inherited bleeding disorders to Hermansky-Pudlak syndrome 1 203300
Undiagnosed metabolic disorders v1.162 HPS1 Sarah Leigh Publications for gene: HPS1 were set to 27604308
Inborn errors of metabolism v1.152 HPS1 Sarah Leigh Publications for gene: HPS1 were set to 27604308
Inborn errors of metabolism v1.151 HPS1 Sarah Leigh Classified gene: HPS1 as Green List (high evidence)
Inborn errors of metabolism v1.151 HPS1 Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 7 variants reported in at least 5 unrelated cases.
Inborn errors of metabolism v1.151 HPS1 Sarah Leigh Gene: hps1 has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.161 HPS1 Sarah Leigh Classified gene: HPS1 as Green List (high evidence)
Undiagnosed metabolic disorders v1.161 HPS1 Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 7 variants reported in at least 5 unrelated cases.
Undiagnosed metabolic disorders v1.161 HPS1 Sarah Leigh Gene: hps1 has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.160 HPS1 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.160 HPS1 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.160 HPS1 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.160 HPS1 Sarah Leigh Added comment: Comment on phenotypes: Hermansky-Pudlak Syndrome (Other lysosomal disorders);Infantile enterocolitis & monogenic inflammatory bowel disease;Inherited bleeding disorders
Undiagnosed metabolic disorders v1.160 HPS1 Sarah Leigh Phenotypes for gene: HPS1 were changed from Hermansky-Pudlak Syndrome (Other lysosomal disorders); Infantile enterocolitis & monogenic inflammatory bowel disease; Inherited bleeding disorders to Hermansky-Pudlak syndrome 1 203300
Inborn errors of metabolism v1.150 HPD Sarah Leigh Publications for gene: HPD were set to 27604308; 10942115; 11073718; 26226126; 30984715; 17560158
Inborn errors of metabolism v1.150 HPD Sarah Leigh Publications for gene: HPD were set to 27604308; 10942115; 11073718; 26226126; 30984715; 17560158
Inborn errors of metabolism v1.149 HPD Sarah Leigh Publications for gene: HPD were set to 27604308; 10942115; 11073718; 26226126:30984715; 17560158
Undiagnosed metabolic disorders v1.159 HPD Sarah Leigh Publications for gene: HPD were set to 27604308; 10942115; 11073718; 26226126:30984715; 17560158
Inborn errors of metabolism v1.149 HPD Sarah Leigh Classified gene: HPD as Green List (high evidence)
Inborn errors of metabolism v1.149 HPD Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM and as probable Gen2Phen gene for both phenotypes. At least 4 variants reported in unrelated cases of Tyrosinemia, type III 276710 and 4 variants in 6 unrelated cases of Hawkinsinuria 140350 (at least 2 of these cases were compound heterozygotes).
Inborn errors of metabolism v1.149 HPD Sarah Leigh Gene: hpd has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.158 HPD Sarah Leigh Classified gene: HPD as Green List (high evidence)
Undiagnosed metabolic disorders v1.158 HPD Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene for both phenotypes. At least 4 variants reported in unrelated cases of Tyrosinemia, type III 276710 and 4 variants in 6 unrelated cases of Hawkinsinuria 140350 (at least 2 of these cases were compound heterozygotes).
Undiagnosed metabolic disorders v1.158 HPD Sarah Leigh Gene: hpd has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.148 HPD Sarah Leigh Publications for gene: HPD were set to 27604308
Undiagnosed metabolic disorders v1.157 HPD Sarah Leigh Publications for gene: HPD were set to 27604308
Inborn errors of metabolism v1.147 HPD Sarah Leigh Deleted their comment
Proteinuric renal disease v1.222 Eleanor Williams List of related panels changed from to R195
Undiagnosed metabolic disorders v1.156 HPD Sarah Leigh Added comment: Comment on phenotypes: 4-hydroxyphenylpyruvate dioxygenase deficiency (Disorders of phenylalanine or tyrosine metabolism);Intellectual disability
Undiagnosed metabolic disorders v1.156 HPD Sarah Leigh Phenotypes for gene: HPD were changed from 4-hydroxyphenylpyruvate dioxygenase deficiency (Disorders of phenylalanine or tyrosine metabolism); Intellectual disability to Hawkinsinuria 140350; Tyrosinemia, type III 276710
Inborn errors of metabolism v1.147 HPD Sarah Leigh Added comment: Comment on phenotypes: Intellectual disability;4-hydroxyphenylpyruvate dioxygenase deficiency (Disorders of phenylalanine or tyrosine metabolism)
Inborn errors of metabolism v1.147 HPD Sarah Leigh Phenotypes for gene: HPD were changed from Hawkinsinuria 140350; Tyrosinemia, type III 276710 to Hawkinsinuria 140350; Tyrosinemia, type III 276710
Inborn errors of metabolism v1.147 HPD Sarah Leigh Added comment: Comment on phenotypes: Intellectual disability;4-hydroxyphenylpyruvate dioxygenase deficiency (Disorders of phenylalanine or tyrosine metabolism)
Inborn errors of metabolism v1.147 HPD Sarah Leigh Phenotypes for gene: HPD were changed from Intellectual disability; 4-hydroxyphenylpyruvate dioxygenase deficiency (Disorders of phenylalanine or tyrosine metabolism) to Hawkinsinuria 140350; Tyrosinemia, type III 276710
Undiagnosed metabolic disorders v1.155 HPD Sarah Leigh Deleted their comment
Inborn errors of metabolism v1.146 HADH Sarah Leigh Classified gene: HADH as Green List (high evidence)
Inborn errors of metabolism v1.146 HADH Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. Numerous variants reported in unrelated cases of Hyperinsulinemic hypoglycemia, familial, 4 609975.
Inborn errors of metabolism v1.146 HADH Sarah Leigh Gene: hadh has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.155 HADH Sarah Leigh Classified gene: HADH as Green List (high evidence)
Undiagnosed metabolic disorders v1.155 HADH Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. Numerous variants reported in unrelated cases of Hyperinsulinemic hypoglycemia, familial, 4 609975.
Undiagnosed metabolic disorders v1.155 HADH Sarah Leigh Gene: hadh has been classified as Green List (High Evidence).
Tubulointerstitial kidney disease v0.15 Eleanor Williams List of related panels changed from to R202
Inborn errors of metabolism v1.145 HADH Sarah Leigh Publications for gene: HADH were set to 27604308
Undiagnosed metabolic disorders v1.154 HADH Sarah Leigh Publications for gene: HADH were set to 27604308
Membranoproliferative glomerulonephritis v1.16 Eleanor Williams List of related panels changed from PMG; MPGN; Primary Membranoproliferative Glomerulonephritis to PMG; MPGN; Primary Membranoproliferative Glomerulonephritis; R197
Genetic epilepsy syndromes v1.236 SETD5 Rebecca Foulger changed review comment from: Re-reviewed this gene when curating panel for GMS Clinical Indication R59 Early onset or syndromic epilepsy. Although four reviewers agreed it should be on EE panel, there is limited evidence of a seizure phenotype. PMID:26482601: (Kobayashi et al., 2016) examined 11 patients with early-onset epileptic encephalopathy, and SETD5 variants were amongst the findings. Therefore awaited clinical input on whether SETD5 should be demoted on this panel.; to: Re-reviewed this gene when curating panel for GMS Clinical Indication R59 Early onset or syndromic epilepsy. In summary: although four reviewers agreed it should be on EE panel, there is limited evidence of a seizure phenotype. PMID:26482601: (Kobayashi et al., 2016) examined 11 patients with early-onset epileptic encephalopathy, and SETD5 variants were amongst the findings. Therefore consider demoting SETD5.
Genetic epilepsy syndromes v1.236 LYST Rebecca Foulger changed review comment from: Re-reviewed this gene when curating panel for GMS Clinical Indication R59 Early onset or syndromic epilepsy. Although the mouse model displays seizures (PMID:16518687), there is limited evidence of patients with seizures (no mention of seizures in PMID:9215679, and one 1990 report of Chédiak-Higashi syndrome with seizures from PMID:10450360). Therefore awaiting clinical opinion on whether LYST should be demoted on this panel.; to: Re-reviewed this gene when curating panel for GMS Clinical Indication R59 Early onset or syndromic epilepsy. In summary: although the mouse model displays seizures (PMID:16518687), there is limited evidence of patients with seizures (no mention of seizures in PMID:9215679, and one 1990 report of Chédiak-Higashi syndrome with seizures from PMID:10450360). Therefore consider demoting LYST.
Genetic epilepsy syndromes v1.236 KIF1BP Rebecca Foulger changed review comment from: Re-reviewed this gene when curating panel for GMS Clinical Indication R59 Early onset or syndromic epilepsy. Although the association with GOLDBERG-SHPRINTZEN MEGACOLON SYNDROME is strong, there is little direct evidence for seizures (PMID:28277559 identifies one case). Therefore awaiting clinical opinion on whether KIF1BP should be demoted.; to: Re-reviewed this gene when curating panel for GMS Clinical Indication R59 Early onset or syndromic epilepsy. In summary: although the association with GOLDBERG-SHPRINTZEN MEGACOLON SYNDROME is strong, there is little direct evidence for seizures (PMID:28277559 identifies one case). Therefore consider demoting KIF1BP.
Genetic epilepsy syndromes v1.236 AKT1 Rebecca Foulger Marked gene: AKT1 as ready
Genetic epilepsy syndromes v1.236 AKT1 Rebecca Foulger Gene: akt1 has been classified as Red List (Low Evidence).
Genetic epilepsy syndromes v1.236 PTEN Rebecca Foulger Marked gene: PTEN as ready
Genetic epilepsy syndromes v1.236 PTEN Rebecca Foulger Gene: pten has been classified as Red List (Low Evidence).
Genetic epilepsy syndromes v1.236 PIK3CA Rebecca Foulger Marked gene: PIK3CA as ready
Genetic epilepsy syndromes v1.236 PIK3CA Rebecca Foulger Gene: pik3ca has been classified as Red List (Low Evidence).
Genetic epilepsy syndromes v1.236 PIK3CA Rebecca Foulger Classified gene: PIK3CA as Red List (low evidence)
Genetic epilepsy syndromes v1.236 PIK3CA Rebecca Foulger Gene: pik3ca has been classified as Red List (Low Evidence).
Genetic epilepsy syndromes v1.235 PIK3CA Rebecca Foulger commented on gene: PIK3CA: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed to demote PIK3CA from Green to Red. This panel is not the appropriate test for somatic variant detection due to the coverage. R110 Segmental overgrowth disorders (panel #98) should be used where megalencephaly is present to allow detection of somatic mosaic mutations.
Genetic epilepsy syndromes v1.235 PTEN Rebecca Foulger commented on gene: PTEN: Added tags: 'mosaicism' and 'somatic'.
Genetic epilepsy syndromes v1.235 PTEN Rebecca Foulger Classified gene: PTEN as Red List (low evidence)
Genetic epilepsy syndromes v1.235 PTEN Rebecca Foulger Gene: pten has been classified as Red List (Low Evidence).
Genetic epilepsy syndromes v1.234 PTEN Rebecca Foulger commented on gene: PTEN: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed to demote AKT1 from Green to Red. This panel is not the appropriate test for somatic variant detection due to the coverage. R110 Segmental overgrowth disorders (panel #98) should be used where megalencephaly is present to allow detection of somatic mosaic mutations.
Genetic epilepsy syndromes v1.234 PTEN Rebecca Foulger Tag mosaicism tag was added to gene: PTEN.
Tag somatic tag was added to gene: PTEN.
Haematuria v1.30 Eleanor Williams List of related panels changed from Alport syndrome; Familial haematuria to Alport syndrome; Familial haematuria; R194
Genetic epilepsy syndromes v1.234 AKT1 Rebecca Foulger Classified gene: AKT1 as Red List (low evidence)
Genetic epilepsy syndromes v1.234 AKT1 Rebecca Foulger Gene: akt1 has been classified as Red List (Low Evidence).
Genetic epilepsy syndromes v1.233 AKT1 Rebecca Foulger commented on gene: AKT1: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed to demote AKT1 from Green to Red. This panel is not the appropriate test for somatic variant detection due to the coverage. R110 Segmental overgrowth disorders (panel #98) should be used where megalencephaly is present to allow detection of somatic mosaic mutations.
Genetic epilepsy syndromes v1.233 WDR37 Rebecca Foulger Marked gene: WDR37 as ready
Genetic epilepsy syndromes v1.233 WDR37 Rebecca Foulger Gene: wdr37 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v1.233 PEX5 Rebecca Foulger Marked gene: PEX5 as ready
Genetic epilepsy syndromes v1.233 PEX5 Rebecca Foulger Gene: pex5 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v1.233 KIAA1109 Rebecca Foulger Marked gene: KIAA1109 as ready
Genetic epilepsy syndromes v1.233 KIAA1109 Rebecca Foulger Gene: kiaa1109 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v1.233 GTPBP3 Rebecca Foulger Marked gene: GTPBP3 as ready
Genetic epilepsy syndromes v1.233 GTPBP3 Rebecca Foulger Gene: gtpbp3 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v1.233 EIF2B3 Rebecca Foulger Marked gene: EIF2B3 as ready
Genetic epilepsy syndromes v1.233 EIF2B3 Rebecca Foulger Gene: eif2b3 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v1.233 EIF2B1 Rebecca Foulger Marked gene: EIF2B1 as ready
Genetic epilepsy syndromes v1.233 EIF2B1 Rebecca Foulger Gene: eif2b1 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v1.233 EFHC1 Rebecca Foulger Marked gene: EFHC1 as ready
Genetic epilepsy syndromes v1.233 EFHC1 Rebecca Foulger Gene: efhc1 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v1.233 DPM2 Rebecca Foulger Marked gene: DPM2 as ready
Genetic epilepsy syndromes v1.233 DPM2 Rebecca Foulger Gene: dpm2 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v1.233 CUL4B Rebecca Foulger Marked gene: CUL4B as ready
Genetic epilepsy syndromes v1.233 CUL4B Rebecca Foulger Gene: cul4b has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v1.233 CNPY3 Rebecca Foulger Marked gene: CNPY3 as ready
Genetic epilepsy syndromes v1.233 CNPY3 Rebecca Foulger Gene: cnpy3 has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.153 HADH Sarah Leigh Added comment: Comment on phenotypes: 3-alpha-hydroxyacyl- CoA dehydrogenase deficiency (Disorders of mitochondrial fatty acid oxidation);Hyperinsulinism;Intellectual disability
Undiagnosed metabolic disorders v1.153 HADH Sarah Leigh Phenotypes for gene: HADH were changed from 3-alpha-hydroxyacyl- CoA dehydrogenase deficiency (Disorders of mitochondrial fatty acid oxidation); Hyperinsulinism; Intellectual disability to 3-hydroxyacyl-CoA dehydrogenase deficiency 231530; Hyperinsulinemic hypoglycemia, familial, 4 609975
Inborn errors of metabolism v1.144 HADH Sarah Leigh Added comment: Comment on phenotypes: Intellectual disability;Hyperinsulinism;3-alpha-hydroxyacyl- CoA dehydrogenase deficiency (Disorders of mitochondrial fatty acid oxidation)
Inborn errors of metabolism v1.144 HADH Sarah Leigh Phenotypes for gene: HADH were changed from Intellectual disability; Hyperinsulinism; 3-alpha-hydroxyacyl- CoA dehydrogenase deficiency (Disorders of mitochondrial fatty acid oxidation) to 3-hydroxyacyl-CoA dehydrogenase deficiency 231530; Hyperinsulinemic hypoglycemia, familial, 4 609975
Genetic epilepsy syndromes v1.233 PTS Rebecca Foulger Marked gene: PTS as ready
Genetic epilepsy syndromes v1.233 PTS Rebecca Foulger Gene: pts has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v1.233 PTS Rebecca Foulger Classified gene: PTS as Amber List (moderate evidence)
Genetic epilepsy syndromes v1.233 PTS Rebecca Foulger Gene: pts has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v1.232 PTS Rebecca Foulger commented on gene: PTS: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that this gene should be rated Amber to match the rating on the 'Inborn errors of metabolism' panel. The prevailing phenotype is a movement disorder. Demoted from Green to Amber.
Atypical haemolytic uraemic syndrome v1.21 Eleanor Williams List of related panels changed from to R201
Genetic epilepsy syndromes v1.232 PTS Rebecca Foulger commented on gene: PTS: Re-reviewed this gene when curating panel for GMS Clinical Indication R59 Early onset or syndromic epilepsy. In summary: Severe Hyperphenylalaninemia, BH4-deficient, is accepted to include seizures (PMID:8801112). Because this condition is diagnosed and treated from an early age, seizures may not be reported frequently. PMID:31000854 (Ahmed et al., 2019)assessed hyperphenylalaninemia patients and found 14/18 (78%) had seizures and ID however genetic analysis to see which of these had PTPS/PTS variants was not performed. PMID:9222757 report 1 case of seizures.
Genetic epilepsy syndromes v1.232 KCNA1 Rebecca Foulger Marked gene: KCNA1 as ready
Genetic epilepsy syndromes v1.232 KCNA1 Rebecca Foulger Gene: kcna1 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v1.232 KCNA1 Rebecca Foulger commented on gene: KCNA1: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is sufficient evidence to rate this gene Green. Kept rating as Green.
Undiagnosed metabolic disorders v1.152 HADH Sarah Leigh Deleted their comment
Genetic epilepsy syndromes v1.232 WDR62 Rebecca Foulger Marked gene: WDR62 as ready
Genetic epilepsy syndromes v1.232 WDR62 Rebecca Foulger Gene: wdr62 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v1.232 WDR62 Rebecca Foulger Classified gene: WDR62 as Amber List (moderate evidence)
Genetic epilepsy syndromes v1.232 WDR62 Rebecca Foulger Gene: wdr62 has been classified as Amber List (Moderate Evidence).
Undiagnosed metabolic disorders v1.152 HADH Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.152 HADH Sarah Leigh Deleted their comment
Genetic epilepsy syndromes v1.231 WDR62 Rebecca Foulger commented on gene: WDR62: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that this gene should be rated Amber- the microcephaly panels are more appropriate for testing. Demoted from Green to Amber.
Inborn errors of metabolism v1.143 GNMT Sarah Leigh Classified gene: GNMT as Green List (high evidence)
Inborn errors of metabolism v1.143 GNMT Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 3 variants reported in 2 unrelated cases, with supportive functional data.
Inborn errors of metabolism v1.143 GNMT Sarah Leigh Gene: gnmt has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v1.231 TSEN2 Rebecca Foulger Marked gene: TSEN2 as ready
Genetic epilepsy syndromes v1.231 TSEN2 Rebecca Foulger Gene: tsen2 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v1.231 TSEN2 Rebecca Foulger Classified gene: TSEN2 as Amber List (moderate evidence)
Genetic epilepsy syndromes v1.231 TSEN2 Rebecca Foulger Gene: tsen2 has been classified as Amber List (Moderate Evidence).
Inborn errors of metabolism v1.143 GNMT Sarah Leigh Phenotypes for gene: GNMT were changed from Glycine N-methyltransferase deficiency to Glycine N-methyltransferase deficiency 606664
Inborn errors of metabolism v1.142 GNMT Sarah Leigh Classified gene: GNMT as Green List (high evidence)
Inborn errors of metabolism v1.142 GNMT Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 3 variants reported in 2 unrelated cases, with supportive functional data.
Inborn errors of metabolism v1.142 GNMT Sarah Leigh Gene: gnmt has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v1.230 TSEN2 Rebecca Foulger commented on gene: TSEN2: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that this gene should be rated Amber because epilepsy is unlikely to be the primary presenting feature. Demoted from Green to Amber.
Inborn errors of metabolism v1.142 GNMT Sarah Leigh Classified gene: GNMT as Green List (high evidence)
Inborn errors of metabolism v1.142 GNMT Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 3 variants reported in 2 unrelated cases, with supportive functional data.
Inborn errors of metabolism v1.142 GNMT Sarah Leigh Gene: gnmt has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.152 GNMT Sarah Leigh Classified gene: GNMT as Green List (high evidence)
Undiagnosed metabolic disorders v1.152 GNMT Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 3 variants reported in 2 unrelated cases, with supportive functional data.
Undiagnosed metabolic disorders v1.152 GNMT Sarah Leigh Gene: gnmt has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v1.230 SCN9A Rebecca Foulger Marked gene: SCN9A as ready
Genetic epilepsy syndromes v1.230 SCN9A Rebecca Foulger Gene: scn9a has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v1.230 SCN9A Rebecca Foulger commented on gene: SCN9A: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is sufficient evidence to rate this gene Green. Kept rating as Green.
Genetic epilepsy syndromes v1.230 FLNA Rebecca Foulger Marked gene: FLNA as ready
Genetic epilepsy syndromes v1.230 FLNA Rebecca Foulger Gene: flna has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v1.230 FLNA Rebecca Foulger commented on gene: FLNA: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is sufficient evidence to rate this gene Green. Kept rating as Green.
Genetic epilepsy syndromes v1.230 FGFR3 Rebecca Foulger Classified gene: FGFR3 as Amber List (moderate evidence)
Genetic epilepsy syndromes v1.230 FGFR3 Rebecca Foulger Gene: fgfr3 has been classified as Amber List (Moderate Evidence).
Inborn errors of metabolism v1.141 GNMT Sarah Leigh Publications for gene: GNMT were set to 27604308; 17660255
Undiagnosed metabolic disorders v1.151 GNMT Sarah Leigh Publications for gene: GNMT were set to 27604308; 17660255
Genetic epilepsy syndromes v1.229 FGFR3 Rebecca Foulger Marked gene: FGFR3 as ready
Genetic epilepsy syndromes v1.229 FGFR3 Rebecca Foulger Gene: fgfr3 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v1.229 FGFR3 Rebecca Foulger Classified gene: FGFR3 as Amber List (moderate evidence)
Genetic epilepsy syndromes v1.229 FGFR3 Rebecca Foulger Gene: fgfr3 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v1.228 FGFR3 Rebecca Foulger commented on gene: FGFR3: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that this gene should be rated Amber because the Craniosynostosis panel is more appropriate for testing. Demoted from Green to Amber.
Genetic epilepsy syndromes v1.228 ATP1A2 Rebecca Foulger Marked gene: ATP1A2 as ready
Genetic epilepsy syndromes v1.228 ATP1A2 Rebecca Foulger Gene: atp1a2 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v1.228 ATP1A2 Rebecca Foulger commented on gene: ATP1A2: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is sufficient evidence to rate this gene Green. Kept rating as Green.
Inborn errors of metabolism v1.140 GLUL Sarah Leigh Classified gene: GLUL as Green List (high evidence)
Inborn errors of metabolism v1.140 GLUL Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 3 variants reported in unrelated cases.
Inborn errors of metabolism v1.140 GLUL Sarah Leigh Gene: glul has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.150 GLUL Sarah Leigh Classified gene: GLUL as Green List (high evidence)
Undiagnosed metabolic disorders v1.150 GLUL Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 3 variants reported in unrelated cases.
Undiagnosed metabolic disorders v1.150 GLUL Sarah Leigh Gene: glul has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.139 GLUL Sarah Leigh Publications for gene: GLUL were set to 27604308; 16267323; 21353613
Inborn errors of metabolism v1.139 GLUL Sarah Leigh Publications for gene: GLUL were set to 27604308
Undiagnosed metabolic disorders v1.149 GLUL Sarah Leigh Publications for gene: GLUL were set to 27604308
Undiagnosed metabolic disorders v1.148 GLUL Sarah Leigh Added comment: Comment on phenotypes: Glutamine deficiency, congenital (Other disorder of amino acid metabolism);Intellectual disability
Undiagnosed metabolic disorders v1.148 GLUL Sarah Leigh Phenotypes for gene: GLUL were changed from Glutamine deficiency, congenital (Other disorder of amino acid metabolism); Intellectual disability to Glutamine deficiency, congenital 610015
Inborn errors of metabolism v1.138 GLUL Sarah Leigh Added comment: Comment on phenotypes: Intellectual disability;Glutamine deficiency, congenital (Other disorder of amino acid metabolism)
Inborn errors of metabolism v1.138 GLUL Sarah Leigh Phenotypes for gene: GLUL were changed from Intellectual disability; Glutamine deficiency, congenital (Other disorder of amino acid metabolism) to Glutamine deficiency, congenital 610015
Undiagnosed metabolic disorders v1.147 GLUL Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.147 GK Sarah Leigh Classified gene: GK as Green List (high evidence)
Undiagnosed metabolic disorders v1.147 GK Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 8 variants reported.
Undiagnosed metabolic disorders v1.147 GK Sarah Leigh Gene: gk has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.146 GK Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.146 GK Sarah Leigh Deleted their comment
Inborn errors of metabolism v1.137 GK Sarah Leigh Mode of inheritance for gene: GK was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Membranoproliferative glomerulonephritis v1.15 CFB Eleanor Williams Classified gene: CFB as Green List (high evidence)
Membranoproliferative glomerulonephritis v1.15 CFB Eleanor Williams Added comment: Comment on list classification: Promoting from Amber to Green. Sufficient cases reported.
Membranoproliferative glomerulonephritis v1.15 CFB Eleanor Williams Gene: cfb has been classified as Green List (High Evidence).
Membranoproliferative glomerulonephritis v1.14 CFB Eleanor Williams changed review comment from: Associated with {Hemolytic uremic syndrome, atypical, susceptibility to, 4} (#612924) in OMIM.

PMID: 26283675 - Bu et al 2016 - screened 193 patients using a gene panel facilitate genetic testing in aHUS, TTP, C3GN, and DDD. Report 1 variant found in a patient with aHUS and 3 in patients with C3 glomerulonephritis. Individual patient and variant information not given.

PMID: 25758434 - Imamura et al 2015 - 1 family. Daughter diagnosed with C3 glomerulonephritis, mother treated for membranoproliferative glomerulonephritis, and brother with hypocomplementemia without urinary abnormalities. All 3 found to have heterozygosity for CFB p.S367R that was not present in the unaffected father or younger sister. Other variants were found in the daughter, CFI p.R201S and C3 p.V916I were excluded as in other unaffected individuals or appear in high frequency in other populations. They propose that it is highly likely that p.S367R causes a gain of function in CFB through a structure–function relationship.; to: Associated with {Hemolytic uremic syndrome, atypical, susceptibility to, 4} (#612924) in OMIM.

PMID: 28210841 - Alfakeeh et al 2017 - 7-year-old boy has pathological features compatible with IC-MPGN. A heterozygous variant p.Glu566Arg in exon 13 of the CFB gene was found.

PMID: 26283675 - Bu et al 2016 - screened 193 patients using a gene panel facilitate genetic testing in aHUS, TTP, C3GN, and DDD. Report 1 variant found in a patient with aHUS and 3 in patients with C3 glomerulonephritis. Individual patient and variant information not given.

PMID: 25758434 - Imamura et al 2015 - 1 family. Daughter diagnosed with C3 glomerulonephritis, mother treated for membranoproliferative glomerulonephritis, and brother with hypocomplementemia without urinary abnormalities. All 3 found to have heterozygosity for CFB p.S367R that was not present in the unaffected father or younger sister. Other variants were found in the daughter, CFI p.R201S and C3 p.V916I were excluded as in other unaffected individuals or appear in high frequency in other populations. They propose that it is highly likely that p.S367R causes a gain of function in CFB through a structure–function relationship.
Genetic epilepsy syndromes v1.228 LYST Rebecca Foulger Marked gene: LYST as ready
Genetic epilepsy syndromes v1.228 LYST Rebecca Foulger Gene: lyst has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v1.228 SETD5 Rebecca Foulger Marked gene: SETD5 as ready
Genetic epilepsy syndromes v1.228 SETD5 Rebecca Foulger Gene: setd5 has been classified as Amber List (Moderate Evidence).
Membranoproliferative glomerulonephritis v1.14 CFB Eleanor Williams Phenotypes for gene: CFB were changed from Haemolytic uraemic syndrome; aHUS; Hemolytic uremic syndrome, atypical, susceptibility to, 4, 612924; C3 glomerulopathy; C3G; Immune complex MPGN; IC-MPGN to Haemolytic uraemic syndrome; aHUS; Hemolytic uremic syndrome, atypical, susceptibility to, 4, 612924; C3 glomerulopathy; C3G; Immune complex MPGN; IC-MPGN; MPGN; Membranoproliferative glomerulonephritis
Genetic epilepsy syndromes v1.228 WDR45B Rebecca Foulger Marked gene: WDR45B as ready
Genetic epilepsy syndromes v1.228 WDR45B Rebecca Foulger Gene: wdr45b has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v1.228 WDR45B Rebecca Foulger Classified gene: WDR45B as Amber List (moderate evidence)
Genetic epilepsy syndromes v1.228 WDR45B Rebecca Foulger Gene: wdr45b has been classified as Amber List (Moderate Evidence).
Membranoproliferative glomerulonephritis v1.13 CFB Eleanor Williams Publications for gene: CFB were set to 25758434; 17182750; 21902819
Genetic epilepsy syndromes v1.227 WDR45B Rebecca Foulger commented on gene: WDR45B: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green, and an Amber rating is appropriate. Demoted from Green to Amber.
Genetic epilepsy syndromes v1.227 WDR45B Rebecca Foulger commented on gene: WDR45B: Re-reviewed this gene when curating panel for GMS Clinical Indication R59 Early onset or syndromic epilepsy. In summary, the evidence is borderline: PMID:28503735 (Suleiman et al) report 6 individuals from 3 families with homozygous pathogenic variants in WDR45B, and 2 of the families (5 indivs) had seizures- seizures were not reported in the sole individual from family 3.
Genetic epilepsy syndromes v1.227 SETD5 Rebecca Foulger Classified gene: SETD5 as Amber List (moderate evidence)
Genetic epilepsy syndromes v1.227 SETD5 Rebecca Foulger Gene: setd5 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v1.226 SETD5 Rebecca Foulger commented on gene: SETD5: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green, and an Amber rating is appropriate. Demoted from Green to Amber.
Genetic epilepsy syndromes v1.226 SETD5 Rebecca Foulger commented on gene: SETD5: Re-reviewed this gene when curating panel for GMS Clinical Indication R59 Early onset or syndromic epilepsy. Although four reviewers agreed it should be on EE panel, there is limited evidence of a seizure phenotype. PMID:26482601: (Kobayashi et al., 2016) examined 11 patients with early-onset epileptic encephalopathy, and SETD5 variants were amongst the findings. Therefore awaited clinical input on whether SETD5 should be demoted on this panel.
Membranoproliferative glomerulonephritis v1.12 CFB Eleanor Williams Added comment: Comment on mode of pathogenicity: Gain of function proposed
Membranoproliferative glomerulonephritis v1.12 CFB Eleanor Williams Mode of pathogenicity for gene: CFB was changed from to Other
Membranoproliferative glomerulonephritis v1.11 CFB Eleanor Williams Added comment: Comment on mode of inheritance: Familial case reported shows a monoallelic mode of inheritance
Membranoproliferative glomerulonephritis v1.11 CFB Eleanor Williams Mode of inheritance for gene: CFB was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Membranoproliferative glomerulonephritis v1.10 CFB Eleanor Williams commented on gene: CFB: Associated with {Hemolytic uremic syndrome, atypical, susceptibility to, 4} (#612924) in OMIM.

PMID: 26283675 - Bu et al 2016 - screened 193 patients using a gene panel facilitate genetic testing in aHUS, TTP, C3GN, and DDD. Report 1 variant found in a patient with aHUS and 3 in patients with C3 glomerulonephritis. Individual patient and variant information not given.

PMID: 25758434 - Imamura et al 2015 - 1 family. Daughter diagnosed with C3 glomerulonephritis, mother treated for membranoproliferative glomerulonephritis, and brother with hypocomplementemia without urinary abnormalities. All 3 found to have heterozygosity for CFB p.S367R that was not present in the unaffected father or younger sister. Other variants were found in the daughter, CFI p.R201S and C3 p.V916I were excluded as in other unaffected individuals or appear in high frequency in other populations. They propose that it is highly likely that p.S367R causes a gain of function in CFB through a structure–function relationship.
Genetic epilepsy syndromes v1.226 LYST Rebecca Foulger Classified gene: LYST as Amber List (moderate evidence)
Genetic epilepsy syndromes v1.226 LYST Rebecca Foulger Gene: lyst has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v1.225 LYST Rebecca Foulger commented on gene: LYST: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green, and an Amber rating is appropriate. Demoted from Green to Amber.
Genetic epilepsy syndromes v1.225 LYST Rebecca Foulger commented on gene: LYST: Re-reviewed this gene when curating panel for GMS Clinical Indication R59 Early onset or syndromic epilepsy. Although the mouse model displays seizures (PMID:16518687), there is limited evidence of patients with seizures (no mention of seizures in PMID:9215679, and one 1990 report of Chédiak-Higashi syndrome with seizures from PMID:10450360). Therefore awaiting clinical opinion on whether LYST should be demoted on this panel.
Genetic epilepsy syndromes v1.225 KIF1BP Rebecca Foulger Marked gene: KIF1BP as ready
Genetic epilepsy syndromes v1.225 KIF1BP Rebecca Foulger Gene: kif1bp has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v1.225 KIF1BP Rebecca Foulger Classified gene: KIF1BP as Amber List (moderate evidence)
Genetic epilepsy syndromes v1.225 KIF1BP Rebecca Foulger Gene: kif1bp has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v1.224 KIF1BP Rebecca Foulger commented on gene: KIF1BP: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green, and an Amber rating is appropriate. Demoted from Green to Amber.
Genetic epilepsy syndromes v1.224 KIF1BP Rebecca Foulger commented on gene: KIF1BP: Re-reviewed this gene when curating panel for GMS Clinical Indication R59 Early onset or syndromic epilepsy. Although the association with GOLDBERG-SHPRINTZEN MEGACOLON SYNDROME is strong, there is little direct evidence for seizures (PMID:28277559 identifies one case). Therefore awaiting clinical opinion on whether KIF1BP should be demoted.
Genetic epilepsy syndromes v1.224 GRIA2 Rebecca Foulger changed review comment from: PMID:8938126 (animal model): GluR2 heterozygous (+/−) mice showed reduced motor coordination but no sign of seizure activity as measured by observation, EEG, or post-mortem analysis.; to: PMID:8938126- animal model doesn't report seizures: GluR2 heterozygous (+/−) mice showed reduced motor coordination but no sign of seizure activity as measured by observation, EEG, or post-mortem analysis.
Genetic epilepsy syndromes v1.224 WDR37 Rebecca Foulger Classified gene: WDR37 as Green List (high evidence)
Genetic epilepsy syndromes v1.224 WDR37 Rebecca Foulger Gene: wdr37 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v1.223 WDR37 Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green.; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green. Promoted from Grey to Green.
Genetic epilepsy syndromes v1.223 WDR37 Rebecca Foulger commented on gene: WDR37: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green.
Genetic epilepsy syndromes v1.223 WDR37 Rebecca Foulger commented on gene: WDR37: WDR37 was added to the panel and rated Green by Konstantinos Varvagiannis. Although WDR37 is not yet associated with a disorder in OMIM or Gene2Phenotype, (as Konstantinos notes) there are sufficient unrelated cases from PMID:31327510 and PMID:31327508 with seizures (all 9 patients) for inclusion on the panel.
Genetic epilepsy syndromes v1.223 WDR37 Rebecca Foulger changed review comment from: Added missense tag: only missense variants reported so far (PMID:31327510).; to: Added missense tag: only missense variants reported so far (PMIDs 31327510, 31327508).
Genetic epilepsy syndromes v1.223 WDR37 Rebecca Foulger commented on gene: WDR37
Genetic epilepsy syndromes v1.223 WDR37 Rebecca Foulger Tag missense tag was added to gene: WDR37.
Genetic epilepsy syndromes v1.223 PIGU Rebecca Foulger Marked gene: PIGU as ready
Genetic epilepsy syndromes v1.223 PIGU Rebecca Foulger Gene: pigu has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v1.223 PIGH Rebecca Foulger Marked gene: PIGH as ready
Genetic epilepsy syndromes v1.223 PIGH Rebecca Foulger Gene: pigh has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v1.223 PIGC Rebecca Foulger Marked gene: PIGC as ready
Genetic epilepsy syndromes v1.223 PIGC Rebecca Foulger Gene: pigc has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v1.223 RRM2B Rebecca Foulger Marked gene: RRM2B as ready
Genetic epilepsy syndromes v1.223 RRM2B Rebecca Foulger Gene: rrm2b has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v1.223 TRAF7 Rebecca Foulger Marked gene: TRAF7 as ready
Genetic epilepsy syndromes v1.223 TRAF7 Rebecca Foulger Gene: traf7 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v1.223 TRAPPC12 Rebecca Foulger Marked gene: TRAPPC12 as ready
Genetic epilepsy syndromes v1.223 TRAPPC12 Rebecca Foulger Gene: trappc12 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v1.223 TRAPPC6B Rebecca Foulger Marked gene: TRAPPC6B as ready
Genetic epilepsy syndromes v1.223 TRAPPC6B Rebecca Foulger Gene: trappc6b has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v1.223 GNB5 Rebecca Foulger Marked gene: GNB5 as ready
Genetic epilepsy syndromes v1.223 GNB5 Rebecca Foulger Gene: gnb5 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v1.223 GNB5 Rebecca Foulger commented on gene: GNB5: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green.
Genetic epilepsy syndromes v1.223 TRAPPC6B Rebecca Foulger commented on gene: TRAPPC6B: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that this gene can remain as Amber.
Genetic epilepsy syndromes v1.223 TRAPPC12 Rebecca Foulger commented on gene: TRAPPC12: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that this gene can remain as Amber:
Genetic epilepsy syndromes v1.223 TRAF7 Rebecca Foulger commented on gene: TRAF7: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that this gene can remain as Amber: TRAF7 is Green on the Intellectual disability and Paediatric disorders panels, which would be appropriate for the presenting phenotype.
Genetic epilepsy syndromes v1.223 RRM2B Rebecca Foulger commented on gene: RRM2B: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that this gene can remain as Amber: RRM2B is Green on the 'Inborn errors of metabolism' panel (467) so will be Green on the Epilepsy Super panel (489).
Genetic epilepsy syndromes v1.223 PIGU Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that there is enough evidence to rate this gene Green: PIGx genes act in the same biochemical pathway. Promoted from Grey to Green.; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green: PIGx genes act in the same biochemical pathway. Promoted from Grey to Green.
Genetic epilepsy syndromes v1.223 PIGH Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that there is enough evidence to rate this gene Green: PIGx genes act in the same biochemical pathway. Promoted from Amber to Green.; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green: PIGx genes act in the same biochemical pathway. Promoted from Amber to Green.
Genetic epilepsy syndromes v1.223 PIGC Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that there is enough evidence to rate this gene Green: PIGx genes act in the same biochemical pathway. Promoted from Amber to Green.; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green: PIGx genes act in the same biochemical pathway. Promoted from Amber to Green.
Genetic epilepsy syndromes v1.223 PEX5 Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that this gene can remain as Amber: PEX5 is Green on the 'Inborn errors of metabolism' panel (467) so will be Green on the Epilepsy Super panel (489).; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that this gene can remain as Amber: PEX5 is Green on the 'Inborn errors of metabolism' panel (467) so will be Green on the Epilepsy Super panel (489).
Genetic epilepsy syndromes v1.223 KIAA1109 Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that there is enough evidence to rate this gene Green- although epilepsy may be secondary to the cerebral malformations presentation, include KIAA1109 so that cases recruited through different routes are not missed. Promoted from Amber to Green.; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green- although epilepsy may be secondary to the cerebral malformations presentation, include KIAA1109 so that cases recruited through different routes are not missed. Promoted from Amber to Green.
Genetic epilepsy syndromes v1.223 EIF2B3 Rebecca Foulger Classified gene: EIF2B3 as Green List (high evidence)
Genetic epilepsy syndromes v1.223 EIF2B3 Rebecca Foulger Gene: eif2b3 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v1.222 EIF2B3 Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that there is enough evidence to rate this gene Green. Epilepsy is a feature of Vanishing White Matter Disorder, and therefore should include on the panel for early diagnosis in children. Promoted from Amber to Green.; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green. Epilepsy is a feature of Vanishing White Matter Disorder, and therefore should include on the panel for early diagnosis in children. Promoted from Amber to Green.
Genetic epilepsy syndromes v1.222 EIF2B1 Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that there is enough evidence to rate this gene Green. Epilepsy is a feature of Vanishing White Matter Disorder, and therefore should include on the panel for early diagnosis in children. Promoted from Amber to Green.; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green. Epilepsy is a feature of Vanishing White Matter Disorder, and therefore should include on the panel for early diagnosis in children. Promoted from Amber to Green.
Genetic epilepsy syndromes v1.222 EFHC1 Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that this gene should remain as Amber: EFHC1 may be a susceptibility locus. Currently insufficient evidence to support a monogenic association with epilepsy.; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that this gene should remain as Amber: EFHC1 may be a susceptibility locus. Currently insufficient evidence to support a monogenic association with epilepsy.
Genetic epilepsy syndromes v1.222 DPM2 Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that this gene can remain as Amber: DPM2 is Green on the 'Inborn errors of metabolism' panel (467) so will be Green on the Epilepsy Super panel (489).; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that this gene can remain as Amber: DPM2 is Green on the 'Inborn errors of metabolism' panel (467) so will be Green on the Epilepsy Super panel (489).
Genetic epilepsy syndromes v1.222 CUL4B Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that there is enough evidence to rate this gene Green. Promoted from Amber to Green.; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green. Promoted from Amber to Green.
Genetic epilepsy syndromes v1.222 CNPY3 Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that there is enough evidence to rate this gene Green. Helen Lord (Oxford Medical Genetics Laboratories) notes that there are two further 2019 paper supporting inclusion. Promoted from Amber to Green.; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green. Helen Lord (Oxford Medical Genetics Laboratories) notes that there are two further 2019 paper supporting inclusion. Promoted from Amber to Green.
Intellectual disability v2.999 PIGU Rebecca Foulger Classified gene: PIGU as Green List (high evidence)
Intellectual disability v2.999 PIGU Rebecca Foulger Gene: pigu has been classified as Green List (High Evidence).
Intellectual disability v2.998 PIGU Rebecca Foulger commented on gene: PIGU: PIGU (together with other PIGx genes) were discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 to discuss R59 Early onset or syndromic epilepsy. Agreed that there is enough evidence to rate PIGU Green on the 'Genetic epilepsy syndromes' panel (402). Therefore applied Green rating to the ID panel also: although PIGU is not yet associated with a disorder in OMIM or Gene2Phenotype, there are sufficient unrelated cases described in PMID:31353022.
Intellectual disability v2.998 PIGU Rebecca Foulger commented on gene: PIGU: Added 'missense' tag as missense variants only reported so far (PMID:31353022).
Intellectual disability v2.998 PIGU Rebecca Foulger Tag missense tag was added to gene: PIGU.
Intellectual disability v2.998 PIGU Rebecca Foulger commented on gene: PIGU: PMID:31353022 (Knaus et al. 2019) report two homozygous missense mutations (c.209T>A [p.Ile70Lys] and c.1149C>A [p.Asn383Lys]) in 5 individuals from 3 unrelated families. All individuals presented with global DD severe-to-profound ID, muscular hypotonia, seizures, brain anomalies, scoliosis, and mild facial dysmorphism. Sequencing confirmed that all parents were healthy carriers. c.209T>A has not been observed in gnomAD while c.1149C>A has been observed only in the heterozygous state (7/277194).
Intellectual disability v2.998 PIGU Rebecca Foulger commented on gene: PIGU
Genetic epilepsy syndromes v1.222 PIGU Rebecca Foulger Phenotypes for gene: PIGU were changed from Global developmental delay; Intellectual disability; Seizures; Cerebral atrophy; Cerebellar hypoplasia; Scoliosis to myoclonic seizures; focal myoclonic seizures; Global developmental delay; Intellectual disability; Seizures; Cerebral atrophy; Cerebellar hypoplasia; Scoliosis
Genetic epilepsy syndromes v1.221 PIGU Rebecca Foulger Classified gene: PIGU as Green List (high evidence)
Genetic epilepsy syndromes v1.221 PIGU Rebecca Foulger Gene: pigu has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v1.220 PIGU Rebecca Foulger commented on gene: PIGU: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that there is enough evidence to rate this gene Green: PIGx genes act in the same biochemical pathway. Promoted from Grey to Green.
Genetic epilepsy syndromes v1.220 PIGU Rebecca Foulger changed review comment from: PMID:31353022 (Knaus et al. 2019) report two homozygous missense mutations (c.209T>A [p.Ile70Lys] and c.1149C>A [p.Asn383Lys]) in 5 individuals from 3 unrelated families. All individuals presented with global DD severe-to-profound ID, muscular hypotonia, seizures (myoclonic and focal myoclonic in all 5 probands), brain anomalies, scoliosis, and mild facial dysmorphism. Sequencing confirmed that all parents were healthy carriers. c.209T>A has not been observed in gnomAD while c.1149C>A has been observed only in the heterozygous state (7/277194).; to: PMID:31353022 (Knaus et al. 2019) report two homozygous missense mutations (c.209T>A [p.Ile70Lys] and c.1149C>A [p.Asn383Lys]) in 5 individuals from 3 unrelated families. All individuals presented with global DD severe-to-profound ID, muscular hypotonia, seizures (myoclonic/focal myoclonic in all 5 probands), brain anomalies, scoliosis, and mild facial dysmorphism. Sequencing confirmed that all parents were healthy carriers. c.209T>A has not been observed in gnomAD while c.1149C>A has been observed only in the heterozygous state (7/277194).
Genetic epilepsy syndromes v1.220 PIGU Rebecca Foulger commented on gene: PIGU: PIGU is not yet associated with a disorder in OMIM or Gene2Phenotype.
Genetic epilepsy syndromes v1.220 PIGU Rebecca Foulger commented on gene: PIGU: PMID:31353022 (Knaus et al. 2019) report two homozygous missense mutations (c.209T>A [p.Ile70Lys] and c.1149C>A [p.Asn383Lys]) in 5 individuals from 3 unrelated families. All individuals presented with global DD severe-to-profound ID, muscular hypotonia, seizures (myoclonic and focal myoclonic in all 5 probands), brain anomalies, scoliosis, and mild facial dysmorphism. Sequencing confirmed that all parents were healthy carriers. c.209T>A has not been observed in gnomAD while c.1149C>A has been observed only in the heterozygous state (7/277194).
Membranoproliferative glomerulonephritis v1.10 C3 Eleanor Williams Classified gene: C3 as Green List (high evidence)
Membranoproliferative glomerulonephritis v1.10 C3 Eleanor Williams Added comment: Comment on list classification: 2 cases plus functional data and expert review green.
Membranoproliferative glomerulonephritis v1.10 C3 Eleanor Williams Gene: c3 has been classified as Green List (High Evidence).
Membranoproliferative glomerulonephritis v1.9 C3 Eleanor Williams Publications for gene: C3 were set to 24172683; 20852386; 18796626; 21902819
Membranoproliferative glomerulonephritis v1.8 C3 Eleanor Williams Added comment: Comment on mode of pathogenicity: Gain of function
Membranoproliferative glomerulonephritis v1.8 C3 Eleanor Williams Mode of pathogenicity for gene: C3 was changed from to Other
Membranoproliferative glomerulonephritis v1.7 C3 Eleanor Williams Mode of inheritance for gene: C3 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Membranoproliferative glomerulonephritis v1.6 C3 Eleanor Williams commented on gene: C3: Associated with C3 deficiency (#613779) and {Hemolytic uremic syndrome, atypical, susceptibility to, 5} (#612925) in OMIM.

PMID: 20852386 - Martínez-Barricarte et al 2010 - report a case a mother and her two identical twin sons with Dense deposit disease (DDD) caused by a heterozygous variant in the C3 gene. The mutation, c.2767_2774delACGGTG (C3923ΔDG) in exon 21, results in a mutated protein (C3923ΔDG) lacking 2 amino acids (Asp923 and Gly924) in the MG7 domain of C3. The deletion was only present in affected family members. Functional studies suggest a gain of function.

PMID: 26471127 - Chauvet et al 2016 - report functional characterization of a C3 mutation identified in two brothers with C3GN (C3 glomerulopathy). Both carry the same c.2327T>C heterozygous mutation in the C3 gene, leading to p.I756T. The mutation was not found in the 1000 genomes or EVS databases. In vitro the C3 mutation exhibited decreased binding to CR1, resulting in less CR1-dependent cleavage of C3b by factor 1.
Atypical haemolytic uraemic syndrome v1.20 THBD Eleanor Williams Phenotypes for gene: THBD were changed from Hemolytic uremic syndrome, atypical, susceptibility to, 6, 612926 to Hemolytic uremic syndrome, atypical, susceptibility to, 6, 612926; Thrombophilia due to thrombomodulin defect 614486
Atypical haemolytic uraemic syndrome v1.19 VTN Eleanor Williams Phenotypes for gene: VTN were changed from to Atypical haemolytic uraemic syndrome; aHUS
Atypical haemolytic uraemic syndrome v1.18 VTN Eleanor Williams Publications for gene: VTN were set to
Atypical haemolytic uraemic syndrome v1.17 VTN Eleanor Williams Mode of inheritance for gene: VTN was changed from to Unknown
Atypical haemolytic uraemic syndrome v1.16 INF2 Eleanor Williams Phenotypes for gene: INF2 were changed from to Charcot-Marie-Tooth disease, dominant intermediate E, 614455; Glomerulosclerosis, focal segmental, 5, 613237
Atypical haemolytic uraemic syndrome v1.15 INF2 Eleanor Williams Publications for gene: INF2 were set to
Atypical haemolytic uraemic syndrome v1.14 INF2 Eleanor Williams Mode of inheritance for gene: INF2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Atypical haemolytic uraemic syndrome v1.13 MMACHC Eleanor Williams changed review comment from: PMID: 29068997 - Chen et al 2017 - 4-year-old girl with a diagnosis of aHUS. Genetic analysis revealed a compound heterozygous MMACHC mutation exonl: c. 80A >G, c. 609G >A. After treated by vitamin B12 for 10 days, the patient condition significantly improved. Note: her healthy younger sister also had both mutations. Her parents each had one of the variants.

PMID: 27324188 - Adrovic et al 2016 - describe the case of a 6-year-old girl with cblC disorder, who presented with severe multiorgan involvement at the age of 5 months and who was successfully treated with vitamin B12, betaine, coenzyme Q10 and l-carnitene, and who had a new homozygous mutation of MMACHC c. 484G > T, p.Gly162Trp

PMID: 24210589 - Cornec-Le Gall et al 2014 - Abstract only accessed. Describe a patient with atypical hemolytic uremic syndrome that did not respond to eculizumab. Very low plasma methionine levels associated with methylmalonic aciduria, which suggested cobalamin C disease. MMACHC sequencing revealed compound heterozygosity for 2 causative mutations.

PMID: 17874135 - Sharma et al 2007 - report a child diagnosed with Diarrhea-negative HUS secondary to cblC disease in infancy. Mutation analysis in this patient identified homozygosity for the 271 dupA mutation (c.271 dupA) in the cblC MMACHC gene.

PMID: 12210350 - Van Hove et al 2002 - Abstract only accessed. Report 2 siblings,with proteinuria and hematuria, hypertension, and chronic hemolytic anemia. Both patients had hyperhomocysteinemia and mild methylmalonic aciduria. Both patients and their father carry a balanced reciprocal translocation but the abstract does not state where in the genome this is.

PMID: 1593355 - Geraghty et al 1992 - Abstract only accessed. Describe a female infant with typical features of the cobalamin C form of combined methylmalonic aciduria and homocystinuria who also had the hemolytic-uremic syndrome with thrombocytopenia, microangiopathic hemolytic anemia, hypertension, and renal failure. No sequencing of the gene reported in the abstract.

PMID: 11972107 - Kind et al 2002 - a case of cobalamin C disease associated with hemolytic-uremic syndrome (HUS) in the neonatal period is described. No sequencing of the gene reported.; to: Associated with Methylmalonic aciduria and homocystinuria, cblC type (#277400) in OMIM.

PMID: 29068997 - Chen et al 2017 - 4-year-old girl with a diagnosis of aHUS. Genetic analysis revealed a compound heterozygous MMACHC mutation exonl: c. 80A >G, c. 609G >A. After treated by vitamin B12 for 10 days, the patient condition significantly improved. Note: her healthy younger sister also had both mutations. Her parents each had one of the variants.

PMID: 27324188 - Adrovic et al 2016 - describe the case of a 6-year-old girl with cblC disorder, who presented with severe multiorgan involvement at the age of 5 months and who was successfully treated with vitamin B12, betaine, coenzyme Q10 and l-carnitene, and who had a new homozygous mutation of MMACHC c. 484G > T, p.Gly162Trp

PMID: 24210589 - Cornec-Le Gall et al 2014 - Abstract only accessed. Describe a patient with atypical hemolytic uremic syndrome that did not respond to eculizumab. Very low plasma methionine levels associated with methylmalonic aciduria, which suggested cobalamin C disease. MMACHC sequencing revealed compound heterozygosity for 2 causative mutations.

PMID: 17874135 - Sharma et al 2007 - report a child diagnosed with Diarrhea-negative HUS secondary to cblC disease in infancy. Mutation analysis in this patient identified homozygosity for the 271 dupA mutation (c.271 dupA) in the cblC MMACHC gene.

PMID: 12210350 - Van Hove et al 2002 - Abstract only accessed. Report 2 siblings,with proteinuria and hematuria, hypertension, and chronic hemolytic anemia. Both patients had hyperhomocysteinemia and mild methylmalonic aciduria. Both patients and their father carry a balanced reciprocal translocation but the abstract does not state where in the genome this is.

PMID: 1593355 - Geraghty et al 1992 - Abstract only accessed. Describe a female infant with typical features of the cobalamin C form of combined methylmalonic aciduria and homocystinuria who also had the hemolytic-uremic syndrome with thrombocytopenia, microangiopathic hemolytic anemia, hypertension, and renal failure. No sequencing of the gene reported in the abstract.

PMID: 11972107 - Kind et al 2002 - a case of cobalamin C disease associated with hemolytic-uremic syndrome (HUS) in the neonatal period is described. No sequencing of the gene reported.
Atypical haemolytic uraemic syndrome v1.13 MMACHC Eleanor Williams Phenotypes for gene: MMACHC were changed from to Methylmalonic aciduria and homocystinuria, cblC type, 277400
Atypical haemolytic uraemic syndrome v1.12 MMACHC Eleanor Williams Publications for gene: MMACHC were set to
Atypical haemolytic uraemic syndrome v1.11 MMACHC Eleanor Williams Mode of inheritance for gene: MMACHC was changed from to BIALLELIC, autosomal or pseudoautosomal
Atypical haemolytic uraemic syndrome v1.10 MMACHC Eleanor Williams Classified gene: MMACHC as Green List (high evidence)
Atypical haemolytic uraemic syndrome v1.10 MMACHC Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green. More than 3 cases, with different variants reported, although in one case the healthy sister also had the same variants as the proband.
Atypical haemolytic uraemic syndrome v1.10 MMACHC Eleanor Williams Gene: mmachc has been classified as Green List (High Evidence).
Atypical haemolytic uraemic syndrome v1.9 MMACHC Eleanor Williams changed review comment from: PMID: 29068997 - Chen et al 2017 - 4-year-old girl with a diagnosis of aHUS. Genetic analysis revealed a compound heterozygous MMACHC mutation exonl: c. 80A >G, c. 609G >A. After treated by vitamin B12 for 10 days, the patient condition significantly improved. Note: her healthy younger sister also had both mutations. Her parents each had one of the variants.

PMID: 27324188 - Adrovic et al 2016 - describe the case of a 6-year-old girl with cblC disorder, who presented with severe multiorgan involvement at the age of 5 months and who was successfully treated with vitamin B12, betaine, coenzyme Q10 and l-carnitene, and who had a new homozygous mutation of MMACHC c. 484G > T, p.Gly162Trp

PMID: 24210589 - Cornec-Le Gall et al 2014 - Abstract only accessed. Describe a patient with atypical hemolytic uremic syndrome that did not respond to eculizumab. Very low plasma methionine levels associated with methylmalonic aciduria, which suggested cobalamin C disease. MMACHC sequencing revealed compound heterozygosity for 2 causative mutations.

PMID: 12210350 - Van Hove et al 2002 - Abstract only accessed. Report 2 siblings,with proteinuria and hematuria, hypertension, and chronic hemolytic anemia. Both patients had hyperhomocysteinemia and mild methylmalonic aciduria. Both patients and their father carry a balanced reciprocal translocation but the abstract does not state where in the genome this is.

PMID: 17874135 - Sharma et al 2007 - report a child diagnosed with Diarrhea-negative HUS secondary to cblC disease in infancy. Mutation analysis in this patient identified homozygosity for the 271 dupA mutation (c.271 dupA) in the cblC MMACHC gene.

PMID: 1593355 - Geraghty et al 1992 - Abstract only accessed. Describe a female infant with typical features of the cobalamin C form of combined methylmalonic aciduria and homocystinuria who also had the hemolytic-uremic syndrome with thrombocytopenia, microangiopathic hemolytic anemia, hypertension, and renal failure. No sequencing of the gene reported in the abstract.

PMID: 11972107 - Kind et al 2002 - a case of cobalamin C disease associated with hemolytic-uremic syndrome (HUS) in the neonatal period is described. No sequencing of the gene reported.; to: PMID: 29068997 - Chen et al 2017 - 4-year-old girl with a diagnosis of aHUS. Genetic analysis revealed a compound heterozygous MMACHC mutation exonl: c. 80A >G, c. 609G >A. After treated by vitamin B12 for 10 days, the patient condition significantly improved. Note: her healthy younger sister also had both mutations. Her parents each had one of the variants.

PMID: 27324188 - Adrovic et al 2016 - describe the case of a 6-year-old girl with cblC disorder, who presented with severe multiorgan involvement at the age of 5 months and who was successfully treated with vitamin B12, betaine, coenzyme Q10 and l-carnitene, and who had a new homozygous mutation of MMACHC c. 484G > T, p.Gly162Trp

PMID: 24210589 - Cornec-Le Gall et al 2014 - Abstract only accessed. Describe a patient with atypical hemolytic uremic syndrome that did not respond to eculizumab. Very low plasma methionine levels associated with methylmalonic aciduria, which suggested cobalamin C disease. MMACHC sequencing revealed compound heterozygosity for 2 causative mutations.

PMID: 17874135 - Sharma et al 2007 - report a child diagnosed with Diarrhea-negative HUS secondary to cblC disease in infancy. Mutation analysis in this patient identified homozygosity for the 271 dupA mutation (c.271 dupA) in the cblC MMACHC gene.

PMID: 12210350 - Van Hove et al 2002 - Abstract only accessed. Report 2 siblings,with proteinuria and hematuria, hypertension, and chronic hemolytic anemia. Both patients had hyperhomocysteinemia and mild methylmalonic aciduria. Both patients and their father carry a balanced reciprocal translocation but the abstract does not state where in the genome this is.

PMID: 1593355 - Geraghty et al 1992 - Abstract only accessed. Describe a female infant with typical features of the cobalamin C form of combined methylmalonic aciduria and homocystinuria who also had the hemolytic-uremic syndrome with thrombocytopenia, microangiopathic hemolytic anemia, hypertension, and renal failure. No sequencing of the gene reported in the abstract.

PMID: 11972107 - Kind et al 2002 - a case of cobalamin C disease associated with hemolytic-uremic syndrome (HUS) in the neonatal period is described. No sequencing of the gene reported.
Atypical haemolytic uraemic syndrome v1.9 MMACHC Eleanor Williams commented on gene: MMACHC: PMID: 29068997 - Chen et al 2017 - 4-year-old girl with a diagnosis of aHUS. Genetic analysis revealed a compound heterozygous MMACHC mutation exonl: c. 80A >G, c. 609G >A. After treated by vitamin B12 for 10 days, the patient condition significantly improved. Note: her healthy younger sister also had both mutations. Her parents each had one of the variants.

PMID: 27324188 - Adrovic et al 2016 - describe the case of a 6-year-old girl with cblC disorder, who presented with severe multiorgan involvement at the age of 5 months and who was successfully treated with vitamin B12, betaine, coenzyme Q10 and l-carnitene, and who had a new homozygous mutation of MMACHC c. 484G > T, p.Gly162Trp

PMID: 24210589 - Cornec-Le Gall et al 2014 - Abstract only accessed. Describe a patient with atypical hemolytic uremic syndrome that did not respond to eculizumab. Very low plasma methionine levels associated with methylmalonic aciduria, which suggested cobalamin C disease. MMACHC sequencing revealed compound heterozygosity for 2 causative mutations.

PMID: 12210350 - Van Hove et al 2002 - Abstract only accessed. Report 2 siblings,with proteinuria and hematuria, hypertension, and chronic hemolytic anemia. Both patients had hyperhomocysteinemia and mild methylmalonic aciduria. Both patients and their father carry a balanced reciprocal translocation but the abstract does not state where in the genome this is.

PMID: 17874135 - Sharma et al 2007 - report a child diagnosed with Diarrhea-negative HUS secondary to cblC disease in infancy. Mutation analysis in this patient identified homozygosity for the 271 dupA mutation (c.271 dupA) in the cblC MMACHC gene.

PMID: 1593355 - Geraghty et al 1992 - Abstract only accessed. Describe a female infant with typical features of the cobalamin C form of combined methylmalonic aciduria and homocystinuria who also had the hemolytic-uremic syndrome with thrombocytopenia, microangiopathic hemolytic anemia, hypertension, and renal failure. No sequencing of the gene reported in the abstract.

PMID: 11972107 - Kind et al 2002 - a case of cobalamin C disease associated with hemolytic-uremic syndrome (HUS) in the neonatal period is described. No sequencing of the gene reported.
Proteinuric renal disease v1.221 LAMA5 Eleanor Williams changed review comment from: Not associated with a phenotype in OMIM or Gene2Phenotype.

PMID: 29534211 - Braun et al 2019 - performed WES in 335 individuals of 300 families with Nephrotic syndrome and identified recessive mutations in the gene LAMA5 in three unrelated consanguineous families with childhood-onset NS that responded to immunosuppressive therapy. The 3 families were from Turkey, Egypt and Saudia Arabia and the following 3 missense variants were found - family A4389: c.2239 C >T, p.Arg747Trp, family B150: c.3002 A>G, p.Glu1001Gly, family B1284: c.8842 G>A, p.Gly2948Ser. In two families, the parents were shown to be heterozygous for the variants. None of the three variants has been reported in the homozygous state in databases of healthy control populations (EVS and gnomAD) although individuals of Middle Eastern descent are poorly represented in these databases. The authors state that because experimental evidence is lacking, the impact of these genetic variants on protein function and disease pathogenesis cannot be judged with certainty.; to: Not associated with a phenotype in OMIM or Gene2Phenotype.

PMID: 29534211 - Braun et al 2019 - performed WES in 335 individuals of 300 families with Nephrotic syndrome and identified recessive mutations in the gene LAMA5 in three unrelated consanguineous families with childhood-onset NS that responded to immunosuppressive therapy. The 3 families were from Turkey, Egypt and Saudia Arabia and the following 3 missense variants were found - family A4389: c.2239 C >T, p.Arg747Trp, family B150: c.3002 A>G, p.Glu1001Gly, family B1284: c.8842 G>A, p.Gly2948Ser. There is evolutionary conservation at these sites. In two families, the parents were shown to be heterozygous for the variants. None of the three variants has been reported in the homozygous state in databases of healthy control populations (EVS and gnomAD) although individuals of Middle Eastern descent are poorly represented in these databases. The authors state that because experimental evidence is lacking, the impact of these genetic variants on protein function and disease pathogenesis cannot be judged with certainty.
Proteinuric renal disease v1.221 LAMA5 Eleanor Williams changed review comment from: Not associated with a phenotype in OMIM or Gene2Phenotype.

PMID: 29534211 - Braun et al 2019 - performed WES in 335 individuals of 300 families with Nephrotic syndrome and identified recessive mutations in the gene LAMA5 in three unrelated consanguineous families with childhood-onset NS that responded to immunosuppressive therapy. The 3 families were from Turkey, Egypt and Saudia Arabia and the following 3 missense variants were found - family A4389: c.2239 C >T, p.Arg747Trp, family B150: c.3002 A>G, p.Glu1001Gly, family B1284: c.8842 G>A, p.Gly2948Ser. In two families, the parents were shown to be heterozygous for the variants. None of the three variants has been reported in the homozygous state in databases of healthy control populations (EVS and gnomAD) although individuals of Middle Eastern descent are poorly represented in these databases. The authors state that because experimental evidence is lacking, the impact of these genetic variants on protein function and disease pathogenesis cannot be judged with certainty.; to: Not associated with a phenotype in OMIM or Gene2Phenotype.

PMID: 29534211 - Braun et al 2019 - performed WES in 335 individuals of 300 families with Nephrotic syndrome and identified recessive mutations in the gene LAMA5 in three unrelated consanguineous families with childhood-onset NS that responded to immunosuppressive therapy. The 3 families were from Turkey, Egypt and Saudia Arabia and the following 3 missense variants were found - family A4389: c.2239 C >T, p.Arg747Trp, family B150: c.3002 A>G, p.Glu1001Gly, family B1284: c.8842 G>A, p.Gly2948Ser. In two families, the parents were shown to be heterozygous for the variants. None of the three variants has been reported in the homozygous state in databases of healthy control populations (EVS and gnomAD) although individuals of Middle Eastern descent are poorly represented in these databases. The authors state that because experimental evidence is lacking, the impact of these genetic variants on protein function and disease pathogenesis cannot be judged with certainty.
Proteinuric renal disease v1.221 LAMA5 Eleanor Williams commented on gene: LAMA5: Not associated with a phenotype in OMIM or Gene2Phenotype.

PMID: 29534211 - Braun et al 2019 - performed WES in 335 individuals of 300 families with Nephrotic syndrome and identified recessive mutations in the gene LAMA5 in three unrelated consanguineous families with childhood-onset NS that responded to immunosuppressive therapy. The 3 families were from Turkey, Egypt and Saudia Arabia and the following 3 missense variants were found - family A4389: c.2239 C >T, p.Arg747Trp, family B150: c.3002 A>G, p.Glu1001Gly, family B1284: c.8842 G>A, p.Gly2948Ser. In two families, the parents were shown to be heterozygous for the variants. None of the three variants has been reported in the homozygous state in databases of healthy control populations (EVS and gnomAD) although individuals of Middle Eastern descent are poorly represented in these databases. The authors state that because experimental evidence is lacking, the impact of these genetic variants on protein function and disease pathogenesis cannot be judged with certainty.
Amyloidosis v0.7 TTR Eleanor Williams commented on gene: TTR: Associated with Amyloidosis, hereditary, transthyretin-related (#105210) in OMIM. Lots of cases reported in OMIM.
Amelogenesis imperfecta v1.16 Eleanor Williams List of related panels changed from Amelogenesis Imperfecta to Amelogenesis Imperfecta; R340
Osteogenesis imperfecta v1.52 Eleanor Williams List of related panels changed from Osteogenesis Imperfecta to Osteogenesis Imperfecta; R102
Ehlers Danlos syndromes v1.63 ACTA2 Eleanor Williams Mode of inheritance for gene: ACTA2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Ehlers Danlos syndromes v1.62 MYLK Eleanor Williams commented on gene: MYLK: This gene is associated with Familial thoracic aortic aneurysm. Although patients with variants in this gene may present with EDS features it was decided following discussion in the GMS musculoskeletal specialist test group Webex on 2019-06-04 it to keep this gene amber. If more evidence of an overlap in phenotypes becomes available the rating can be reviewed.
Ehlers Danlos syndromes v1.62 Eleanor Williams List of related panels changed from 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 to 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
Craniosynostosis v1.127 TMCO1 Eleanor Williams Phenotypes for gene: TMCO1 were changed from MR syndrome; Cerebrofaciothoracic dysplasia/ craniofacial dysmorphism; skeletal anomalies to MR syndrome; Cerebrofaciothoracic dysplasia/ craniofacial dysmorphism; skeletal anomalies; Craniofacial dysmorphism, skeletal anomalies, and mental retardation syndrome, 213980
Craniosynostosis v1.126 TMCO1 Eleanor Williams changed review comment from: Associated with Craniofacial dysmorphism, skeletal anomalies, and mental retardation syndrome (#213980) in OMIM and Gene2Phenotype (confirmed)

PMID: 20018682 - Xin et al 2010 - identified an autosomal recessive condition in 11 individuals in the Old Order Amish of northeastern Ohio. The syndrome was characterized by distinctive craniofacial dysmorphism, skeletal anomalies, and mental retardation. They identified a homozygous frameshift mutation, c.139_140delAG, in TMCO1 in all affected members of the extended pedigree. 2 of the 11 individuals showed craniosynostosis.

PMID: 24424126 - Pehlivan et al 2014 - report a patient with cerebro-facio-thoracic dysplasia with a homozygous splice-site mutation TMC01 identified using WES. Cranial MRI revealed frontotemporal atrophy, dilated lateral ventricles and a short, dysgenetic corpus callosum.

PMID: 24194475 - Alanay et al 2013 - identified a homozygous nonsense founder mutation, p.Arg87Ter (c.259 C>T), in TMCO1 in 4 families of Turkish origin with Cerebrofaciothoracic dysplasia. Patient 4 from family 2 had a Prominent metopic suture (craniosynostosis).

3 cases with craniosynostosis reported.; to: Associated with Craniofacial dysmorphism, skeletal anomalies, and mental retardation syndrome (#213980) in OMIM and Gene2Phenotype (confirmed)

PMID: 20018682 - Xin et al 2010 - identified an autosomal recessive condition in 11 individuals in the Old Order Amish of northeastern Ohio. The syndrome was characterized by distinctive craniofacial dysmorphism, skeletal anomalies, and mental retardation. They identified a homozygous frameshift mutation, c.139_140delAG, in TMCO1 in all affected members of the extended pedigree. 2 of the 11 individuals showed craniosynostosis.

PMID: 24424126 - Pehlivan et al 2014 - report a patient with cerebro-facio-thoracic dysplasia with a homozygous splice-site mutation TMC01 identified using WES. Cranial MRI revealed frontotemporal atrophy, dilated lateral ventricles and a short, dysgenetic corpus callosum.

PMID: 24194475 - Alanay et al 2013 - identified a homozygous nonsense founder mutation, p.Arg87Ter (c.259 C>T), in TMCO1 in 4 families of Turkish origin with Cerebrofaciothoracic dysplasia. Patient 4 from family 2 had a Prominent metopic suture (craniosynostosis).

3 cases with craniosynostosis reported.

Other cases have been reported, but without craniosysnosotis e.g. PMID: 23320496, PMID: 31102500, PMID: 30556256
Craniosynostosis v1.126 TMCO1 Eleanor Williams Publications for gene: TMCO1 were set to
Craniosynostosis v1.125 TMCO1 Eleanor Williams Classified gene: TMCO1 as Green List (high evidence)
Craniosynostosis v1.125 TMCO1 Eleanor Williams Added comment: Comment on list classification: Promoting from red to green as there are 3 cases reported with craniosynostosis as a feature.
Craniosynostosis v1.125 TMCO1 Eleanor Williams Gene: tmco1 has been classified as Green List (High Evidence).
Craniosynostosis v1.124 TMCO1 Eleanor Williams commented on gene: TMCO1: Associated with Craniofacial dysmorphism, skeletal anomalies, and mental retardation syndrome (#213980) in OMIM and Gene2Phenotype (confirmed)

PMID: 20018682 - Xin et al 2010 - identified an autosomal recessive condition in 11 individuals in the Old Order Amish of northeastern Ohio. The syndrome was characterized by distinctive craniofacial dysmorphism, skeletal anomalies, and mental retardation. They identified a homozygous frameshift mutation, c.139_140delAG, in TMCO1 in all affected members of the extended pedigree. 2 of the 11 individuals showed craniosynostosis.

PMID: 24424126 - Pehlivan et al 2014 - report a patient with cerebro-facio-thoracic dysplasia with a homozygous splice-site mutation TMC01 identified using WES. Cranial MRI revealed frontotemporal atrophy, dilated lateral ventricles and a short, dysgenetic corpus callosum.

PMID: 24194475 - Alanay et al 2013 - identified a homozygous nonsense founder mutation, p.Arg87Ter (c.259 C>T), in TMCO1 in 4 families of Turkish origin with Cerebrofaciothoracic dysplasia. Patient 4 from family 2 had a Prominent metopic suture (craniosynostosis).

3 cases with craniosynostosis reported.
Craniosynostosis v1.124 SEC24D Eleanor Williams commented on gene: SEC24D: After review with clinical experts from the GMS musculoskeletal specialist test group it was decided to keep this gene as amber based on the level of evidence for craniosynostosis.
Craniosynostosis v1.124 KMT2D Eleanor Williams commented on gene: KMT2D: Associated with Kabuki syndrome (#147920) in OMIM with many cases reported.
Craniosynostosis v1.124 RUNX2 Eleanor Williams changed review comment from: Information about evidence for a CNV associated with Craniosynostosis has been submitted to ClinGen for curation (July 2019); to: Information about evidence for a CNV encompassing RUNX2 associated with Craniosynostosis has been submitted to ClinGen for curation (July 2019)
Craniosynostosis v1.124 RUNX2 Eleanor Williams commented on gene: RUNX2: Information about evidence for a CNV associated with Craniosynostosis has been submitted to ClinGen for curation (July 2019)
Craniosynostosis v1.124 Eleanor Williams List of related panels changed from Craniosynostosis syndromes; Craniosynostosis syndromes phenotypes; Rare syndromic craniosynostosis or isolated multisuture synostosis to Craniosynostosis syndromes; Craniosynostosis syndromes phenotypes; Rare syndromic craniosynostosis or isolated multisuture synostosis; R100
Severe early-onset obesity v1.17 TUB Ivone Leong Phenotypes for gene: TUB were changed from Retinal dystrophy and obesity (Borman (2014) Hum Mutat 35,289); ?Retinal dystrophy and obesity, 616188 to ?Retinal dystrophy and obesity, 616188
Common craniosynostosis syndromes v0.14 Eleanor Williams List of related panels changed from to R99
Severe early-onset obesity v1.16 TUB Ivone Leong Phenotypes for gene: TUB were changed from Retinal dystrophy and obesity (Borman (2014) Hum Mutat 35,289) to Retinal dystrophy and obesity (Borman (2014) Hum Mutat 35,289); ?Retinal dystrophy and obesity, 616188
Hearing loss v1.124 Eleanor Williams List of related panels changed from Congenital hearing impairment; Autosomal dominant deafness; Congenital hearing impairment (profound/severe) to Congenital hearing impairment; Autosomal dominant deafness; Congenital hearing impairment (profound/severe); R67
Hearing loss v1.123 GJB2 Eleanor Williams Publications for gene: GJB2 were set to PMID:10218527; 10369869; 10376574; 10422812; 10544226; 10607953; 10633133; 10633135; 10713883; 10757647; 10782932; 10807696; 10830906; 10874298; 10903123; 10980526; 10981905; 10982180; 10982182; 11134236; 11179004; 11298683; 11313751; 11313763; 11354642; 11483639; 11556849; 11746015; 11807148; 11912510; 11935342; 11977173; 12072059; 12080392; 12081719; 12107817; 12111646; 12121355; 12121617; 12172392; 12172394; 12176036; 12189487; 12189493; 12239718; 12372058; 12384501; 12384781; 12457154; 12484567; 12522556; 12548749; 12560944; 12668604; 12684873; 12700168; 12752120; 12786758; 12786762; 12833397; 12865758; 12920081; 1324944; 1370487; 14070830; 14505035; 14694360; 14700667; 14735592; 14985372; 14986832; 15150777; 15151513; 15235031; 15241677; 15253766; 15365987; 15482471; 15592461; 15633193; 15666300; 15700112; 15952212; 15996214; 16059934; 16088916; 16222667; 16380907; 16628254; 16650079; 16773579; 16840571; 16868655; 17036313; 17041943; 17256794; 17330861; 17426645; 17505205; 17660464; 17713529; 17935238; 17993581; 1849321; 18843290; 18925674; 18941476; 18985073; 19050930; 19340074; 19375528; 1964417; 20236118; 20412116; 20442751; 20815033; 21776002; 22031297; 22981120; 25262649; 2706105; 2956987; 8789457; 8978770; 9139825; 9285800; 9326398; 9328482; 9336442; 9358053; 9422505; 9471561; 9482292; 9482297; 9529365; 9620796; 9716127; 9819448; 9856479
Hearing loss v1.122 DIAPH1 Eleanor Williams changed review comment from: Comment on list classification: Upgrading from red to green after discussion with the GMS musculoskeletal specialist test group in a Webex on 2019-05-13 and consultation with the Genomics England clinical team; to: Comment on list classification: Upgrading from red to green after discussion with the GMS hearing loss specialist test group in a Webex and consultation with the Genomics England clinical team
Amyloidosis v0.7 LYZ Eleanor Williams commented on gene: LYZ: Associated with Amyloidosis, renal (#105200) in OMIM.

PMID: 21988333 - Sattianayagam et al 2012 - 16 Caucasian patients from 8 families with all with Lysozyme amyloidosis, except for asymptomatic patient. 12 patients were heterozygous for a mutation in the lysozyme gene that encodes the D67H variant, 2 cases carried the W64R variant and 1 case each carried the I56T and D67G variants.
Genetic epilepsy syndromes v1.220 PIGH Rebecca Foulger Classified gene: PIGH as Green List (high evidence)
Genetic epilepsy syndromes v1.220 PIGH Rebecca Foulger Gene: pigh has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v1.219 PIGH Rebecca Foulger commented on gene: PIGH: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that there is enough evidence to rate this gene Green: PIGx genes act in the same biochemical pathway. Promoted from Amber to Green.
Genetic epilepsy syndromes v1.219 PIGC Rebecca Foulger Classified gene: PIGC as Green List (high evidence)
Genetic epilepsy syndromes v1.219 PIGC Rebecca Foulger Gene: pigc has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v1.218 PIGC Rebecca Foulger commented on gene: PIGC: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that there is enough evidence to rate this gene Green: PIGx genes act in the same biochemical pathway. Promoted from Amber to Green.
Genetic epilepsy syndromes v1.218 PEX5 Rebecca Foulger commented on gene: PEX5: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that this gene can remain as Amber: PEX5 is Green on the 'Inborn errors of metabolism' panel (467) so will be Green on the Epilepsy Super panel (489).
Genetic epilepsy syndromes v1.218 KIAA1109 Rebecca Foulger Classified gene: KIAA1109 as Green List (high evidence)
Genetic epilepsy syndromes v1.218 KIAA1109 Rebecca Foulger Gene: kiaa1109 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v1.217 KIAA1109 Rebecca Foulger commented on gene: KIAA1109: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that there is enough evidence to rate this gene Green- although epilepsy may be secondary to the cerebral malformations presentation, include KIAA1109 so that cases recruited through different routes are not missed. Promoted from Amber to Green.
Inborn errors of metabolism v1.136 GK Sarah Leigh Publications for gene: GK were set to 27604308
Undiagnosed metabolic disorders v1.146 GK Sarah Leigh Publications for gene: GK were set to 27604308
Genetic epilepsy syndromes v1.217 GTPBP3 Rebecca Foulger commented on gene: GTPBP3: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that this gene can remain as Amber: GTPBP3 is Green on the 'Inborn errors of metabolism' panel (467) so will be Green on the Epilepsy Super panel (489).
Genetic epilepsy syndromes v1.217 EIF2B3 Rebecca Foulger Classified gene: EIF2B3 as Amber List (moderate evidence)
Genetic epilepsy syndromes v1.217 EIF2B3 Rebecca Foulger Gene: eif2b3 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v1.216 EIF2B3 Rebecca Foulger commented on gene: EIF2B3: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that there is enough evidence to rate this gene Green. Epilepsy is a feature of Vanishing White Matter Disorder, and therefore should include on the panel for early diagnosis in children. Promoted from Amber to Green.
Amyloidosis v0.7 GSN Eleanor Williams commented on gene: GSN: Associated with Amyloidosis, Finnish type (#105120) in OMIM

PMID: 25342098 - Rowczenio et al - report the clinical features in 10 patients with hereditary gelsolin (AGel) amyloidosis associated with the p.D214N mutation. Two patients, from the same kindred presented with proteinuria; eight subjects had a characteristic AGel amyloidosis phenotype including cranial neuropathy and/or corneal lattice dystrophy.

PMID: 24601799 - Efebera et al 2014 - report a novel gelsolin variant in a 62-year-old man with nephrotic range proteinuria. DNA sequencing revealed the novel gelsolin mutation (c.633C > A) encoding p.N211K protein variant. 4 of 13 asymptomatic family members were found to be heterozygous for the p.N211K mutation, three of whom had proteinuria of varying degree including one who proceeded to renal biopsy and was confirmed to have renal amyloidosis.

PMID: 22938848 - Sethi et al 2013 - report a 75-year-old woman who presented with progressive kidney failure. Kidney biopsy showed amyloidosis of undetermined type. Sequencing of the gelsolin gene revealed a previously undescribed sequence variant, a guanine to adenine substitution at nucleotide 580 of the coding sequence, corresponding to a predicted glycine to arginine mutation at amino acid 194.
Genetic epilepsy syndromes v1.216 EIF2B1 Rebecca Foulger Classified gene: EIF2B1 as Green List (high evidence)
Genetic epilepsy syndromes v1.216 EIF2B1 Rebecca Foulger Gene: eif2b1 has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.135 GK Sarah Leigh Classified gene: GK as Green List (high evidence)
Inborn errors of metabolism v1.135 GK Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 8 variants reported.
Inborn errors of metabolism v1.135 GK Sarah Leigh Gene: gk has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.145 GK Sarah Leigh Classified gene: GK as Green List (high evidence)
Undiagnosed metabolic disorders v1.145 GK Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 8 variants reported.
Undiagnosed metabolic disorders v1.145 GK Sarah Leigh Gene: gk has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v1.215 EIF2B1 Rebecca Foulger commented on gene: EIF2B1: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that there is enough evidence to rate this gene Green. Epilepsy is a feature of Vanishing White Matter Disorder, and therefore should include on the panel for early diagnosis in children. Promoted from Amber to Green.
Genetic epilepsy syndromes v1.215 EFHC1 Rebecca Foulger commented on gene: EFHC1: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that this gene should remain as Amber: EFHC1 may be a susceptibility locus. Currently insufficient evidence to support a monogenic association with epilepsy.
Undiagnosed metabolic disorders v1.144 GK Sarah Leigh Added comment: Comment on mode of inheritance: This moi has been changed to be in with OMIM and Gen2Phen.
Undiagnosed metabolic disorders v1.144 GK Sarah Leigh Mode of inheritance for gene: GK was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Inborn errors of metabolism v1.134 GK Sarah Leigh Deleted their comment
Inborn errors of metabolism v1.134 GK Sarah Leigh Added comment: Comment on mode of inheritance: This moi has been changed to be in with OMIM and Gen2Phen.
Inborn errors of metabolism v1.134 GK Sarah Leigh Mode of inheritance for gene: GK was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Genetic epilepsy syndromes v1.215 DPM2 Rebecca Foulger commented on gene: DPM2: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that this gene can remain as Amber: DPM2 is Green on the 'Inborn errors of metabolism' panel (467) so will be Green on the Epilepsy Super panel (489).
Inborn errors of metabolism v1.134 GK Sarah Leigh Added comment: Comment on mode of inheritance: This moi has been changed to be in with OMIM and Gen2Phen.
Inborn errors of metabolism v1.134 GK Sarah Leigh Mode of inheritance for gene: GK was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Inborn errors of metabolism v1.133 GK Sarah Leigh Mode of inheritance for gene: GK 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
Undiagnosed metabolic disorders v1.143 GK Sarah Leigh Mode of inheritance for gene: GK 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
Undiagnosed metabolic disorders v1.142 GK Sarah Leigh Added comment: Comment on phenotypes: Glycerol kinase deficiency (Disorders of glycerol metabolism);Intellectual disability;Intellectual_disability
Undiagnosed metabolic disorders v1.142 GK Sarah Leigh Phenotypes for gene: GK were changed from Glycerol kinase deficiency (Disorders of glycerol metabolism); Intellectual disability; Intellectual_disability to Glycerol kinase deficiency 307030
Inborn errors of metabolism v1.132 GK Sarah Leigh Added comment: Comment on phenotypes: Glycerol kinase deficiency (Disorders of glycerol metabolism);Intellectual disability;Intellectual_disability
Inborn errors of metabolism v1.132 GK Sarah Leigh Phenotypes for gene: GK were changed from Glycerol kinase deficiency (Disorders of glycerol metabolism); Intellectual disability; Intellectual_disability to Glycerol kinase deficiency 307030
Undiagnosed metabolic disorders v1.141 GK Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.141 GK Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.141 GK Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.141 GAMT Sarah Leigh Publications for gene: GAMT were set to 27604308
Undiagnosed metabolic disorders v1.140 GAMT Sarah Leigh Classified gene: GAMT as Green List (high evidence)
Undiagnosed metabolic disorders v1.140 GAMT Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 5 variants reported in 4 unrelated cases.
Undiagnosed metabolic disorders v1.140 GAMT Sarah Leigh Gene: gamt has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.131 GAMT Sarah Leigh Classified gene: GAMT as Green List (high evidence)
Inborn errors of metabolism v1.131 GAMT Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 5 variants reported in 4 unrelated cases.
Inborn errors of metabolism v1.131 GAMT Sarah Leigh Gene: gamt has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v1.215 CUL4B Rebecca Foulger Classified gene: CUL4B as Green List (high evidence)
Genetic epilepsy syndromes v1.215 CUL4B Rebecca Foulger Gene: cul4b has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v1.214 CUL4B Rebecca Foulger commented on gene: CUL4B: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that there is enough evidence to rate this gene Green. Promoted from Amber to Green.
Genetic epilepsy syndromes v1.214 CNPY3 Rebecca Foulger Classified gene: CNPY3 as Green List (high evidence)
Genetic epilepsy syndromes v1.214 CNPY3 Rebecca Foulger Gene: cnpy3 has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.130 GAMT Sarah Leigh Publications for gene: GAMT were set to 27604308
Genetic epilepsy syndromes v1.213 CNPY3 Rebecca Foulger commented on gene: CNPY3: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that there is enough evidence to rate this gene Green. Helen Lord (Oxford Medical Genetics Laboratories) notes that there are two further 2019 paper supporting inclusion. Promoted from Amber to Green.
Inborn errors of metabolism v1.129 GAMT Sarah Leigh Added comment: Comment on phenotypes: Intellectual disability;Guanidinoacetate methyltransferase deficiency (Mitochondrial respiratory chain disorders (caused by nuclear variants only), disorders of creatinine metabolism)
Inborn errors of metabolism v1.129 GAMT Sarah Leigh Phenotypes for gene: GAMT were changed from Intellectual disability; Guanidinoacetate methyltransferase deficiency (Mitochondrial respiratory chain disorders (caused by nuclear variants only), disorders of creatinine metabolism) to Cerebral creatine deficiency syndrome 2 612736
Amyloidosis v0.7 FGA Eleanor Williams commented on gene: FGA: Associated with Amyloidosis, familial visceral (#105200) in OMIM.

PMID: 29142973 - Rowczenio et al 2016 - 6 patients presented with proteinuria, hypertension, and/or lower limb edema. A novel FGA gene mutation was identified in each case: 2 frameshift mutations F521Sfs*27 and G519Efs*30 and 4 single base substitutions G555F, E526K, E524K, R554H. In 5 patients amyloid deposits were found only within the glomeruli. In 1 patient light-chain amyloid deposits were found.

PMID: 23551149 - Haidinger et al 2013 - large Spanish family with chronic kidney disease with late-onset gross proteinuria. Renal biopsies from 2 members revealed almost complete obliteration of the mesangial glomerular architecture, although kidney function was only moderately impaired. In these 2 living members, they identified the AFib R554L mutation.

PMID: 19073821 - Gillmore et al 2009 - describe 71 patients with fibrinogen amyloidosis, who were prospectively studied at the UK National Amyloidosis Centre. Direct sequencing of the FGA gene showed that 64 patients were heterozygous for the previously reported single base substitution that altered the codon at position 526 of the mature protein from that for glutamic acid to valine. 2 English patients were heterozygous for the previously reported fibrinogen mutation encoding a single base substitution that altered the codon at position 554 from arginine to leucine. 4 novel amyloidogenic fibrinogen mutations were discovered in Chinese, German and Afro-Caribbean patients.
Genetic epilepsy syndromes v1.213 NPRL2 Rebecca Foulger commented on gene: NPRL2: NPRL2 re-reviewed for curation of GMS epilepsy panel: Sufficient cases for inclusion but variants in unaffected family members (explained by the authors as incomplete penetrance). Other members of the complex, NPRL3 and DEPDC5, are Green on the panel. Since the last curation there has been a Green review by Deb Pal (Kings College London): PMID:30093711 (2019) note 3 further probands with epilepsy (including 1 with infantile spasm and unclear effect on the protein). They also note incomplete penetrance for variants in their cohort of 73 patients (covering DEPDC5 + NPRL2 + NPRL3 genes which all form the GATOR1 complex together). Awaiting clinical review for final gene rating.
Undiagnosed metabolic disorders v1.139 FTCD Sarah Leigh Publications for gene: FTCD were set to 27604308
Undiagnosed metabolic disorders v1.138 FTCD Sarah Leigh Classified gene: FTCD as Green List (high evidence)
Undiagnosed metabolic disorders v1.138 FTCD Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 15 variants reported.
Undiagnosed metabolic disorders v1.138 FTCD Sarah Leigh Gene: ftcd has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.128 FTCD Sarah Leigh Classified gene: FTCD as Green List (high evidence)
Inborn errors of metabolism v1.128 FTCD Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 15 variants reported.
Inborn errors of metabolism v1.128 FTCD Sarah Leigh Gene: ftcd has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.127 FTCD Sarah Leigh Publications for gene: FTCD were set to 27604308; 12815595
Inborn errors of metabolism v1.126 FTCD Sarah Leigh Publications for gene: FTCD were set to 27604308
Inborn errors of metabolism v1.125 FTCD Sarah Leigh Phenotypes for gene: FTCD were changed from Glutamate formiminotransferase deficiency to Glutamate formiminotransferase deficiency 229100
Undiagnosed metabolic disorders v1.137 FGFR2 Sarah Leigh Mode of inheritance for gene: FGFR2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Inborn errors of metabolism v1.124 FGFR2 Sarah Leigh Classified gene: FGFR2 as Green List (high evidence)
Inborn errors of metabolism v1.124 FGFR2 Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with 14 phenotypes in OMIM and as confirmed Gen2Phen gene for acrocephalosyndactyly type V, Antley-Bixler syndrome, Apert syndrome, Beare-Stevenson cutis gyrata syndrome, Crouzon syndrome, familial scaphocephaly syndrome, Jackson-Weiss syndrome, lacrimo-auriculo-dento-digital syndrome. At least 44 variants reported.
Inborn errors of metabolism v1.124 FGFR2 Sarah Leigh Gene: fgfr2 has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.136 FGFR2 Sarah Leigh Classified gene: FGFR2 as Green List (high evidence)
Undiagnosed metabolic disorders v1.136 FGFR2 Sarah Leigh Added comment: Comment on list classification: Associated with 14 phenotypes in OMIM and as confirmed Gen2Phen gene for acrocephalosyndactyly type V, Antley-Bixler syndrome, Apert syndrome, Beare-Stevenson cutis gyrata syndrome, Crouzon syndrome, familial scaphocephaly syndrome, Jackson-Weiss syndrome, lacrimo-auriculo-dento-digital syndrome. At least 44 variants reported.
Undiagnosed metabolic disorders v1.136 FGFR2 Sarah Leigh Gene: fgfr2 has been classified as Green List (High Evidence).
Amyloidosis v0.7 CST3 Eleanor Williams commented on gene: CST3: Associated with Cerebral amyloid angiopathy (#105150) in PubMed

PMID: 2900981 - Palsdottir et al 1988 - abstract only accessed - 8 families with Hereditary cystatin C amyloid angiopathy and a mutation in the codon for leucine at position 68. The mutation affects a Alu I restriction site and from this it has been found that the mutation is transmitted only in affected members of the families.

PMID: 3495457 - Abrahamson et al 1987 - 1 case - report that the deposited fragment from a patient with hereditary cerebral hemorrhage with amyloidosis had a L68Q substitution.

PMID: 1352269 - Abrahamson et al 1992 - 4 HCCAA patients of four different families were analyzed by nucleotide sequencing; the HCCAA-causing mutation in all families was found to be a single T----A substitution in the codon for amino acid residue 68 of cystatin C.

PMID: 3673496 - Jensson et al 1987 - abstract only accessed - but OMIM report that they found abnormal cystatin C protein sequences in the amyloid protein deposited in patients with Icelandic-type amyloidosis. Abnormalities included absence of 10 amino acids from the amino terminal and an amino acid substitution at position 58, which corresponded to position 68 in cystatin C.

PMID: 7482672 - Graffagnino et al 1995 - report a case of sporadic Cerebral amyloid angiopathy (CAA) with intracerebral hemorrhage (ICH) in an elderly Croatian man with a mutation in cystatin C identical to that found in Icelandic hereditary cerebral hemorrhage with amyloidosis.

Same substitution L68Q in all cases reported so far, with it appearing to be a founder mutation in the Icelandic cases, with only one sporadic cases from a non-Icelandic individual.
Undiagnosed metabolic disorders v1.135 FGFR2 Sarah Leigh Phenotypes for gene: FGFR2 were changed from Antley-Bixler syndrome type without disordered steroidogenesis; Arthrogryposis; Bilateral microtia; Choanal atresia; Craniosynostosis syndromes phenotypes; Deafness and congenital structural abnormalities; Unexplained skeletal dysplasia to Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis 207410; Apert syndrome 101200; Beare-Stevenson cutis gyrata syndrome 123790; Bent bone dysplasia syndrome 614592; Craniofacial-skeletal-dermatologic dysplasia 101600; Craniosynostosis, nonspecific; Crouzon syndrome 123500; Gastric cancer, somatic 613659; Jackson-Weiss syndrome 123150; LADD syndrome 149730; Pfeiffer syndrome 101600; Saethre-Chotzen syndrome 101400; Scaphocephaly and Axenfeld-Rieger anomaly; Scaphocephaly, maxillary retrusion, and mental retardation 609579
Undiagnosed metabolic disorders v1.134 FGFR2 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.134 FGFR2 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.134 FGFR2 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.134 FGFR2 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.134 FGFR2 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.134 FGFR2 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.134 FGFR2 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.134 FGFR2 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.134 FGFR2 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.134 FGFR2 Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.134 FGFR2 Sarah Leigh Deleted their comment
Inborn errors of metabolism v1.123 FGFR2 Sarah Leigh Phenotypes for gene: FGFR2 were changed from Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis 207410; Apert syndrome 101200; Beare-Stevenson cutis gyrata syndrome 123790; Bent bone dysplasia syndrome 614592; Craniofacial-skeletal-dermatologic dysplasia 101600; Craniosynostosis, nonspecific; Crouzon syndrome 123500; Gastric cancer, somatic 613659; Jackson-Weiss syndrome 123150; LADD syndrome 149730; Pfeiffer syndrome 101600; Saethre-Chotzen syndrome 101400; Scaphocephaly and Axenfeld-Rieger anomaly; Scaphocephaly, maxillary retrusion, and mental retardation 609579 to Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis 207410; Apert syndrome 101200; Beare-Stevenson cutis gyrata syndrome 123790; Bent bone dysplasia syndrome 614592; Craniofacial-skeletal-dermatologic dysplasia 101600; Craniosynostosis, nonspecific; Crouzon syndrome 123500; Gastric cancer, somatic 613659; Jackson-Weiss syndrome 123150; LADD syndrome 149730; Pfeiffer syndrome 101600; Saethre-Chotzen syndrome 101400; Scaphocephaly and Axenfeld-Rieger anomaly; Scaphocephaly, maxillary retrusion, and mental retardation 609579
Inborn errors of metabolism v1.122 FGFR2 Sarah Leigh Phenotypes for gene: FGFR2 were changed from Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis 207410; Apert syndrome 101200; Beare-Stevenson cutis gyrata syndrome 123790; Bent bone dysplasia syndrome 614592; Craniofacial-skeletal-dermatologic dysplasia 101600; Craniosynostosis, nonspecific; Crouzon syndrome 123500; Gastric cancer, somatic 613659; Jackson-Weiss syndrome 123150; LADD syndrome 149730; Pfeiffer syndrome 101600; Saethre-Chotzen syndrome 101400; Scaphocephaly and Axenfeld-Rieger anomaly; Scaphocephaly, maxillary retrusion, and mental retardation 609579 to Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis 207410; Apert syndrome 101200; Beare-Stevenson cutis gyrata syndrome 123790; Bent bone dysplasia syndrome 614592; Craniofacial-skeletal-dermatologic dysplasia 101600; Craniosynostosis, nonspecific; Crouzon syndrome 123500; Gastric cancer, somatic 613659; Jackson-Weiss syndrome 123150; LADD syndrome 149730; Pfeiffer syndrome 101600; Saethre-Chotzen syndrome 101400; Scaphocephaly and Axenfeld-Rieger anomaly; Scaphocephaly, maxillary retrusion, and mental retardation 609579
Inborn errors of metabolism v1.122 FGFR2 Sarah Leigh Phenotypes for gene: FGFR2 were changed from Bilateral microtia; Deafness and congenital structural abnormalities; Craniosynostosis syndromes phenotypes; Arthrogryposis; Choanal atresia; Antley-Bixler syndrome type without disordered steroidogenesis; Unexplained skeletal dysplasia to Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis 207410; Apert syndrome 101200; Beare-Stevenson cutis gyrata syndrome 123790; Bent bone dysplasia syndrome 614592; Craniofacial-skeletal-dermatologic dysplasia 101600; Craniosynostosis, nonspecific; Crouzon syndrome 123500; Gastric cancer, somatic 613659; Jackson-Weiss syndrome 123150; LADD syndrome 149730; Pfeiffer syndrome 101600; Saethre-Chotzen syndrome 101400; Scaphocephaly and Axenfeld-Rieger anomaly; Scaphocephaly, maxillary retrusion, and mental retardation 609579
Inborn errors of metabolism v1.121 FGFR2 Sarah Leigh Mode of inheritance for gene: FGFR2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic epilepsy syndromes v1.213 IKBKG Rebecca Foulger Added comment: Comment on mode of inheritance: OMIM lists XLD inheritance for Incontinentia pigmenti (MIM:308300).
Genetic epilepsy syndromes v1.213 IKBKG Rebecca Foulger Mode of inheritance for gene: IKBKG 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, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Inborn errors of metabolism v1.120 FECH Sarah Leigh Classified gene: FECH as Green List (high evidence)
Inborn errors of metabolism v1.120 FECH Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with phenotype in OMIM and not in Gen2Phen. At least 16 variants identified in unrelated cases.
Inborn errors of metabolism v1.120 FECH Sarah Leigh Gene: fech has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.119 FECH Sarah Leigh Phenotypes for gene: FECH were changed from Protoporphyria, erythropoietic, 1 177000 to Protoporphyria, erythropoietic, 1 177000
Inborn errors of metabolism v1.119 FECH Sarah Leigh Phenotypes for gene: FECH were changed from Erythropoietic protoporphyria, mild variant; Erythropoietic protoporphyria (Porphyrias with acute painful photosensitivity) to Protoporphyria, erythropoietic, 1 177000
Undiagnosed metabolic disorders v1.134 DPM3 Sarah Leigh Phenotypes for gene: DPM3 were changed from DMP3-CDG (other congenital disorders of glycosylation); Congenital disorder of glycosylation, type Io 612937 to Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 15 612937
Undiagnosed metabolic disorders v1.133 DPM3 Sarah Leigh Publications for gene: DPM3 were set to 27604308
Undiagnosed metabolic disorders v1.132 DPM3 Sarah Leigh Classified gene: DPM3 as Green List (high evidence)
Undiagnosed metabolic disorders v1.132 DPM3 Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 2 variants reported as homozygotes in two unrelated cases, together with segregation and supportive functional studies.
Undiagnosed metabolic disorders v1.132 DPM3 Sarah Leigh Gene: dpm3 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v1.212 ARHGEF9 Rebecca Foulger Added comment: Comment on mode of inheritance: OMIM lists XLR mode of inheritance for 'Epileptic encephalopathy, early infantile, 8' (MIM:300607). Gene2Phenotype lists hemizygous mode of inheritance (XLR) for EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 8.
Genetic epilepsy syndromes v1.212 ARHGEF9 Rebecca Foulger Mode of inheritance for gene: ARHGEF9 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Inborn errors of metabolism v1.118 DPM3 Sarah Leigh Classified gene: DPM3 as Green List (high evidence)
Inborn errors of metabolism v1.118 DPM3 Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 2 variants reported as homozygotes in two unrelated cases, together with segregation and supportive functional studies.
Inborn errors of metabolism v1.118 DPM3 Sarah Leigh Gene: dpm3 has been classified as Green List (High Evidence).
Congenital disorders of glycosylation v1.31 DPM3 Sarah Leigh Classified gene: DPM3 as Green List (high evidence)
Congenital disorders of glycosylation v1.31 DPM3 Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 2 variants reported as homozygotes in two unrelated cases, together with segregation and supportive functional studies.
Congenital disorders of glycosylation v1.31 DPM3 Sarah Leigh Gene: dpm3 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v1.211 NDUFA1 Rebecca Foulger Added comment: Comment on mode of inheritance: There is a case of female with variant and symptoms in PMID:21596602. (Mayr et al., 2011), but she does not have epilepsy but rather a metabolic defect. Therefore XLD is appropriate for metabolism panel but MOI is kept as XLR on this epilepsy panel for now.
Genetic epilepsy syndromes v1.211 NDUFA1 Rebecca Foulger Mode of inheritance for gene: NDUFA1 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Congenital disorders of glycosylation v1.30 DPM3 Sarah Leigh Phenotypes for gene: DPM3 were changed from Congenital disorder of glycosylation, type Io 612937 to Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 15 612937
Inborn errors of metabolism v1.117 DPM3 Sarah Leigh Publications for gene: DPM3 were set to 19576565; 28803818
Congenital disorders of glycosylation v1.29 DPM3 Sarah Leigh Publications for gene: DPM3 were set to 19576565
Inborn errors of metabolism v1.117 DPM3 Sarah Leigh Publications for gene: DPM3 were set to 19576565
Inborn errors of metabolism v1.116 DPM3 Sarah Leigh Phenotypes for gene: DPM3 were changed from Congenital disorder of glycosylation, type Io 612937; Congenital disorder of glycosylation, type Io 612937; DMP3-CDG (other congenital disorders of glycosylation) to Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 15 612937
Neurodegenerative disorders - adult onset v1.98 GBA Louise Daugherty changed review comment from: Comment on list classification: As discussed with the GMS Neurology Specialist Test Group webex call Friday 26th July 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Amber.; to: Comment on list classification: As discussed with the GMS Neurology Specialist Test Group webex call Friday 26th July 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Amber. Rating changed from Green to Amber
Inborn errors of metabolism v1.115 DHDDS Sarah Leigh Classified gene: DHDDS as Amber List (moderate evidence)
Inborn errors of metabolism v1.115 DHDDS Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM and as probable Gen2Phen gene for Retinitis pigmentosa 59 613861. One variant was reported in at least 15 families with retinitis pigmentosa, but only one compound individual with glycosylation defects was identifed so far (PMID 27343064).
Inborn errors of metabolism v1.115 DHDDS Sarah Leigh Gene: dhdds has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v1.210 SLC16A2 Rebecca Foulger Added comment: Comment on mode of inheritance: MOI is recorded as hemizygous in Gene2Phenotype and XL in OMIM. XLR inheritance was confirmed with reviewer, as stated by Ellen McDonagh.
Genetic epilepsy syndromes v1.210 SLC16A2 Rebecca Foulger Mode of inheritance for gene: SLC16A2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Amyloidosis v0.7 B2M Eleanor Williams changed review comment from: Provisionally associated with ?Amyloidosis, familial visceral (#105200) in OMIM.

PMID: 22693999 - Valleix et al 2012 - report a French family with 4 members who had progressive bowel dysfunction with extensive visceral amyloid deposits composed of β2-microglobulin. All the members of this family had normal circulating concentrations of β2-microglobulin and normal renal function. A heterozygous mutation in the B2M gene was found in each of the affected family members c.286G→A, Asp76Asn. The 3 unaffected family members tested were all wild type. The Asp76Asn β2-microglobulin variant was thermodynamically unstable and remarkably fibrillogenic in vitro under physiological conditions.; to: Provisionally associated with ?Amyloidosis, familial visceral (#105200) in OMIM.

PMID: 22693999 - Valleix et al 2012 - report a French family with 4 members who had progressive bowel dysfunction with extensive visceral amyloid deposits composed of β2-microglobulin. All the members of this family had normal circulating concentrations of β2-microglobulin and normal renal function. A heterozygous mutation in the B2M gene was found in each of the affected family members c.286G→A, Asp76Asn. The 3 unaffected family members tested were all wild type. The Asp76Asn β2-microglobulin variant was thermodynamically unstable and remarkably fibrillogenic in vitro under physiological conditions.

A PubMed search did not reveal any further cases.
Amyloidosis v0.7 APOC3 Eleanor Williams commented on gene: APOC3: Associated with Apolipoprotein C-III deficiency (#614028) only in OMIM.

PMID: 26790392 - Valleix et al 2016 - report a French family with severe renal amyloidosis and hypotriglyceridemia, both caused by a novel D25V apoC-III variant. The D25V apoC-III variant was only found in family members affected with amyloidosis, hypotriglyceridemia and reduced apoC-III levels, and not in healthy normotriglycemic family members.

A PubMed search with APOC3 or Apolipoprotein C-III and amyloidosis did not find any further cases.
Genetic epilepsy syndromes v1.209 PIGA Rebecca Foulger Added comment: Comment on mode of inheritance: OMIM records XLR inheritance for 'Multiple congenital anomalies-hypotonia-seizures syndrome 2 (MIM:300868). Gene2Phenotype reports 'hemizygous' allelic requirement for MULTIPLE CONGENITAL ANOMALIES-HYPOTONIA-SEIZURES SYNDROME 2. Johnston et al., 2012 (PMID:22305531) report 3 deceased males and 2 carrier females. Both carrier females had 100% skewed X-inactivation and neither presented with a phenotype.
Genetic epilepsy syndromes v1.209 PIGA Rebecca Foulger Mode of inheritance for gene: PIGA was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Inborn errors of metabolism v1.114 DHDDS Sarah Leigh Added comment: Comment on phenotypes: Posterior segment abnormalities;Retinitis pigmentosa (other congenital disorders of glycosylation)
Inborn errors of metabolism v1.114 DHDDS Sarah Leigh Phenotypes for gene: DHDDS were changed from ?Congenital disorder of glycosylation, type 1bb 613861; Developmental delay and seizures with or without movement abnormalities 617836; Retinitis pigmentosa 59 613861 to Retinitis pigmentosa 59 613861; ?Congenital disorder of glycosylation, type 1bb 613861
Genetic epilepsy syndromes v1.208 MED12 Rebecca Foulger Added comment: Comment on mode of inheritance: Allelic requirement listed in Gene2Phenotype is 'hemizygous' for both 'OPITZ-KAVEGGIA SYNDROME' and 'LUJAN-FRYNS SYNDROME'.
Genetic epilepsy syndromes v1.208 MED12 Rebecca Foulger Mode of inheritance for gene: MED12 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Congenital disorders of glycosylation v1.28 DHDDS Sarah Leigh Phenotypes for gene: DHDDS were changed from Retinitis pigmentosa 59 613861 to Retinitis pigmentosa 59 613861; ?Congenital disorder of glycosylation, type 1bb 613861
Neurodegenerative disorders - adult onset v1.98 GBA Louise Daugherty Classified gene: GBA as Amber List (moderate evidence)
Neurodegenerative disorders - adult onset v1.98 GBA Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Neurology Specialist Test Group webex call Friday 26th July 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Amber.
Neurodegenerative disorders - adult onset v1.98 GBA Louise Daugherty Gene: gba has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v1.207 MAGI2 Rebecca Foulger Added comment: Comment on mode of inheritance: OMIM lists AR inheritance for 'Nephrotic syndrome, type 15' (MIM:617609). Gene2Phenotype lists 'monoallelic' inheritance for EARLY ONSET EPILEPTIC ENCEPHALOPATHY.
Genetic epilepsy syndromes v1.207 MAGI2 Rebecca Foulger Mode of inheritance for gene: MAGI2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic epilepsy syndromes v1.206 IDH2 Rebecca Foulger Added comment: Comment on mode of inheritance: The mode of inheritance for IDH2 is currently MONOALLELIC on the 'Intellectual disability' panel, and the 'Inborn errors of metabolism' panel.
Genetic epilepsy syndromes v1.206 IDH2 Rebecca Foulger Mode of inheritance for gene: IDH2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Periodic fever syndromes v1.11 APOC2 Eleanor Williams commented on gene: APOC2
Genetic epilepsy syndromes v1.205 IDH2 Rebecca Foulger Phenotypes for gene: IDH2 were changed from D-2-hydroxyglutaric aciduria 2 to D-2-hydroxyglutaric aciduria 2, 613657
Genetic epilepsy syndromes v1.204 IDH2 Rebecca Foulger Publications for gene: IDH2 were set to
Genetic epilepsy syndromes v1.203 NRXN1 Rebecca Foulger Added comment: Comment on mode of inheritance: PMID:30031152 (Al Shehhi et al.) report heterozygous deletions of NRXN1 with phenotypes including seizures. At least PMID:21964664 (Harrison et al.) and PMID:19896112 report a biallelic mode of inheritance.
Genetic epilepsy syndromes v1.203 NRXN1 Rebecca Foulger Mode of inheritance for gene: NRXN1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Amyloidosis v0.7 APOC2 Eleanor Williams changed review comment from: Associated with Hyperlipoproteinemia, type Ib (#207750) in OMIM.

PMID: 30197986 - Sethi et al 2018 - report 5 older adults (mean 71.6 years at diagnosis) presented with nephrotic-range proteinuria. All renal biopsy specimens showed massive mesangial nodules composed of weakly eosinophilic, periodic acid-Schiff negative, Congo red-positive amyloid deposits. APOC2 p.Lys41Thr mutant protein was found by mass spectrometry in amyloid deposits of all patients. DNA sequencing in 1 patient confirmed the presence of the mutation.

PMID: 27297947 - Nasr et al 2017 - report an initial patient and then 7 others with kidney involvement and with Apo-CII-rich amyloid deposits. DNA sequencing of the APOC2 gene in the initial patient and one of her children detected a heterozygous c.206A→T transition, causing an E69V missense mutation. They also detected the mutant peptide in the proband's renal amyloid deposits.

Only 2 patients sequenced but in the Sethi et al paper the mutant protein was found in 4 more patients.; to: Associated with Hyperlipoproteinemia, type Ib (#207750) in OMIM.

PMID: 30197986 - Sethi et al 2018 - report 5 older adults (mean 71.6 years at diagnosis) presented with nephrotic-range proteinuria. All renal biopsy specimens showed massive mesangial nodules composed of weakly eosinophilic, periodic acid-Schiff negative, Congo red-positive amyloid deposits. APOC2 p.Lys41Thr mutant protein was found by mass spectrometry in amyloid deposits of all patients. DNA sequencing in 1 patient confirmed the presence of the mutation.

PMID: 27297947 - Nasr et al 2017 - report an initial patient and then 7 others with kidney involvement and with Apo-CII-rich amyloid deposits. DNA sequencing of the APOC2 gene in the initial patient and one of her children detected a heterozygous c.206A→T transition, causing an E69V missense mutation. They also detected the mutant peptide in the proband's renal amyloid deposits.

PMID: 27840752 - Lohani et al 2016 - 61-year-old female presenting with renal failure and nephrotic syndrome. No sequencing but laser microdissection and liquid chromatography mass spectrometry detected high levels of apolipoprotein C-II.

Only 2 patients sequenced but in the Sethi et al paper the mutant protein was found in 4 more patients.
Genetic epilepsy syndromes v1.202 SLC35A2 Rebecca Foulger Added comment: Comment on mode of inheritance: MOI in OMIM for SLC35A2 is listed as X-linked dominant.
Genetic epilepsy syndromes v1.202 SLC35A2 Rebecca Foulger Mode of inheritance for gene: SLC35A2 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, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Amyloidosis v0.7 APOC2 Eleanor Williams changed review comment from: Not associated with a relevant phenotype in OMIM

PMID: 30197986 - Sethi et al 2018 - report 5 older adults (mean 71.6 years at diagnosis) presented with nephrotic-range proteinuria. All renal biopsy specimens showed massive mesangial nodules composed of weakly eosinophilic, periodic acid-Schiff negative, Congo red-positive amyloid deposits. APOC2 p.Lys41Thr mutant protein was found by mass spectrometry in amyloid deposits of all patients. DNA sequencing in 1 patient confirmed the presence of the mutation.

PMID: 27297947 - Nasr et al 2017 - report an initial patient and then 7 others with kidney involvement and with Apo-CII-rich amyloid deposits. DNA sequencing of the APOC2 gene in the initial patient and one of her children detected a heterozygous c.206A→T transition, causing an E69V missense mutation. They also detected the mutant peptide in the proband's renal amyloid deposits.

Only 2 patients sequenced but in the Sethi et al paper the mutant protein was found in 4 more patients.; to: Associated with Hyperlipoproteinemia, type Ib (#207750) in OMIM.

PMID: 30197986 - Sethi et al 2018 - report 5 older adults (mean 71.6 years at diagnosis) presented with nephrotic-range proteinuria. All renal biopsy specimens showed massive mesangial nodules composed of weakly eosinophilic, periodic acid-Schiff negative, Congo red-positive amyloid deposits. APOC2 p.Lys41Thr mutant protein was found by mass spectrometry in amyloid deposits of all patients. DNA sequencing in 1 patient confirmed the presence of the mutation.

PMID: 27297947 - Nasr et al 2017 - report an initial patient and then 7 others with kidney involvement and with Apo-CII-rich amyloid deposits. DNA sequencing of the APOC2 gene in the initial patient and one of her children detected a heterozygous c.206A→T transition, causing an E69V missense mutation. They also detected the mutant peptide in the proband's renal amyloid deposits.

Only 2 patients sequenced but in the Sethi et al paper the mutant protein was found in 4 more patients.
Undiagnosed metabolic disorders v1.131 DHDDS Sarah Leigh Deleted their comment
Undiagnosed metabolic disorders v1.131 DHDDS Sarah Leigh changed review comment from: Amber review assigned as this gene is Green on the V1 panel(s) named as a phenotype(s); to: Amber review assigned as this gene is Green on the V1 panel(s) named as a phenotype(s)
Fetal anomalies v0.339 SLC35A2 Rebecca Foulger Mode of inheritance for gene: SLC35A2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Fetal anomalies v0.338 SLC35A2 Rebecca Foulger Added comment: Comment on mode of inheritance: Gene2Phenotype currently records a 'monoallelic' MOI for SLC35A2 for 'CONGENITAL DISORDER OF GLYCOSYLATION'. Changed MOI from 'monoallelic' to 'XLD' because SLC35A2 is on the X-chromosome.
Fetal anomalies v0.338 SLC35A2 Rebecca Foulger Mode of inheritance for gene: SLC35A2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Amyloidosis v0.7 APOC2 Eleanor Williams commented on gene: APOC2: Not associated with a relevant phenotype in OMIM

PMID: 30197986 - Sethi et al 2018 - report 5 older adults (mean 71.6 years at diagnosis) presented with nephrotic-range proteinuria. All renal biopsy specimens showed massive mesangial nodules composed of weakly eosinophilic, periodic acid-Schiff negative, Congo red-positive amyloid deposits. APOC2 p.Lys41Thr mutant protein was found by mass spectrometry in amyloid deposits of all patients. DNA sequencing in 1 patient confirmed the presence of the mutation.

PMID: 27297947 - Nasr et al 2017 - report an initial patient and then 7 others with kidney involvement and with Apo-CII-rich amyloid deposits. DNA sequencing of the APOC2 gene in the initial patient and one of her children detected a heterozygous c.206A→T transition, causing an E69V missense mutation. They also detected the mutant peptide in the proband's renal amyloid deposits.

Only 2 patients sequenced but in the Sethi et al paper the mutant protein was found in 4 more patients.
Adult onset movement disorder v0.101 WDR73 Louise Daugherty Source Expert Review Red was added to WDR73.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 VAC14 Louise Daugherty Source Expert Review Red was added to VAC14.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 TUBA1A Louise Daugherty Source Expert Review Red was added to TUBA1A.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 TH Louise Daugherty Source Expert Review Red was added to TH.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 SURF1 Louise Daugherty Source Expert Review Red was added to SURF1.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 SUCLG1 Louise Daugherty Source Expert Review Red was added to SUCLG1.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 SUCLA2 Louise Daugherty Source Expert Review Red was added to SUCLA2.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 SLC6A5 Louise Daugherty Source Expert Review Red was added to SLC6A5.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 SLC6A3 Louise Daugherty Source Expert Review Red was added to SLC6A3.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 SLC39A14 Louise Daugherty Source Expert Review Red was added to SLC39A14.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 SLC25A19 Louise Daugherty Source Expert Review Red was added to SLC25A19.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 SLC1A3 Louise Daugherty Source Expert Review Red was added to SLC1A3.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 SERAC1 Louise Daugherty Source Expert Review Red was added to SERAC1.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 SDHA Louise Daugherty Source Expert Review Red was added to SDHA.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 SCN8A Louise Daugherty Source Expert Review Red was added to SCN8A.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 SCN1A Louise Daugherty Source Expert Review Red was added to SCN1A.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 PDP1 Louise Daugherty Source Expert Review Red was added to PDP1.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 PDHA1 Louise Daugherty Source Expert Review Red was added to PDHA1.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 PCCB Louise Daugherty Source Expert Review Red was added to PCCB.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 PCCA Louise Daugherty Source Expert Review Red was added to PCCA.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 OPA3 Louise Daugherty Source Expert Review Red was added to OPA3.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 OCLN Louise Daugherty Source Expert Review Red was added to OCLN.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 NKX6-2 Louise Daugherty Source Expert Review Red was added to NKX6-2.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 NDUFV1 Louise Daugherty Source Expert Review Red was added to NDUFV1.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 NDUFS8 Louise Daugherty Source Expert Review Red was added to NDUFS8.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 NDUFS7 Louise Daugherty Source Expert Review Red was added to NDUFS7.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 NDUFS4 Louise Daugherty Source Expert Review Red was added to NDUFS4.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 NDUFAF6 Louise Daugherty Source Expert Review Red was added to NDUFAF6.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 NDUFAF2 Louise Daugherty Source Expert Review Red was added to NDUFAF2.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 NDUFA10 Louise Daugherty Source Expert Review Red was added to NDUFA10.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 NDUFA1 Louise Daugherty Source Expert Review Red was added to NDUFA1.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 MUT Louise Daugherty Source Expert Review Red was added to MUT.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 MECR Louise Daugherty Source Expert Review Red was added to MECR.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 KCNQ3 Louise Daugherty Source Expert Review Red was added to KCNQ3.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 KCNQ2 Louise Daugherty Source Expert Review Red was added to KCNQ2.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 KCNA1 Louise Daugherty Source Expert Review Red was added to KCNA1.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 IVD Louise Daugherty Source Expert Review Red was added to IVD.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 ISG15 Louise Daugherty Source Expert Review Red was added to ISG15.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 IFIH1 Louise Daugherty Source Expert Review Red was added to IFIH1.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 HTRA2 Louise Daugherty Source Expert Review Red was added to HTRA2.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 HIBCH Louise Daugherty Source Expert Review Red was added to HIBCH.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 GNAO1 Louise Daugherty Source Expert Review Red was added to GNAO1.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 GLRB Louise Daugherty Source Expert Review Red was added to GLRB.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 GLRA1 Louise Daugherty Source Expert Review Red was added to GLRA1.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 GCDH Louise Daugherty Source Expert Review Red was added to GCDH.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 FOXP2 Louise Daugherty Source Expert Review Red was added to FOXP2.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 FA2H Louise Daugherty Source Expert Review Red was added to FA2H.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 ETHE1 Louise Daugherty Source Expert Review Red was added to ETHE1.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 DLAT Louise Daugherty Source Expert Review Red was added to DLAT.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 CSTB Louise Daugherty Source Expert Review Red was added to CSTB.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 COX15 Louise Daugherty Source Expert Review Red was added to COX15.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 COX10 Louise Daugherty Source Expert Review Red was added to COX10.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 COASY Louise Daugherty Source Expert Review Red was added to COASY.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 CACNB4 Louise Daugherty Source Expert Review Red was added to CACNB4.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 BCS1L Louise Daugherty Source Expert Review Red was added to BCS1L.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 BCAP31 Louise Daugherty Source Expert Review Red was added to BCAP31.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 AP1S2 Louise Daugherty Source Expert Review Red was added to AP1S2.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 ADCY5 Louise Daugherty Source Expert Review Red was added to ADCY5.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset movement disorder v0.101 ADAR Louise Daugherty Source Expert Review Red was added to ADAR.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Glycogen storage disease v1.0 Sarah Leigh promoted panel to version 1.0
Adult onset movement disorder v0.100 WDR73 Louise Daugherty commented on gene: WDR73: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 VAC14 Louise Daugherty commented on gene: VAC14: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 TUBA1A Louise Daugherty commented on gene: TUBA1A: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 TH Louise Daugherty commented on gene: TH: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 SURF1 Louise Daugherty commented on gene: SURF1: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 SUCLG1 Louise Daugherty commented on gene: SUCLG1: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 SUCLA2 Louise Daugherty commented on gene: SUCLA2: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 SLC6A5 Louise Daugherty commented on gene: SLC6A5: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 SLC6A3 Louise Daugherty commented on gene: SLC6A3: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 SLC39A14 Louise Daugherty commented on gene: SLC39A14: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 SLC25A19 Louise Daugherty commented on gene: SLC25A19: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 SLC1A3 Louise Daugherty commented on gene: SLC1A3: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 SERAC1 Louise Daugherty commented on gene: SERAC1: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 SDHA Louise Daugherty commented on gene: SDHA: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 SCN8A Louise Daugherty commented on gene: SCN8A: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 SCN1A Louise Daugherty commented on gene: SCN1A: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 PDP1 Louise Daugherty commented on gene: PDP1: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 PDHA1 Louise Daugherty commented on gene: PDHA1: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 PCCB Louise Daugherty commented on gene: PCCB: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 PCCA Louise Daugherty commented on gene: PCCA: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 OPA3 Louise Daugherty commented on gene: OPA3: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 OCLN Louise Daugherty commented on gene: OCLN: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 NKX6-2 Louise Daugherty commented on gene: NKX6-2: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 NDUFV1 Louise Daugherty commented on gene: NDUFV1: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 NDUFS8 Louise Daugherty commented on gene: NDUFS8: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 NDUFS7 Louise Daugherty commented on gene: NDUFS7: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 NDUFS4 Louise Daugherty commented on gene: NDUFS4: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 NDUFAF6 Louise Daugherty commented on gene: NDUFAF6: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 NDUFAF2 Louise Daugherty commented on gene: NDUFAF2: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 NDUFA10 Louise Daugherty commented on gene: NDUFA10: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 NDUFA1 Louise Daugherty commented on gene: NDUFA1: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 MUT Louise Daugherty commented on gene: MUT: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 MECR Louise Daugherty commented on gene: MECR: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 KCNQ3 Louise Daugherty commented on gene: KCNQ3: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 KCNQ2 Louise Daugherty commented on gene: KCNQ2: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 KCNA1 Louise Daugherty commented on gene: KCNA1: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 IVD Louise Daugherty commented on gene: IVD: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 ISG15 Louise Daugherty commented on gene: ISG15: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 IFIH1 Louise Daugherty commented on gene: IFIH1: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 HTRA2 Louise Daugherty commented on gene: HTRA2: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 HIBCH Louise Daugherty commented on gene: HIBCH: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 GNAO1 Louise Daugherty commented on gene: GNAO1: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 GLRB Louise Daugherty commented on gene: GLRB: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 GLRA1 Louise Daugherty commented on gene: GLRA1: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 GCDH Louise Daugherty commented on gene: GCDH: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 FOXP2 Louise Daugherty commented on gene: FOXP2: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 FA2H Louise Daugherty commented on gene: FA2H: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 ETHE1 Louise Daugherty commented on gene: ETHE1: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 DLAT Louise Daugherty commented on gene: DLAT: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 CSTB Louise Daugherty commented on gene: CSTB: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 COX15 Louise Daugherty commented on gene: COX15: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 COX10 Louise Daugherty commented on gene: COX10: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 COASY Louise Daugherty commented on gene: COASY: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 CACNB4 Louise Daugherty commented on gene: CACNB4: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 BCS1L Louise Daugherty commented on gene: BCS1L: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 BCAP31 Louise Daugherty commented on gene: BCAP31: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 AP1S2 Louise Daugherty commented on gene: AP1S2: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 ADCY5 Louise Daugherty commented on gene: ADCY5: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Adult onset movement disorder v0.100 ADAR Louise Daugherty commented on gene: ADAR: Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.
Glycogen storage disease v0.5 Sarah Leigh List of related panels changed from to R274
Panel types changed to GMS Rare Disease; GMS signed-off
Adult onset movement disorder v0.99 YY1 Louise Daugherty commented on gene: YY1: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 WDR73 Louise Daugherty commented on gene: WDR73: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 VAC14 Louise Daugherty commented on gene: VAC14: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 TUBA1A Louise Daugherty commented on gene: TUBA1A: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 TH Louise Daugherty commented on gene: TH: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 SURF1 Louise Daugherty commented on gene: SURF1: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 SUCLG1 Louise Daugherty commented on gene: SUCLG1: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 SUCLA2 Louise Daugherty commented on gene: SUCLA2: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 SLC6A5 Louise Daugherty commented on gene: SLC6A5: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 SLC6A3 Louise Daugherty commented on gene: SLC6A3: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 SLC39A14 Louise Daugherty commented on gene: SLC39A14: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 SLC25A19 Louise Daugherty commented on gene: SLC25A19: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 SLC1A3 Louise Daugherty commented on gene: SLC1A3: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 SLC19A3 Louise Daugherty commented on gene: SLC19A3: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 SERAC1 Louise Daugherty commented on gene: SERAC1: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 SDHA Louise Daugherty commented on gene: SDHA: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 SCN8A Louise Daugherty commented on gene: SCN8A: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 SCN1A Louise Daugherty commented on gene: SCN1A: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 PDP1 Louise Daugherty commented on gene: PDP1: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 PDHA1 Louise Daugherty commented on gene: PDHA1: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 PDGFRB Louise Daugherty commented on gene: PDGFRB: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 PCCB Louise Daugherty commented on gene: PCCB: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 PCCA Louise Daugherty commented on gene: PCCA: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 OPA3 Louise Daugherty commented on gene: OPA3: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 OCLN Louise Daugherty commented on gene: OCLN: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 NKX6-2 Louise Daugherty commented on gene: NKX6-2: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 NDUFV1 Louise Daugherty commented on gene: NDUFV1: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 NDUFS8 Louise Daugherty commented on gene: NDUFS8: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 NDUFS7 Louise Daugherty commented on gene: NDUFS7: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 NDUFS4 Louise Daugherty commented on gene: NDUFS4: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 NDUFAF6 Louise Daugherty commented on gene: NDUFAF6: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 NDUFAF2 Louise Daugherty commented on gene: NDUFAF2: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 NDUFA10 Louise Daugherty commented on gene: NDUFA10: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 NDUFA1 Louise Daugherty commented on gene: NDUFA1: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 MUT Louise Daugherty commented on gene: MUT: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 MT-ND6 Louise Daugherty commented on gene: MT-ND6: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 MT-ND1 Louise Daugherty commented on gene: MT-ND1: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 MT-ATP6 Louise Daugherty commented on gene: MT-ATP6: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 MECR Louise Daugherty commented on gene: MECR: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 KCNQ3 Louise Daugherty commented on gene: KCNQ3: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 KCNQ2 Louise Daugherty commented on gene: KCNQ2: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 KCNA1 Louise Daugherty commented on gene: KCNA1: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 IVD Louise Daugherty commented on gene: IVD: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 ISG15 Louise Daugherty commented on gene: ISG15: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 IFIH1 Louise Daugherty commented on gene: IFIH1: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 HTRA2 Louise Daugherty commented on gene: HTRA2: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 HIBCH Louise Daugherty commented on gene: HIBCH: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 GNAO1 Louise Daugherty commented on gene: GNAO1: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 GLRB Louise Daugherty commented on gene: GLRB: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 GLRA1 Louise Daugherty commented on gene: GLRA1: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 GCDH Louise Daugherty commented on gene: GCDH: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 FOXP2 Louise Daugherty commented on gene: FOXP2: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 FA2H Louise Daugherty commented on gene: FA2H: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 ETHE1 Louise Daugherty commented on gene: ETHE1: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 DLAT Louise Daugherty commented on gene: DLAT: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 CSTB Louise Daugherty commented on gene: CSTB: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 COX15 Louise Daugherty commented on gene: COX15: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 COX10 Louise Daugherty commented on gene: COX10: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 COASY Louise Daugherty commented on gene: COASY: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 CACNB4 Louise Daugherty commented on gene: CACNB4: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 BCS1L Louise Daugherty commented on gene: BCS1L: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 BCAP31 Louise Daugherty commented on gene: BCAP31: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 AP1S2 Louise Daugherty commented on gene: AP1S2: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 ADCY5 Louise Daugherty commented on gene: ADCY5: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Adult onset movement disorder v0.99 ADAR Louise Daugherty commented on gene: ADAR: Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019
Genetic epilepsy syndromes v1.201 KCNJ11 Rebecca Foulger changed review comment from: Comment on mode of inheritance: Most KCNJ11 seizure patients have heterozygous variants but PMID:27181099 report a patient with a homozygous variant in KCNJ11 (p.F315I) and congenital hyperinsulinism. The authors say the patient had severe hypoglycemia and seizure following birth, but no further seizure details are given. OMIM disorder 'Diabetes, permanent neonatal, with or without neurologic features (MIM:606176) has both AR and AD inheritance recorded.; to: Comment on mode of inheritance: Most KCNJ11 seizure patients have heterozygous variants but PMID:27181099 report a patient with a homozygous variant in KCNJ11 (p.F315I) and congenital hyperinsulinism. The authors say the patient had severe hypoglycemia and seizure following birth, but no further seizure details are given. OMIM disorder 'Diabetes, permanent neonatal, with or without neurologic features (MIM:606176) has both AR and AD inheritance recorded. Therefore based on PMID:27181099 plus OMIM plu review by West Midlands, Oxford and Wessex GLH, have updated MOI from 'monoallelic' to 'BOTH monoallelic and biallelic'.
Genetic epilepsy syndromes v1.201 KCNJ11 Rebecca Foulger Mode of inheritance for gene: KCNJ11 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic epilepsy syndromes v1.200 KCNJ11 Rebecca Foulger changed review comment from: Comment on mode of inheritance: Most seizure patients have heterozygous variants but PMID:27181099 report a patient with a homozygous variant in KCNJ11 (p.F315I) and congenital hyperinsulinism. The authors say the patient had severe hypoglycemia and seizure following birth, but no further seizure details are given. OMIM disorder 'Diabetes, permanent neonatal, with or without neurologic features (MIM:606176) has both AR and AD inheritance recorded.; to: Comment on mode of inheritance: Most KCNJ11 seizure patients have heterozygous variants but PMID:27181099 report a patient with a homozygous variant in KCNJ11 (p.F315I) and congenital hyperinsulinism. The authors say the patient had severe hypoglycemia and seizure following birth, but no further seizure details are given. OMIM disorder 'Diabetes, permanent neonatal, with or without neurologic features (MIM:606176) has both AR and AD inheritance recorded.
Genetic epilepsy syndromes v1.200 KCNJ11 Rebecca Foulger changed review comment from: Comment on mode of inheritance: Most seizure patients have heterozygous variants but PMID:27181099 report a patient with a homozygous variant in KCNJ11 (p.F315I) and congenital hyperinsulinism. The authors say the patient had severe hypoglycemia and seizure following birth, but no further seizure details are given.; to: Comment on mode of inheritance: Most seizure patients have heterozygous variants but PMID:27181099 report a patient with a homozygous variant in KCNJ11 (p.F315I) and congenital hyperinsulinism. The authors say the patient had severe hypoglycemia and seizure following birth, but no further seizure details are given. OMIM disorder 'Diabetes, permanent neonatal, with or without neurologic features (MIM:606176) has both AR and AD inheritance recorded.
Genetic epilepsy syndromes v1.200 KCNJ11 Rebecca Foulger Publications for gene: KCNJ11 were set to 25678012; 16670688; 16609879; 27681997; 17065345; 28943513
Genetic epilepsy syndromes v1.199 KCNJ11 Rebecca Foulger Added comment: Comment on mode of inheritance: Most seizure patients have heterozygous variants but PMID:27181099 report a patient with a homozygous variant in KCNJ11 (p.F315I) and congenital hyperinsulinism. The authors say the patient had severe hypoglycemia and seizure following birth, but no further seizure details are given.
Genetic epilepsy syndromes v1.199 KCNJ11 Rebecca Foulger Mode of inheritance for gene: KCNJ11 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Adult onset movement disorder v0.98 YY1 James Polke edited their review of gene: YY1: Added comment: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming new Amber review (from Red) and flagged for further discssion with the GMS Neurology specialist test group: Gabriele-de Vries syndrome - phenotype variable - ?DISCUSS; Changed rating: AMBER
Adult onset movement disorder v0.98 WDR73 James Polke commented on gene: WDR73: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Galloway-Mowat syndrome 1 - onset and often death in infancy
Adult onset movement disorder v0.98 VAC14 James Polke commented on gene: VAC14: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Striatonigral degeneration (can include dystonia): onset in early childhood
Adult onset movement disorder v0.98 TUBA1A James Polke commented on gene: TUBA1A: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Lissencephaly 3 - not for this panel
Adult onset movement disorder v0.98 TH James Polke commented on gene: TH: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Segawa syndrome (onset in infancy of dopa-responsive dystonia): onset in infancy or early childhood
Adult onset movement disorder v0.98 SURF1 James Polke commented on gene: SURF1: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: CMT4K (childhood) and Leigh Syndrome (infancy)
Adult onset movement disorder v0.98 SUCLG1 James Polke commented on gene: SUCLG1: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Mitochondrial DNA depletion syndrome 9 (encephalomyopathic type with methylmalonic aciduria), onset in infancy
Adult onset movement disorder v0.98 SUCLA2 James Polke commented on gene: SUCLA2: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria) - onset in infancy
Adult onset movement disorder v0.98 SLC6A5 James Polke commented on gene: SLC6A5: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Hyperekplexia 3 onset in infancy
Adult onset movement disorder v0.98 SLC6A3 James Polke commented on gene: SLC6A3: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Infantile parkinsonism-dystonia (hyperkinesia with orolingual and limb dyskinesia, dystonia, and chorea, or hypokinesia with parkinsonian features, such as bradykinesia, rigidity, and tremor): onset in early infancy
Adult onset movement disorder v0.98 SLC39A14 James Polke commented on gene: SLC39A14: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Hypermanganesemia with dystonia 2 - onset in infancy or early childhood
Adult onset movement disorder v0.98 SLC25A19 James Polke commented on gene: SLC25A19: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Thiamine metabolism dysfunction syndrome 4 (progressive polyneuropathy type) onset in childhood, Microcephaly, Amish type - onset in infancy
Adult onset movement disorder v0.98 SLC1A3 James Polke commented on gene: SLC1A3: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Episodic ataxia 6 - onset in childhood, may be later - thought better on the ataxia panel
Adult onset movement disorder v0.98 SLC19A3 James Polke edited their review of gene: SLC19A3: Added comment: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming new Amber review (from Red) and flagged for further discssion with the GMS Neurology specialist test group: Thiamine metabolism dysfunction syndrome 2 (biotin- or thiamine-responsive encephalopathy type 2) - variable age of onset birth to adolesence, dystonia may persist after episodes have resolved ?DISCUSS; Changed rating: AMBER
Adult onset movement disorder v0.98 SERAC1 James Polke commented on gene: SERAC1: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome - onset in infancy/early childhood
Adult onset movement disorder v0.98 SDHA James Polke commented on gene: SDHA: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Mitochondrial phenotpye (LS) infancy/early childhood
Adult onset movement disorder v0.98 SCN8A James Polke commented on gene: SCN8A: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Number of epileptic phenotypes all early infancy/childhood onset
Adult onset movement disorder v0.98 SCN1A James Polke commented on gene: SCN1A: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Dravet's syndrome (onset in early childhood) FHM - ? Movement disorder
Adult onset movement disorder v0.98 PDP1 James Polke commented on gene: PDP1: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Pyruvate dehydrogenase phosphatase deficiency onset in infancy
Adult onset movement disorder v0.98 PDHA1 James Polke commented on gene: PDHA1: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Pyruvate dehydrogenase E1-alpha deficiency - onset in infancy/early childhood
Adult onset movement disorder v0.98 PDGFRB James Polke edited their review of gene: PDGFRB: Added comment: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming new Amber review (from Red) and flagged for further discssion with the GMS Neurology specialist test group: Basal ganglia calcification, idiopathic, 4 variable age of onset parkinsonism part of phenotype ?DISCUSS; Changed rating: AMBER
Adult onset movement disorder v0.98 PCCB James Polke commented on gene: PCCB: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Propionicacidemia - onset in 1st few weeks of life
Adult onset movement disorder v0.98 PCCA James Polke commented on gene: PCCA: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Propionicacidemia - onset in 1st few weeks of life
Adult onset movement disorder v0.98 OPA3 James Polke commented on gene: OPA3: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Optic atrophy with chorea and spastic paraplegia, infantile. Onset in infancy of optic atrophy, movement disorder later in childhood.
Adult onset movement disorder v0.98 OCLN James Polke commented on gene: OCLN: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Pseudo-TORCH syndrome 1 - onset in infancy/early childhood
Adult onset movement disorder v0.98 NKX6-2 James Polke commented on gene: NKX6-2: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Spastic ataxia-8 with hypomyelinating leukodystrophy (includes dystonia): onset in first year of life
Adult onset movement disorder v0.98 NDUFV1 James Polke commented on gene: NDUFV1: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Mitochondrial complex I deficiency, nuclear type 4 - onset in infancy
Adult onset movement disorder v0.98 NDUFS8 James Polke commented on gene: NDUFS8: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Mitochondrial complex I deficiency, nuclear type 2 onset early infancy/childhood
Adult onset movement disorder v0.98 NDUFS7 James Polke commented on gene: NDUFS7: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Mitochondrial complex I deficiency, nuclear type 3 onset in infancy
Adult onset movement disorder v0.98 NDUFS4 James Polke commented on gene: NDUFS4: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Mitochondrial complex I deficiency, nuclear type 1 onset in infancy
Adult onset movement disorder v0.98 NDUFAF6 James Polke commented on gene: NDUFAF6: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Mitochondrial complex I deficiency, nuclear type 17, onset in infancy or childhood
Adult onset movement disorder v0.98 NDUFAF2 James Polke commented on gene: NDUFAF2: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Mitochondrial complex I deficiency, nuclear type 10, onset in infancy or childhood
Adult onset movement disorder v0.98 NDUFA10 James Polke commented on gene: NDUFA10: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Mitochondrial complex I deficiency, nuclear type 22 - onset in infancy
Adult onset movement disorder v0.98 NDUFA1 James Polke commented on gene: NDUFA1: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Mitochondrial complex I deficiency - onset in first year of life
Adult onset movement disorder v0.98 MUT James Polke commented on gene: MUT: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Methylmalonic aciduria - not a movement disorder
Adult onset movement disorder v0.98 MT-ND6 James Polke commented on gene: MT-ND6: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: additonal review from Prof Huw Morris : I would suggest not including mitochondrial genes (although many can cause dystonia parkinsonsim) but rather including on the reports something along the lines:Concurrent CPEO, myopathy, neuropathy, optic atrophy may suggest a mitochondria disorder in a patient with ataxia, Parkinsonism or dystonia. Muscle biopsy, enzyme analysis and analysis of the mitochindrial gene panel may be useful
Adult onset movement disorder v0.98 MT-ND1 James Polke commented on gene: MT-ND1: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: additonal review from Prof Huw Morris : I would suggest not including mitochondrial genes (although many can cause dystonia parkinsonsim) but rather including on the reports something along the lines:Concurrent CPEO, myopathy, neuropathy, optic atrophy may suggest a mitochondria disorder in a patient with ataxia, Parkinsonism or dystonia. Muscle biopsy, enzyme analysis and analysis of the mitochindrial gene panel may be useful
Adult onset movement disorder v0.98 MT-ATP6 James Polke commented on gene: MT-ATP6: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: additonal review from Prof Huw Morris : I would suggest not including mitochondrial genes (although many can cause dystonia parkinsonsim) but rather including on the reports something along the lines:Concurrent CPEO, myopathy, neuropathy, optic atrophy may suggest a mitochondria disorder in a patient with ataxia, Parkinsonism or dystonia. Muscle biopsy, enzyme analysis and analysis of the mitochindrial gene panel may be useful
Adult onset movement disorder v0.98 MECR James Polke commented on gene: MECR: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalitie
Adult onset movement disorder v0.98 KCNQ3 James Polke commented on gene: KCNQ3: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Benign neonatal sizures
Adult onset movement disorder v0.98 KCNQ2 James Polke commented on gene: KCNQ2: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Epileptic encephalopathy, early infantile, benign neonatal seizures, myokymia
Adult onset movement disorder v0.98 KCNA1 James Polke commented on gene: KCNA1: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Episodic ataxia 1 onset in childhood
Adult onset movement disorder v0.98 IVD James Polke commented on gene: IVD: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Isovaleric acidemia - onset/death in infancy
Adult onset movement disorder v0.98 ISG15 James Polke commented on gene: ISG15: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Immunodeficiancy - not a movement disorder
Adult onset movement disorder v0.98 IFIH1 James Polke commented on gene: IFIH1: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Aicardi-Goutieres syndrome 7 (dystonia part of phenotype but onset in infancy/early childhood
Adult onset movement disorder v0.98 HTRA2 James Polke commented on gene: HTRA2: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: 3-methylglutaconic aciduria, type VIII (symptoms include extrapyramidal signs and dystonic posturing): Death in infancy
Adult onset movement disorder v0.98 HIBCH James Polke commented on gene: HIBCH: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: 3-hydroxyisobutryl-CoA hydrolase deficiency - onset in infancy
Adult onset movement disorder v0.98 GNAO1 James Polke commented on gene: GNAO1: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Neurodevelopmental disorder with involuntary movements (infantile or childhood onset of hyperkinetic involuntary movements, including chorea and athetosis)
Adult onset movement disorder v0.98 GLRB James Polke commented on gene: GLRB: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Hyperekplexia - onset in infancy
Adult onset movement disorder v0.98 GLRA1 James Polke commented on gene: GLRA1: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Hyperekplexia - onset in infancy
Adult onset movement disorder v0.98 GCDH James Polke commented on gene: GCDH: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Glutaric aciduria, type I (progressive movement disorder that usually begins during the first year of life)
Adult onset movement disorder v0.98 FOXP2 James Polke commented on gene: FOXP2: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Speech and language disorder
Adult onset movement disorder v0.98 FA2H James Polke commented on gene: FA2H: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Spastic paraplegia 35 (dystonia can be present): onset in childhood
Adult onset movement disorder v0.98 ETHE1 James Polke commented on gene: ETHE1: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Ethylmalonic encephalopathy - onset in first month of life
Adult onset movement disorder v0.98 DLAT James Polke commented on gene: DLAT: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Pyruvate dehydrogenase E2 deficiency (includes episodic dystonia, choreoathetoid movements): onset in infancy
Adult onset movement disorder v0.98 CSTB James Polke commented on gene: CSTB: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Progressive myoclonic epilepsy - most dodecmer expansion
Adult onset movement disorder v0.98 COX15 James Polke commented on gene: COX15: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Leigh syndrome - infancy/early childhood onset
Adult onset movement disorder v0.98 COX10 James Polke commented on gene: COX10: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: mitochondrial disorder - not a movement disorder
Adult onset movement disorder v0.98 COASY James Polke commented on gene: COASY: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Neurodegeneration with brain iron accumulation 6 (onset in infancy or early childhood)
Adult onset movement disorder v0.98 CACNB4 James Polke commented on gene: CACNB4: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Episodic ataxia 5 - I think we discussed as part of the ataxia panel and decided against including this as we have never reported any variants classified as more than a VUS
Adult onset movement disorder v0.98 BCS1L James Polke commented on gene: BCS1L: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: early childhood onset? Not a movement disorder
Adult onset movement disorder v0.98 BCAP31 James Polke commented on gene: BCAP31: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Deafness, dystonia and cerebral hypomyelination (DDCH): childhood onset
Adult onset movement disorder v0.98 AP1S2 James Polke commented on gene: AP1S2: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: onset in infancy - mental retardation syndrome
Adult onset movement disorder v0.98 ADCY5 James Polke commented on gene: ADCY5: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: Familial dyskinesia with facial myokymia: childhood onset (choreoathetosis, dystonia, myokymia)
Adult onset movement disorder v0.98 ADAR James Polke commented on gene: ADAR: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: AGS6 + dyschromatosis symmetrica hereditaria with dystonia: childhood onset
Severe early-onset obesity v1.15 GNAS Ivone Leong Phenotypes for gene: GNAS were changed from Congenital Obesity; Pseudohypoparathyroidism Ib, 603233; Pseudohypoparathyroidism Ic, 612462 to Congenital Obesity; Pseudohypoparathyroidism Ia, 103580; Pseudohypoparathyroidism Ib, 603233; Pseudohypoparathyroidism Ic, 612462
Lipoprotein lipase deficiency v1.0 Sarah Leigh promoted panel to version 1.0
Amyloidosis v0.7 APOA2 Eleanor Williams commented on gene: APOA2: Not associated with a relevant phenotype in OMIM but publications support association

4 cases reported:

PMID: 29270531 - Prokaeva et al 2017 - report a family with renal amyloidosis associated with a novel stop codon mutation in APOA2 and the apoA-II variant, 78Leuext21
PMID: 12787390 - Yazaki et al 2003 - a Caucasian man with progressive renal dysfunction found to have amyloidosis. DNA sequencing of the apoAII gene in the proband showed a T to C transition at the first position of the stop codon indicating replacement of the stop codon by l-arginine (Arg) at residue 78. DNA from other family members was not available.
PMID: 11401442 - Benson et al 2001 - report a family with hereditary renal amyloidosis. Sequence analysis of the apoAII gene of affected individuals showed heterozygosity for a single base substitution in the apoAII stop codon. The mutation results in extension of translation to the next in-frame stop codon 60 nucleotides downstream and is predicted to give a 21-residue C-terminal extension of the apoAII protein identical to that found in the amyloid.
PMID: 11703582 - Yazaki et al 2001 - Caucasian male with proteinuria and renal biopsy revealed amyloid deposition in glomeruli. DNA analysis revealed heterozygosity for a G to C transversion at the second position of the stop-codon of apoA-II gene, suggesting a stop to serine substitution at codon 78. Western blot analysis and amino acid sequence analysis of the patient's plasma apoA-II showed both normal apoA-II and variant apoA-II with a 21-amino acid residue extension at the C-terminus.
Adult onset movement disorder v0.97 ISCA-37468-Loss Louise Daugherty changed review comment from: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xls : 66 genes that LNGLH classified as red but which are green on the 100K panel. As you can see the majority are classified red due to their age of onset. There are a few which we felt did not fit the phenotype and 3 (which I have highlighted amber) that perhaps warrant more discussion.

Comment on list classification for the Region ISCA-37468-Loss : Red: MAOA/B deletion syndrome (stereotypical hand movements); to: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xls : 66 genes that LNGLH classified as red but which are green on the 100K panel. As you can see the majority are classified red due to their age of onset.
Comment on list classification for the Region ISCA-37468-Loss : Red: MAOA/B deletion syndrome (stereotypical hand movements)
Lipoprotein lipase deficiency v0.9 Sarah Leigh List of related panels changed from to R324
Panel types changed to GMS Rare Disease; GMS signed-off
Genetic epilepsy syndromes v1.198 TUBB2A Rebecca Foulger changed review comment from: Comment on list classification: Updated rating from Red to Green following advice from Helen Brittain: 3 unrelated cases from literature. Although not all with the genotype may develop seizures, there are sufficient cases of the epilepsy phenotype for inclusion on the panel.; to: Comment on list classification: Updated rating from Red to Green following advice from Helen Brittain: 3 unrelated cases from literature (two cases from PMID:24702957 and one from large-scale study PMID:25326637. Although not all with the genotype may develop seizures, there are sufficient cases of the epilepsy phenotype for inclusion on the panel.
Adult onset movement disorder v0.97 ISCA-37468-Loss Louise Daugherty changed review comment from: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xls : 66 genes that LNGLH classified as red but which are green on the 100K panel. As you can see the majority are classified red due to their age of onset. There are a few which we felt did not fit the phenotype and 3 (which I have highlighted amber) that perhaps warrant more discussion.

Comment on list classification for the Region ISCA-37468-Loss : Red: MAOA/B deletion syndrome (stereotypical hand movements); to: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xls : 66 genes that LNGLH classified as red but which are green on the 100K panel. As you can see the majority are classified red due to their age of onset. There are a few which we felt did not fit the phenotype and 3 (which I have highlighted amber) that perhaps warrant more discussion.

Comment on list classification for the Region ISCA-37468-Loss : Red: MAOA/B deletion syndrome (stereotypical hand movements)
Adult onset movement disorder v0.97 ISCA-37468-Loss Louise Daugherty changed review comment from: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xls : 66 genes that LNGLH classified as red but which are green on the 100K panel. As you can see the majority are classified red due to their age of onset. There are a few which we felt did not fit the phenotype and 3 (which I have highlighted amber) that perhaps warrant more discussion.

Comment on list classification for the Region ISCA-37468-Loss : MAOA/B deletion syndrome (stereotypical hand movements); to: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xls : 66 genes that LNGLH classified as red but which are green on the 100K panel. As you can see the majority are classified red due to their age of onset. There are a few which we felt did not fit the phenotype and 3 (which I have highlighted amber) that perhaps warrant more discussion.

Comment on list classification for the Region ISCA-37468-Loss : Red: MAOA/B deletion syndrome (stereotypical hand movements)
Adult onset movement disorder v0.97 ISCA-37468-Loss Louise Daugherty changed review comment from: Further follow up review by Robyn Labrum after webex call 26th July 2019 R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xls : 66 genes that LNGLH classified as red but which are green on the 100K panel. As you can see the majority are classified red due to their age of onset. There are a few which we felt did not fit the phenotype and 3 (which I have highlighted amber) that perhaps warrant more discussion.

Comment on list classification for the Region ISCA-37468-Loss : MAOA/B deletion syndrome (stereotypical hand movements); to: Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xls : 66 genes that LNGLH classified as red but which are green on the 100K panel. As you can see the majority are classified red due to their age of onset. There are a few which we felt did not fit the phenotype and 3 (which I have highlighted amber) that perhaps warrant more discussion.

Comment on list classification for the Region ISCA-37468-Loss : MAOA/B deletion syndrome (stereotypical hand movements)
Adult onset movement disorder v0.97 ISCA-37468-Loss Louise Daugherty commented on Region: ISCA-37468-Loss: Further follow up review by Robyn Labrum after webex call 26th July 2019 R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xls : 66 genes that LNGLH classified as red but which are green on the 100K panel. As you can see the majority are classified red due to their age of onset. There are a few which we felt did not fit the phenotype and 3 (which I have highlighted amber) that perhaps warrant more discussion.

Comment on list classification for the Region ISCA-37468-Loss : MAOA/B deletion syndrome (stereotypical hand movements)
Genetic epilepsy syndromes v1.198 HCN2 Rebecca Foulger changed review comment from: Comment on mode of inheritance: PMID:22131395: DiFrancesco et al. 2011 report a homozygous HCN2 variant (p.E515K) in a patient with idiopathic generalized epilepsy. Of 17 screened members of the same family, the proband was the only one affected and homozygous for the variant. This is the first evidence in humans for a single-point, homozygous loss-of-function mutation in HCN2 potentially associated with generalized epilepsy with recessive inheritance.; to: Comment on mode of inheritance: PMID:22131395: DiFrancesco et al. 2011 report a homozygous HCN2 variant (p.E515K) in a patient with idiopathic generalized epilepsy. Of 17 screened members of the same family, the proband was the only one affected and homozygous for the variant. This is the first evidence in humans for a single-point, homozygous loss-of-function mutation in HCN2 potentially associated with generalized epilepsy with recessive inheritance. Hence MOI listed as BOTH monoallelic and biallelic.
Amyloidosis v0.7 APOA1 Eleanor Williams commented on gene: APOA1: Associated with Amyloidosis, 3 or more types (#105200) in OMIM.
More than 3 cases reported.
Neuronal ceroid lipofuscinosis v0.8 ATP13A2 Sarah Leigh Publications for gene: ATP13A2 were set to
Neuronal ceroid lipofuscinosis v0.7 ATP13A2 Sarah Leigh Classified gene: ATP13A2 as Green List (high evidence)
Neuronal ceroid lipofuscinosis v0.7 ATP13A2 Sarah Leigh Added comment: Comment on list classification: Comments from Dr Clare E Beesley, Clinical Scientist, London North Genomic Laboratory Hub, Great Ormond Street Hospital for Children NHS Foundation Trust: we specified amber on the NCL panel because there was only one reported family that had storage inclusions consistent with NCL (PMID 22388936) and there is a terrier dog model with similar features (PMID 21362476). However, it’s possible that patients with Kufor-Rakeb have storage inclusions consistent with NCL, but they’ve just not been investigated. There is plenty of evidence for it to be green for Kufor-Rakeb syndrome in the undiagnosed metabolic disorders panel (https://panelapp.genomicsengland.co.uk/panels/302/gene/ATP13A2), so, for consistency, we would be happy for it to be promoted to green for the NCL panel.
Neuronal ceroid lipofuscinosis v0.7 ATP13A2 Sarah Leigh Gene: atp13a2 has been classified as Green List (High Evidence).
Severe early-onset obesity v1.14 GNAS Ivone Leong Phenotypes for gene: GNAS were changed from Congenital Obesity; Pseudopseudohypoparathyroidism, 612463 to Congenital Obesity; Pseudohypoparathyroidism Ib, 603233; Pseudohypoparathyroidism Ic, 612462
Lysosomal storage disorder v0.8 HYAL1 Sarah Leigh Classified gene: HYAL1 as Green List (high evidence)
Lysosomal storage disorder v0.8 HYAL1 Sarah Leigh Added comment: Comment on list classification: Comments from Dr Clare E Beesley, Clinical Scientist, London North Genomic Laboratory Hub, Great Ormond Street Hospital for Children NHS Foundation Trust: 2 unrelated families that have variants (PMIDs 10339581, 21559944), also have a confirmed enzyme diagnosis and there is a mouse model that shows similar features (PMID 26322170).
Lysosomal storage disorder v0.8 HYAL1 Sarah Leigh Gene: hyal1 has been classified as Green List (High Evidence).
Lysosomal storage disorder v0.7 HYAL1 Sarah Leigh Publications for gene: HYAL1 were set to
Severe early-onset obesity v1.13 GNAS Ivone Leong Phenotypes for gene: GNAS were changed from Congenital Obesity; Pseudohypoparathyroidism, 612463 to Congenital Obesity; Pseudopseudohypoparathyroidism, 612463
Severe early-onset obesity v1.12 GNAS Ivone Leong Phenotypes for gene: GNAS were changed from Congenital Obesity; Pseudopseudohypoparathyroidism, 612463 to Congenital Obesity; Pseudohypoparathyroidism, 612463
Severe early-onset obesity v1.11 GNAS Ivone Leong Phenotypes for gene: GNAS were changed from Congenital Obesity to Congenital Obesity; Pseudopseudohypoparathyroidism, 612463
Adult solid tumours cancer susceptibility v1.7 VHL Ivone Leong Phenotypes for gene: VHL were changed from Familial Paraganglioma and Pheochromocytoma to Familial Paraganglioma and Pheochromocytoma; VON HIPPEL-LINDAU (VHL) SYNDROME, 193300
Amyloidosis v0.7 B2M Eleanor Williams commented on gene: B2M: Provisionally associated with ?Amyloidosis, familial visceral (#105200) in OMIM.

PMID: 22693999 - Valleix et al 2012 - report a French family with 4 members who had progressive bowel dysfunction with extensive visceral amyloid deposits composed of β2-microglobulin. All the members of this family had normal circulating concentrations of β2-microglobulin and normal renal function. A heterozygous mutation in the B2M gene was found in each of the affected family members c.286G→A, Asp76Asn. The 3 unaffected family members tested were all wild type. The Asp76Asn β2-microglobulin variant was thermodynamically unstable and remarkably fibrillogenic in vitro under physiological conditions.
Childhood solid tumours cancer susceptibility v1.5 VHL Ivone Leong Phenotypes for gene: VHL were changed from Familial Paraganglioma and Pheochromocytoma to Familial Paraganglioma and Pheochromocytoma; VON HIPPEL-LINDAU (VHL) SYNDROME, 193300
Inborn errors of metabolism v1.113 DHODH Sarah Leigh Classified gene: DHODH as Green List (high evidence)
Inborn errors of metabolism v1.113 DHODH Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 11 variants reported in 6 families (PMID 19915526), together with a knockout mouse model (PMID 27626380).
Inborn errors of metabolism v1.113 DHODH Sarah Leigh Gene: dhodh has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.112 DHODH Sarah Leigh Publications for gene: DHODH were set to 27604308
Inborn errors of metabolism v1.111 DHODH Sarah Leigh Added comment: Comment on phenotypes: Unexplained skeletal dysplasia;Bilateral microtia;Deafness and congenital structural abnormalities;Dihydroorotate dehydrogenase deficiency (Disorders of pyrimidine metabolism)
Inborn errors of metabolism v1.111 DHODH Sarah Leigh Phenotypes for gene: DHODH were changed from Unexplained skeletal dysplasia; Bilateral microtia; Deafness and congenital structural abnormalities; Dihydroorotate dehydrogenase deficiency (Disorders of pyrimidine metabolism) to Miller syndrome 263750
Inborn errors of metabolism v1.110 DHDDS Sarah Leigh Phenotypes for gene: DHDDS were changed from Retinitis pigmentosa 59 613861; Posterior segment abnormalities; Retinitis pigmentosa (other congenital disorders of glycosylation) to ?Congenital disorder of glycosylation, type 1bb 613861; Developmental delay and seizures with or without movement abnormalities 617836; Retinitis pigmentosa 59 613861
Inborn errors of metabolism v1.109 DHCR24 Sarah Leigh Deleted their comment
Inborn errors of metabolism v1.109 DHCR24 Sarah Leigh Classified gene: DHCR24 as Green List (high evidence)
Inborn errors of metabolism v1.109 DHCR24 Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 7 variants reported in at least cases, two of the variants were in cis in a case which was compound heterozygous with another variant (PMID 11519011). Supportive functional studies were also presented.
Inborn errors of metabolism v1.109 DHCR24 Sarah Leigh Gene: dhcr24 has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.109 DHCR24 Sarah Leigh Classified gene: DHCR24 as Green List (high evidence)
Inborn errors of metabolism v1.109 DHCR24 Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 7 variants reported in at least cases, two of the variants were in cis in a case which was compound heterozygous with another variant (PMID 11519011). Supportive functional studies were also presented.
Inborn errors of metabolism v1.109 DHCR24 Sarah Leigh Gene: dhcr24 has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.108 DHCR24 Sarah Leigh Publications for gene: DHCR24 were set to 27604308
Inborn errors of metabolism v1.107 DHCR24 Sarah Leigh Added comment: Comment on phenotypes: Desmosterolosis (Disorders of sterol biosynthesis);Unexplained skeletal dysplasia;Intellectual disability
Inborn errors of metabolism v1.107 DHCR24 Sarah Leigh Phenotypes for gene: DHCR24 were changed from Desmosterolosis (Disorders of sterol biosynthesis); Unexplained skeletal dysplasia; Intellectual disability to Desmosterolosis 602398
Inborn errors of metabolism v1.106 DCXR Sarah Leigh Publications for gene: DCXR were set to 27604308; 22042873; 23988570
Inborn errors of metabolism v1.105 DCXR Sarah Leigh Publications for gene: DCXR were set to 27604308; 22042873; 23988570
Inborn errors of metabolism v1.105 DCXR Sarah Leigh Publications for gene: DCXR were set to 27604308; 22042873
Inborn errors of metabolism v1.104 DCXR Sarah Leigh Classified gene: DCXR as Green List (high evidence)
Inborn errors of metabolism v1.104 DCXR Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with phenotype in OMIM and not in Gen2Phen. At least 2 variants identified within Ashkenazi Jewish population, that functional studies have shown to be loss of function variants that result in lack of the normal DCXR protein.
Inborn errors of metabolism v1.104 DCXR Sarah Leigh Gene: dcxr has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.103 DCXR Sarah Leigh changed review comment from: Comment on phenotypes: Essential pentosuria (Disorders of pentose metabolism) is a benign inborn error of metabolism, in which 1 to 4 gm of the pentose L-xylulose is excreted in the urine each day, as a result some patients maybe treated for diabetes mellitus with insulin (PMID 22042873).; to: Comment on phenotypes: Essential pentosuria (Disorders of pentose metabolism) is a benign inborn error of metabolism, in which 1 to 4 gm of the pentose L-xylulose is excreted in the urine each day, as a result some patients maybe treated inappropriately for diabetes mellitus with insulin (PMID 22042873).
Inborn errors of metabolism v1.103 DCXR Sarah Leigh Added comment: Comment on phenotypes: Essential pentosuria (Disorders of pentose metabolism) is a benign inborn error of metabolism, in which 1 to 4 gm of the pentose L-xylulose is excreted in the urine each day, as a result some patients maybe treated for diabetes mellitus with insulin (PMID 22042873).
Inborn errors of metabolism v1.103 DCXR Sarah Leigh Phenotypes for gene: DCXR were changed from [Pentosuria] 260800; Essential pentosuria (Disorders of pentose metabolism) to [Pentosuria] 260800
Inborn errors of metabolism v1.102 DCXR Sarah Leigh Publications for gene: DCXR were set to 27604308
Inborn errors of metabolism v1.101 CYP7B1 Sarah Leigh changed review comment from: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with phenotype in OMIM and not in Gen2Phen. At least 10 variants identified in unrelated cases of Spastic paraplegia 5A, autosomal recessive 270800 and one of these also had Bile acid synthesis defect, congenital, 3 613812.; to: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with phenotype in OMIM and not in Gen2Phen. At least 10 variants identified in unrelated cases of Spastic paraplegia 5A, autosomal recessive 270800 and one of these variants was also found in a case of Bile acid synthesis defect, congenital, 3 613812.
Inborn errors of metabolism v1.101 CYP7B1 Sarah Leigh Publications for gene: CYP7B1 were set to 27604308; 9802883
Inborn errors of metabolism v1.100 CYP7B1 Sarah Leigh Classified gene: CYP7B1 as Green List (high evidence)
Inborn errors of metabolism v1.100 CYP7B1 Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with phenotype in OMIM and not in Gen2Phen. At least 10 variants identified in unrelated cases of Spastic paraplegia 5A, autosomal recessive 270800 and one of these also had Bile acid synthesis defect, congenital, 3 613812.
Inborn errors of metabolism v1.100 CYP7B1 Sarah Leigh Gene: cyp7b1 has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.99 CYP7B1 Sarah Leigh Phenotypes for gene: CYP7B1 were changed from Bile acid synthesis defect, congenital, 3 to Bile acid synthesis defect, congenital, 3 613812; Spastic paraplegia 5A, autosomal recessive 270800
Inborn errors of metabolism v1.98 CTSC Sarah Leigh Classified gene: CTSC as Green List (high evidence)
Inborn errors of metabolism v1.98 CTSC Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with phenotype in OMIM and not in Gen2Phen. At least 13 variants identified in unrelated cases of Papillon-Lefevre syndrome 245000.
Inborn errors of metabolism v1.98 CTSC Sarah Leigh Gene: ctsc has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.97 CTSC Sarah Leigh Added comment: Comment on phenotypes: Papillon-Lef vre syndrome (Other lysosomal disorders, Cathepsin-related disorders);Unexplained skeletal dysplasia
Inborn errors of metabolism v1.97 CTSC Sarah Leigh Phenotypes for gene: CTSC were changed from Papillon-Lef vre syndrome (Other lysosomal disorders, Cathepsin-related disorders); Unexplained skeletal dysplasia to Haim-Munk syndrome 245010; Papillon-Lefevre syndrome 245000; Periodontitis 1, juvenile 170650
Limb disorders v1.56 EPHA4 Eleanor Williams commented on gene: EPHA4: EPHA4 not associated with any phenotype in OMIM or Gene2Phenotype.

PMID: 25959774 - Lupiáñez et al 2015 - studied limb abnormalities in 3 sets of families:
Group 1 - 3 unrelated families with a dominantly inherited novel type of brachydactyly, characterized by short digits predominantly on the preaxial (radial) side resulting in stub thumbs, short index fingers and a cutaneous web between the first and second fingers. aCGH revealed heterozygous deletions of 1.75–1.9 Mb on chromosome 2q35–36 in all three affected families. All three deletions include the EPHA4 gene along with a large portion of its surrounding TAD and extend into the non-coding part of the adjacent PAX3 TAD (topologically associated domain), thereby removing the predicted boundary between the EPHA4 and PAX3 TADs. Mutant mice with a deletion corresponding to the human disease alleles recapitulated the phenotype observed in patients.
Group 2 - 2 unrelated families with F-syndrome, a limb malformation syndrome characterized by severe and complex syndactyly, often involving the first and second fingers, and polydactyly of the feet. By whole genome sequencing they detected a ~1.1 Mb heterozygous inversion in family F1 and a ~1.4 Mb heterozygous duplication, arranged in direct tandem orientation, in family F2. The telomeric breakpoints were located 1.4 Mb away from the EPHA4 gene within the gene desert in the case of the inversion, and 1.2 Mb in the case of the duplication. Heterozygous as well as homozygous newborn mice generated via tetraploid aggregation died shortly after birth of unknown cause and did not show overt limb phenotypes or other morphological defects
Group 3 - a family that carries a heterozygous ~900 kb duplication in chromosomal region 2q35 that results in severe polysyndactyly and craniofacial abnormalities. The phenotype is reminiscent of the doublefoot (Dbf) mouse mutant, which also features massive polysyndactyly and was shown to be caused by a ~600 kb deletion affecting the same region (Babbs et al., 2008)
Using 4C-seq they show that In wild-type distal limbs, there was minimal interaction of Pax3, Wnt6 and Ihh with non-coding sequences in the Epha4 TAD. In contrast, all three genes showed substantial interaction with the Epha4 TAD in the mutants. Similar results were found using patient fibroblasts.

Genomic re-arrangements in the Epha4 TAD can result in limb abnormalities. It maybe best to represent these as regions of gain or loss in PanelApp
Inborn errors of metabolism v1.96 CSTB Sarah Leigh Added comment: Comment on phenotypes: Intellectual disability;Myoclonic epilepsy of Unverricht and Lundborg (Other metabolic disorders)
Inborn errors of metabolism v1.96 CSTB Sarah Leigh Phenotypes for gene: CSTB were changed from Intellectual disability; Myoclonic epilepsy of Unverricht and Lundborg (Other metabolic disorders) to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg) 254800
Inborn errors of metabolism v1.95 CLDN19 Sarah Leigh Added comment: Comment on phenotypes: Hypomagnesaemia type 5, renal with ocular involvement (Disorder of magnesium metabolism);Renal tract calcification (or Nephrolithiasis/nephrocalcinosis)
Inborn errors of metabolism v1.95 CLDN19 Sarah Leigh Phenotypes for gene: CLDN19 were changed from Hypomagnesaemia type 5, renal with ocular involvement (Disorder of magnesium metabolism); Renal tract calcification (or Nephrolithiasis/nephrocalcinosis) to Hypomagnesemia 5, renal, with ocular involvement 248190
Inborn errors of metabolism v1.95 CLDN19 Sarah Leigh Publications for gene: CLDN19 were set to 27604308; 22422540; 17033971
Inborn errors of metabolism v1.94 CLDN19 Sarah Leigh Publications for gene: CLDN19 were set to 27604308
Inborn errors of metabolism v1.93 CLDN19 Sarah Leigh Classified gene: CLDN19 as Green List (high evidence)
Inborn errors of metabolism v1.93 CLDN19 Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 5 variants reported in at least 6 unrelated cases.
Inborn errors of metabolism v1.93 CLDN19 Sarah Leigh Gene: cldn19 has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.92 CLDN16 Sarah Leigh Classified gene: CLDN16 as Green List (high evidence)
Inborn errors of metabolism v1.92 CLDN16 Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with phenotype in OMIM and not in Gen2Phen. At least 19 variants identified in unrelated cases.
Inborn errors of metabolism v1.92 CLDN16 Sarah Leigh Gene: cldn16 has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.91 CLDN16 Sarah Leigh Added comment: Comment on phenotypes: Renal tract calcification (or Nephrolithiasis/nephrocalcinosis);Hypomagnesaemia type 3, renal (Disorder of magnesium metabolism)
Inborn errors of metabolism v1.91 CLDN16 Sarah Leigh Phenotypes for gene: CLDN16 were changed from Renal tract calcification (or Nephrolithiasis/nephrocalcinosis); Hypomagnesaemia type 3, renal (Disorder of magnesium metabolism) to Hypomagnesemia 3, renal 248250
Inborn errors of metabolism v1.90 CISD2 Sarah Leigh Classified gene: CISD2 as Green List (high evidence)
Inborn errors of metabolism v1.90 CISD2 Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM and as both RD and IF Gen2Phen gene. At least 3 variants reported in unrelated cases, together with segration and functional studies.
Inborn errors of metabolism v1.90 CISD2 Sarah Leigh Gene: cisd2 has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.89 CISD2 Sarah Leigh Publications for gene: CISD2 were set to 27604308; 17846994; 25056293; 25371195; 29237418
Inborn errors of metabolism v1.89 CISD2 Sarah Leigh Publications for gene: CISD2 were set to 27604308
Inborn errors of metabolism v1.88 CISD2 Sarah Leigh Added comment: Comment on phenotypes: Diabetes with additional phenotypes suggestive of a monogenic aetiology;Wolfram syndrome 2 (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Intellectual disability
Inborn errors of metabolism v1.88 CISD2 Sarah Leigh Phenotypes for gene: CISD2 were changed from Diabetes with additional phenotypes suggestive of a monogenic aetiology; Wolfram syndrome 2 (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Intellectual disability to Wolfram syndrome 2 604928
Severe early-onset obesity v1.10 CEP290 Ivone Leong Phenotypes for gene: CEP290 were changed from Congenital Obesity to Congenital Obesity; ?Bardet-Biedl syndrome 14, 615991
Severe early-onset obesity v1.9 CEP290 Ivone Leong Mode of inheritance for gene: CEP290 was changed from to BIALLELIC, autosomal or pseudoautosomal
Inborn errors of metabolism v1.87 ASAH1 Sarah Leigh changed review comment from: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 7 variants reported in 6 cases of Farber lipogranulomatosis 228000 and 5 variants in 3 cases of Spinal muscular atrophy with progressive myoclonic epilepsy 159950.; to: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 7 variants reported in 6 cases of Farber lipogranulomatosis 228000 and 5 variants in 3 cases of Spinal muscular atrophy with progressive myoclonic epilepsy 159950.
Inborn errors of metabolism v1.87 APOB Sarah Leigh changed review comment from: Comment on list classification: At least 5 variants associated with Hypobetalipoproteinemia 615558 without other variants in other genes and 2 variants associated with Hypercholesterolemia, familial, 2 144010 in numberous cases.; to: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with phenotype in OMIM and not in Gen2Phen. At least 5 variants associated with Hypobetalipoproteinemia 615558 without other variants in other genes and 2 variants associated with Hypercholesterolemia, familial, 2 144010 in numberous cases.
Inborn errors of metabolism v1.87 APOB Sarah Leigh Classified gene: APOB as Green List (high evidence)
Inborn errors of metabolism v1.87 APOB Sarah Leigh Added comment: Comment on list classification: At least 5 variants associated with Hypobetalipoproteinemia 615558 without other variants in other genes and 2 variants associated with Hypercholesterolemia, familial, 2 144010 in numberous cases.
Inborn errors of metabolism v1.87 APOB Sarah Leigh Gene: apob has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.86 APOB Sarah Leigh Phenotypes for gene: APOB were changed from Familial hypobetalipoproteinaemia (Inherited hypolipidaemias); Familial hypercholesterolaemia to Hypercholesterolemia, familial, 2 144010; Hypobetalipoproteinemia 615558
Inborn errors of metabolism v1.85 ALPL Sarah Leigh changed review comment from: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 16 variants reported in hypophosphatasia, infantile 241500, some of these variants and others were found in childhood and adult Hypophosphatasia and two addtional variants were reported in a case of perinatal lethal hypophosphatasia (PMID 11745997).; to: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 16 variants reported in hypophosphatasia, infantile 241500, some of these variants and others were found in childhood and adult Hypophosphatasia and two addtional variants were reported in a case of perinatal lethal hypophosphatasia (PMID 11745997).
Inborn errors of metabolism v1.85 ALG13 Sarah Leigh changed review comment from: Comment on list classification: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 2 variants reported, one of which (c.320A>G, p.N107S) is associated with Epileptic encephalopathy, early infantile, 36 300884 as a de novo variant in at least 6 unrelated cases, athough the conection with Congenital disorder of glycosylation, type Is 300884 is not clear from these cases. The second variant was reported in an infant who died at age 1 year. Transferrin isoelectric focusing showed abnormal N-glycosylation and was consistent with a diagnostic classification of congenital disorder of glycosylation type Is (CDG1S). Studies of patient-derived cells showed decreased enzyme activity, at about 17% of wildtype (PMID 22492991).; to: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 2 variants reported, one of which (c.320A>G, p.N107S) is associated with Epileptic encephalopathy, early infantile, 36 300884 as a de novo variant in at least 6 unrelated cases, athough the conection with Congenital disorder of glycosylation, type Is 300884 is not clear from these cases. The second variant was reported in an infant who died at age 1 year. Transferrin isoelectric focusing showed abnormal N-glycosylation and was consistent with a diagnostic classification of congenital disorder of glycosylation type Is (CDG1S). Studies of patient-derived cells showed decreased enzyme activity, at about 17% of wildtype (PMID 22492991).
Inborn errors of metabolism v1.85 ALPL Sarah Leigh Publications for gene: ALPL were set to 27604308; 11745997; 1409720; 17213282
Inborn errors of metabolism v1.84 ALPL Sarah Leigh Publications for gene: ALPL were set to 27604308; 11745997; 1409720; 17213282
Inborn errors of metabolism v1.84 ALPL Sarah Leigh Publications for gene: ALPL were set to 27604308
Inborn errors of metabolism v1.83 ALPL Sarah Leigh Classified gene: ALPL as Green List (high evidence)
Inborn errors of metabolism v1.83 ALPL Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 16 variants reported in hypophosphatasia, infantile 241500, some of these variants and others were found in childhood and adult Hypophosphatasia and two addtional variants were reported in a case of perinatal lethal hypophosphatasia (PMID 11745997).
Inborn errors of metabolism v1.83 ALPL Sarah Leigh Gene: alpl has been classified as Green List (High Evidence).
Inborn errors of metabolism v1.82 ALPL Sarah Leigh Phenotypes for gene: ALPL were changed from Unexplained skeletal dysplasia; Osteogenesis Imperfecta; Craniosynostosis syndromes phenotypes; Hypophosphatasia (Disorders of pyridoxine metabolism) to Hypophosphatasia, adult 146300; Hypophosphatasia, childhood 241510; Hypophosphatasia, infantile241500; Odontohypophosphatasia 146300
Inborn errors of metabolism v1.81 ALG13 Sarah Leigh Classified gene: ALG13 as Amber List (moderate evidence)
Inborn errors of metabolism v1.81 ALG13 Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 2 variants reported, one of which (c.320A>G, p.N107S) is associated with Epileptic encephalopathy, early infantile, 36 300884 as a de novo variant in at least 6 unrelated cases, athough the conection with Congenital disorder of glycosylation, type Is 300884 is not clear from these cases. The second variant was reported in an infant who died at age 1 year. Transferrin isoelectric focusing showed abnormal N-glycosylation and was consistent with a diagnostic classification of congenital disorder of glycosylation type Is (CDG1S). Studies of patient-derived cells showed decreased enzyme activity, at about 17% of wildtype (PMID 22492991).
Inborn errors of metabolism v1.81 ALG13 Sarah Leigh Gene: alg13 has been classified as Amber List (Moderate Evidence).
Pancreatitis v1.12 Ivone Leong List of related panels changed from to R175
Polycystic liver disease interim v0.6 Ivone Leong List of related panels changed from to R173
Cholestasis v0.24 Ivone Leong List of related panels changed from to R171
Intestinal failure v0.31 Ivone Leong List of related panels changed from to R331
Non-acute porphyrias v0.13 Ivone Leong List of related panels changed from to R168
Malformations of cortical development v1.171 EMX2 Louise Daugherty Classified gene: EMX2 as Green List (high evidence)
Malformations of cortical development v1.171 EMX2 Louise Daugherty Gene: emx2 has been classified as Green List (High Evidence).
Malformations of cortical development v1.170 EMX2 Louise Daugherty changed review comment from: From review Rebecca Foulger (Genomics England curator) [email protected]
Review from Genetic epilepsy syndromes panel:
Comment on list classification: Updated rating from Amber to Green: Green review by Zornitza and 3 cases of Schizencephaly patients with EMX2 variants and partial epilepsy in PMID:9359037. PMID:15921232 (2005) report that half of Schizencephaly patients show epilepsy. Therefore sufficient evidence for inclusion on panel.
Created: 29 Nov 2018, 11:05 a.m.

Faiella et al., 1997 (PMID:9359037) summarise 10 patients with Schizencephaly. 6 patients were heterozygous for de novo variants in EMX2 (including 2 brothers). 3 of these unrelated patients have partial epilepsy (patients VF, MB and PB).
Created: 29 Nov 2018, 11:03 a.m. | Last Modified: 22 Jul 2019, 12:16 p.m.

Panel Version: 1.173; to: From review Rebecca Foulger (Genomics England curator) Review from Genetic epilepsy syndromes panel:
Comment on list classification: Updated rating from Amber to Green: Green review by Zornitza and 3 cases of Schizencephaly patients with EMX2 variants and partial epilepsy in PMID:9359037. PMID:15921232 (2005) report that half of Schizencephaly patients show epilepsy. Therefore sufficient evidence for inclusion on panel.
Created: 29 Nov 2018, 11:05 a.m.

Faiella et al., 1997 (PMID:9359037) summarise 10 patients with Schizencephaly. 6 patients were heterozygous for de novo variants in EMX2 (including 2 brothers). 3 of these unrelated patients have partial epilepsy (patients VF, MB and PB).
Created: 29 Nov 2018, 11:03 a.m. | Last Modified: 22 Jul 2019, 12:16 p.m.

Panel Version: 1.173
Malformations of cortical development v1.170 EMX2 Louise Daugherty changed review comment from: From review
Rebecca Foulger (Genomics England curator)
[email protected]
I don't know

Review from Genetic epilepsy syndromes panel:

Comment on list classification: Updated rating from Amber to Green: Green review by Zornitza and 3 cases of Schizencephaly patients with EMX2 variants and partial epilepsy in PMID:9359037. PMID:15921232 (2005) report that half of Schizencephaly patients show epilepsy. Therefore sufficient evidence for inclusion on panel.
Created: 29 Nov 2018, 11:05 a.m.

Faiella et al., 1997 (PMID:9359037) summarise 10 patients with Schizencephaly. 6 patients were heterozygous for de novo variants in EMX2 (including 2 brothers). 3 of these unrelated patients have partial epilepsy (patients VF, MB and PB).
Created: 29 Nov 2018, 11:03 a.m. | Last Modified: 22 Jul 2019, 12:16 p.m.

Panel Version: 1.173; to: From review Rebecca Foulger (Genomics England curator) [email protected]
Review from Genetic epilepsy syndromes panel:
Comment on list classification: Updated rating from Amber to Green: Green review by Zornitza and 3 cases of Schizencephaly patients with EMX2 variants and partial epilepsy in PMID:9359037. PMID:15921232 (2005) report that half of Schizencephaly patients show epilepsy. Therefore sufficient evidence for inclusion on panel.
Created: 29 Nov 2018, 11:05 a.m.

Faiella et al., 1997 (PMID:9359037) summarise 10 patients with Schizencephaly. 6 patients were heterozygous for de novo variants in EMX2 (including 2 brothers). 3 of these unrelated patients have partial epilepsy (patients VF, MB and PB).
Created: 29 Nov 2018, 11:03 a.m. | Last Modified: 22 Jul 2019, 12:16 p.m.

Panel Version: 1.173
Malformations of cortical development v1.170 EMX2 Louise Daugherty commented on gene: EMX2: From review
Rebecca Foulger (Genomics England curator)
[email protected]
I don't know

Review from Genetic epilepsy syndromes panel:

Comment on list classification: Updated rating from Amber to Green: Green review by Zornitza and 3 cases of Schizencephaly patients with EMX2 variants and partial epilepsy in PMID:9359037. PMID:15921232 (2005) report that half of Schizencephaly patients show epilepsy. Therefore sufficient evidence for inclusion on panel.
Created: 29 Nov 2018, 11:05 a.m.

Faiella et al., 1997 (PMID:9359037) summarise 10 patients with Schizencephaly. 6 patients were heterozygous for de novo variants in EMX2 (including 2 brothers). 3 of these unrelated patients have partial epilepsy (patients VF, MB and PB).
Created: 29 Nov 2018, 11:03 a.m. | Last Modified: 22 Jul 2019, 12:16 p.m.

Panel Version: 1.173
Fetal anomalies v0.337 MITF Rebecca Foulger changed review comment from: Kept rating as Amber on advice from Anna de Burca (Genomics England Clinical Team): fetally releavant phenotype but insufficient evidence for Green rating.; to: Kept rating as Amber on advice from Anna de Burca (Genomics England Clinical Team): fetally relevant phenotype but insufficient evidence for Green rating.
Malformations of cortical development v1.170 EMX2 Louise Daugherty gene: EMX2 was added
gene: EMX2 was added to Malformations of cortical development. Sources: Other
Mode of inheritance for gene: EMX2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: EMX2 were set to 8528262; 9359037
Phenotypes for gene: EMX2 were set to Schizencephaly, 269160
Review for gene: EMX2 was set to GREEN
Added comment: Due to a webex to discuss R59 (https://panelapp.genomicsengland.co.uk/panels/489/) on Aug 8th 2019 (RF, EM, RS with WWMGLH), some discussion points overlapped with additional panels and it was agreed that EMX2 should be added to the : Malformations of cortical development panel : https://panelapp.genomicsengland.co.uk/panels/96/ which a component of the GMS Super panels: https://panelapp.genomicsengland.co.uk/panels/96/ and Cerebral malformations (https://panelapp.genomicsengland.co.uk/panels/491/).
Phenotype is: Schizencephaly
Sources: Other
Inborn errors of metabolism v1.80 ALG13 Sarah Leigh Phenotypes for gene: ALG13 were changed from Intellectual disability; Epileptic encephalopathy; ALG13-CDG (Disorders of protein N-glycosylation); Epileptic encephalopathy, early infantile, 36 300884 to ?Congenital disorder of glycosylation, type Is 300884; Epileptic encephalopathy, early infantile, 36 300884
Congenital disorders of glycosylation v1.27 ALG13 Sarah Leigh Added comment: Comment on mode of inheritance: From OMIM and Gen2Phen
Congenital disorders of glycosylation v1.27 ALG13 Sarah Leigh Mode of inheritance for gene: ALG13 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Fetal anomalies v0.337 TGFB1 Rebecca Foulger edited their review of gene: TGFB1: Changed rating: RED
Fetal anomalies v0.337 TERT Rebecca Foulger edited their review of gene: TERT: Changed rating: RED
Fetal anomalies v0.337 SASS6 Rebecca Foulger Classified gene: SASS6 as Amber List (moderate evidence)
Fetal anomalies v0.337 SASS6 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Amber to match 'possible' Disease confidence rating in PAGE Additional genes list. Note that SASS6 is not currently associated with a disorder in Gene2Phenotype. Associated with OMIM disorder: ?Microcephaly 14, primary, autosomal recessive, 616402' based on 1 reported family.
Fetal anomalies v0.337 SASS6 Rebecca Foulger Gene: sass6 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.336 PDHB Rebecca Foulger commented on gene: PDHB
Fetal anomalies v0.336 PDHB Rebecca Foulger Phenotypes for gene: PDHB were changed from Pyruvate dehydrogenase E1-beta deficiency to Pyruvate dehydrogenase E1-beta deficiency, 614111
Congenital myopathy v1.161 MICU1 Louise Daugherty Phenotypes for gene: MICU1 were changed from Myopathy with extrapyramidal signs, 615673 (3) to Myopathy with extrapyramidal signs, 615673
Congenital myopathy v1.160 FAM111B Louise Daugherty Phenotypes for gene: FAM111B were changed from Poikiloderma, hereditary fibrosing, with tendon contractures, myopathy, and pulmonaryfibrosis, 615704 (3) to Poikiloderma, hereditary fibrosing, with tendon contractures, myopathy, and pulmonaryfibrosis, 615704
Congenital myopathy v1.159 KLHL41 Louise Daugherty Phenotypes for gene: KLHL41 were changed from Nemaline myopathy 9, 615731 (3) to Nemaline myopathy 9, 615731
Fetal anomalies v0.335 AUTS2 Rebecca Foulger edited their review of gene: AUTS2: Changed rating: RED
Inborn errors of metabolism v1.79 ISCU Sarah Leigh Added comment: Comment on mode of inheritance: PMID 29079705 reports a novel de novo dominant variant in ISCU associated with mitochondrial myopathy, which justifies the mode of inheritance recorded here.
Inborn errors of metabolism v1.79 ISCU Sarah Leigh Mode of inheritance for gene: ISCU was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mitochondrial disorders v1.477 ISCU Sarah Leigh Added comment: Comment on mode of inheritance: PMID 29079705 reports a novel de novo dominant variant in ISCU associated with mitochondrial myopathy, which justifies the mode of inheritance recorded here.
Mitochondrial disorders v1.477 ISCU Sarah Leigh Mode of inheritance for gene: ISCU was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.335 Rebecca Foulger List of related panels changed from to R21
Fetal anomalies v0.334 PKD1 Rebecca Foulger Mode of inheritance for gene: PKD1 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Fetal anomalies v0.333 SMARCAL1 Rebecca Foulger changed review comment from: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March and April 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Phenotype is not fetally-relevant. Action taken: Demoted SMARCAL1 gene rating from Green to Red.; to: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March and April 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: IUGR can present but is not severe. Action taken: Demoted SMARCAL1 gene rating from Green to Red.
Fetal anomalies v0.333 MFSD8 Rebecca Foulger commented on gene: MFSD8: Kept rating of MFSD8 as Red, following review of Neuronal ceroid lipofuscinosis genes by Richard Scott (Genomics England clinical team).
Fetal anomalies v0.333 VPS13B Rebecca Foulger changed review comment from: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: As RM notes: Cerebellar hypoplasia has definitely been reported as a possible feature (PMID:20683995) and that could be detectable prenatally: keep on the Fetal anomalies panel as a Green gene.; to: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: RM notes that Cerebellar hypoplasia has definitely been reported as a possible feature (PMID:20683995) and that could be detectable prenatally: keep on the Fetal anomalies panel as a Green gene.
Fetal anomalies v0.333 VPS13B Rebecca Foulger changed review comment from: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Cerebellar hypoplasia has definitely been reported as a possible feature (PMID:20683995) and that could be detectable prenatally: keep on the Fetal anomalies panel as a Green gene.; to: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: As RM notes: Cerebellar hypoplasia has definitely been reported as a possible feature (PMID:20683995) and that could be detectable prenatally: keep on the Fetal anomalies panel as a Green gene.
Fetal anomalies v0.333 VPS13B Rebecca Foulger Publications for gene: VPS13B were set to
Fetal anomalies v0.332 VPS13B Rebecca Foulger commented on gene: VPS13B: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Cerebellar hypoplasia has definitely been reported as a possible feature (PMID:20683995) and that could be detectable prenatally: keep on the Fetal anomalies panel as a Green gene.
Fetal anomalies v0.332 GALC Rebecca Foulger Classified gene: GALC as Green List (high evidence)
Fetal anomalies v0.332 GALC Rebecca Foulger Added comment: Comment on list classification: Promoted GALC from Red to Green based on review by Anna de Burca, and agreement from Rhiannon Mellis (GOSH) and Richard Scott (Genomics England Clinical team).
Fetal anomalies v0.332 GALC Rebecca Foulger Gene: galc has been classified as Green List (High Evidence).
Fetal anomalies v0.331 KCTD7 Rebecca Foulger commented on gene: KCTD7: Kept rating of KCTD7 as Red, following review of Neuronal ceroid lipofuscinosis genes by Richard Scott (Genomics England clinical team).
Fetal anomalies v0.331 CLN8 Rebecca Foulger commented on gene: CLN8: Kept rating of CLN8 as Red, following review of Neuronal ceroid lipofuscinosis genes by Richard Scott (Genomics England clinical team).
Fetal anomalies v0.331 CLN5 Rebecca Foulger commented on gene: CLN5: Kept rating of CLN5 as Red, following review of Neuronal ceroid lipofuscinosis genes by Richard Scott (Genomics England clinical team).
Fetal anomalies v0.331 CLN3 Rebecca Foulger commented on gene: CLN3: Kept rating of CLN3 as Red, following review of Neuronal ceroid lipofuscinosis genes by Richard Scott (Genomics England clinical team).
Fetal anomalies v0.331 TPP1 Rebecca Foulger commented on gene: TPP1: Kept rating of TPP1 as Red, following review of Neuronal ceroid lipofuscinosis genes by Richard Scott (Genomics England clinical team).
Fetal anomalies v0.331 PPT1 Rebecca Foulger commented on gene: PPT1: Kept rating of PPT1 as Red, following review of Neuronal ceroid lipofuscinosis genes by Richard Scott (Genomics England clinical team).
Fetal anomalies v0.331 CTSD Rebecca Foulger commented on gene: CTSD: Kept rating of CTSD as Green, following review of Neuronal ceroid lipofuscinosis genes by Richard Scott (Genomics England clinical team).
Fetal anomalies v0.331 PDHA1 Rebecca Foulger Phenotypes for gene: PDHA1 were changed from X-LINKED LEIGH SYNDROME; PYRUVATE DEHYDROGENASE E1-ALPHA DEFICIENCY IN FEMALES; INTELLECTUAL DISABILTIY to Pyruvate dehydrogenase E1-alpha deficiency; X-LINKED LEIGH SYNDROME; PYRUVATE DEHYDROGENASE E1-ALPHA DEFICIENCY IN FEMALES; INTELLECTUAL DISABILTIY
Fetal anomalies v0.330 PDHA1 Rebecca Foulger Publications for gene: PDHA1 were set to
Fetal anomalies v0.329 PDHA1 Rebecca Foulger commented on gene: PDHA1: Kept rating of PDHA1 as Green based on Green review by Anna de Burca, and agreement with Richard Scott from the Genomics England Clinical team.
Fetal anomalies v0.329 PTEN Rebecca Foulger changed review comment from: This gene was re-reviewed in a consistency check by Anna de Burca (Genomics England Clinical Team), and at a Fetal Working Group call on July 19th 2019 by Lyn Chitty, Anna de Burca, Richard Scott, Rhiannon Mellis, Rebecca Foulger and Ellen McDonagh. Outcome of review: No structural features. Demote from Green to Red. ; to: This gene was re-reviewed in a consistency check by Anna de Burca (Genomics England Clinical Team), and at a Fetal Working Group call on July 19th 2019 by Lyn Chitty, Anna de Burca, Richard Scott, Rhiannon Mellis, Rebecca Foulger and Ellen McDonagh. Outcome of review: Hydrocephalus is very unusual, and PTEN is on the Hydrocephalus panel because of the macrocephaly phenotype. Demote from Green to Red.
Intellectual disability v2.998 NFASC Sarah Leigh Classified gene: NFASC as Green List (high evidence)
Intellectual disability v2.998 NFASC Sarah Leigh Added comment: Comment on list classification: Associated with phenotype in OMIM and not in Gen2Phen. At least 3 variants identified in unrelated cases.
Intellectual disability v2.998 NFASC Sarah Leigh Gene: nfasc has been classified as Green List (High Evidence).
Intellectual disability v2.997 NFASC Sarah Leigh gene: NFASC was added
gene: NFASC was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: NFASC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NFASC were set to 28940097; 30124836; 30850329
Phenotypes for gene: NFASC were set to Neurodevelopmental disorder with central and peripheral motor dysfunction 618356
Review for gene: NFASC was set to GREEN
Added comment: Sources: Literature
Hereditary ataxia - adult onset v1.196 POLG2 Sarah Leigh Publications for gene: POLG2 were set to
Hereditary ataxia - adult onset v1.195 POLG2 Sarah Leigh Added comment: Comment on mode of inheritance: Reporting and characterization of a homozygous POLG2 variant in mitochondrial DNA depletion syndrome and in an autosomal recessive epilepsy family without ophthalmoplegia (PMID 27592148; 30157269; 31286721).
Hereditary ataxia - adult onset v1.195 POLG2 Sarah Leigh Mode of inheritance for gene: POLG2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathies - including childhood onset v1.34 POLG2 Sarah Leigh Publications for gene: POLG2 were set to 27604308
Molecular autopsy v0.99 POLG2 Sarah Leigh Publications for gene: POLG2 were set to 27604308
Molecular autopsy v0.98 POLG2 Sarah Leigh Added comment: Comment on mode of inheritance: Reporting and characterization of a homozygous POLG2 variant in mitochondrial DNA depletion syndrome and in an autosomal recessive epilepsy family without ophthalmoplegia (PMID 27592148; 30157269; 31286721).
Molecular autopsy v0.98 POLG2 Sarah Leigh Mode of inheritance for gene: POLG2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cardiomyopathies - including childhood onset v1.33 POLG2 Sarah Leigh Added comment: Comment on mode of inheritance: Reporting and characterization of a homozygous POLG2 variant in mitochondrial DNA depletion syndrome and in an autosomal recessive epilepsy family without ophthalmoplegia (PMID 27592148; 30157269; 31286721).
Cardiomyopathies - including childhood onset v1.33 POLG2 Sarah Leigh Mode of inheritance for gene: POLG2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Tumour predisposition - childhood onset v1.36 CTR9 Ivone Leong Phenotypes for gene: CTR9 were changed from Wilms tumour to Familial Wilms tumor
Tumour predisposition - childhood onset v1.35 CTR9 Ivone Leong Mode of inheritance for gene: CTR9 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Tumour predisposition - childhood onset v1.34 TRIM28 Ivone Leong Mode of inheritance for gene: TRIM28 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Tumour predisposition - childhood onset v1.33 TRIM28 Ivone Leong Phenotypes for gene: TRIM28 were changed from Wilms tumour to Familial Wilms tumor; Wilms tumour
Tumour predisposition - childhood onset v1.32 TRIM28 Shazia Mahamdallie reviewed gene: TRIM28: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29912901, 30694527, 30885698; Phenotypes: Familial Wilms tumor, Wilms tumor; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Tumour predisposition - childhood onset v1.32 CTR9 Shazia Mahamdallie reviewed gene: CTR9: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 25099282, 29292210; Phenotypes: Familial Wilms tumor; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Inherited bleeding disorders v1.156 IKZF5 Louise Daugherty Classified gene: IKZF5 as Green List (high evidence)
Inherited bleeding disorders v1.156 IKZF5 Louise Daugherty Added comment: Comment on list classification: New gene added. Appropriate phenotype, sufficient cases and external expert review (pers.comm) all support gene-disease association and relevance to this panel to rate gene to Green.
Inherited bleeding disorders v1.156 IKZF5 Louise Daugherty Gene: ikzf5 has been classified as Green List (High Evidence).
Inherited bleeding disorders v1.155 IKZF5 Louise Daugherty gene: IKZF5 was added
gene: IKZF5 was added to Inherited bleeding disorders. Sources: Literature
Mode of inheritance for gene: IKZF5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: IKZF5 were set to 31217188
Phenotypes for gene: IKZF5 were set to Thrombocytopenia
Review for gene: IKZF5 was set to GREEN
Added comment: From abstract Lentaigne C et al (2019) PMID: 31217188: To identify novel causes of hereditary thrombocytopenia, we performed a genetic association analysis of whole-genome sequencing (WGS) data from 13,037 individuals enrolled in the NIHR BioResource, including 233 cases with isolated thrombocytopenia. We found an association between rare variants in the transcription factor (TF)-encoding gene IKZF5 and thrombocytopenia. We report five causal missense variants in or near IKZF5 zinc fingers (Znfs), of which two occurred de novo and three co-segregated in three pedigrees. A canonical DNA-Znf binding model predicts that three of the variants alter DNA recognition. Expression studies showed that chromatin binding was disrupted in mutant compared to wild-type (WT) IKZF5 and electron microscopy (EM) revealed a reduced quantity of alpha granules in normally sized platelets. Proplatelet formation (PPF) was reduced in megakaryocytes (MKs) from seven cases relative to six controls. Comparison of RNA-seq data from platelets, monocytes, neutrophils and CD4+ T-cells from three cases and 14 healthy controls showed 1,194 differentially expressed genes (DEGs) in platelets but only four DEGs in each of the other blood cell types. In conclusion, IKZF5 is a novel transcriptional regulator of megakaryopoiesis and the eighth transcription factor associated with dominant thrombocytopenia in humans.
Sources: Literature
Tumour predisposition - childhood onset v1.32 TRIM28 Ivone Leong reviewed gene: TRIM28: Rating: GREEN; Mode of pathogenicity: ; Publications: 29912901, 30694527, 30885698 ; Phenotypes: ; Mode of inheritance:
Tumour predisposition - childhood onset v1.32 CTR9 Ivone Leong reviewed gene: CTR9: Rating: GREEN; Mode of pathogenicity: ; Publications: 25099282, 29292210; Phenotypes: ; Mode of inheritance:
Tumour predisposition - childhood onset v1.31 TRIM28 Ivone Leong gene: TRIM28 was added
gene: TRIM28 was added to Tumour predisposition - childhood onset. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: TRIM28 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TRIM28 were set to 29912901; 30694527; 30885698
Phenotypes for gene: TRIM28 were set to Wilms tumour
Tumour predisposition - childhood onset v1.31 CTR9 Ivone Leong gene: CTR9 was added
gene: CTR9 was added to Tumour predisposition - childhood onset. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: CTR9 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CTR9 were set to 25099282; 29292210
Phenotypes for gene: CTR9 were set to Wilms tumour
Undiagnosed metabolic disorders v1.131 TANGO2 Sarah Leigh Classified gene: TANGO2 as Green List (high evidence)
Undiagnosed metabolic disorders v1.131 TANGO2 Sarah Leigh Added comment: Comment on list classification: Based on recommendations of Helen Britain (Clinical Fellow, Genomics England) as cases will have of periods of decompensation that are associated with hypoglycaemia and hyperammonaemia.
Undiagnosed metabolic disorders v1.131 TANGO2 Sarah Leigh Gene: tango2 has been classified as Green List (High Evidence).
Undiagnosed metabolic disorders v1.130 TANGO2 Sarah Leigh gene: TANGO2 was added
gene: TANGO2 was added to Undiagnosed metabolic disorders. Sources: Other
Mode of inheritance for gene: TANGO2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TANGO2 were set to Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration 616878
Review for gene: TANGO2 was set to GREEN
Added comment: Sources: Other
Undiagnosed metabolic disorders v1.129 STAT2 Sarah Leigh Classified gene: STAT2 as Amber List (moderate evidence)
Undiagnosed metabolic disorders v1.129 STAT2 Sarah Leigh Added comment: Comment on list classification: Based on recommendation of Helen Britain (Clinical Fellow, Genomics England), that the majority of cases will be presenting in the context of overwhelming infection. The raised lactate and encephalomyopathy are potentially relevant phenotypes for this panel, however more evidence is needed on how common this presentation is, and whether it is always clearly associated with a proven infection.
Undiagnosed metabolic disorders v1.129 STAT2 Sarah Leigh Gene: stat2 has been classified as Amber List (Moderate Evidence).
Undiagnosed metabolic disorders v1.128 STAT2 Sarah Leigh gene: STAT2 was added
gene: STAT2 was added to Undiagnosed metabolic disorders. Sources: Other
Mode of inheritance for gene: STAT2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: STAT2 were set to Immunodeficiency 44 616636
Review for gene: STAT2 was set to AMBER
Added comment: Sources: Other
Undiagnosed metabolic disorders v1.127 IER3IP1 Sarah Leigh Classified gene: IER3IP1 as Amber List (moderate evidence)
Undiagnosed metabolic disorders v1.127 IER3IP1 Sarah Leigh Added comment: Comment on list classification: Based on recommendation of Helen Britain (Clinical Fellow, Genomics England), that patients will present with features of microcephaly / neonatal diabetes / developmental delay, rather than metabolic disorder.
Undiagnosed metabolic disorders v1.127 IER3IP1 Sarah Leigh Gene: ier3ip1 has been classified as Amber List (Moderate Evidence).
Undiagnosed metabolic disorders v1.126 IER3IP1 Sarah Leigh gene: IER3IP1 was added
gene: IER3IP1 was added to Undiagnosed metabolic disorders. Sources: Other
Mode of inheritance for gene: IER3IP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IER3IP1 were set to 21835305; 22991235; 24138066
Phenotypes for gene: IER3IP1 were set to Microcephaly, epilepsy, and diabetes syndrome 614231
Review for gene: IER3IP1 was set to AMBER
Added comment: Sources: Other
Mitochondrial disorders v1.476 POLG2 Sarah Leigh changed review comment from: Comment on mode of inheritance: Reporting and characterization of a homozygous POLG2 variant in mitochondrial DNA depletion syndrome (PMID 27592148; 30157269); to: Comment on mode of inheritance: Reporting and characterization of a homozygous POLG2 variant in mitochondrial DNA depletion syndrome and in an autosomal recessive epilepsy family without ophthalmoplegia (PMID 27592148; 30157269; 31286721).
Inborn errors of metabolism v1.78 POLG2 Sarah Leigh Added comment: Comment on mode of inheritance: Reporting and characterization of a homozygous POLG2 variant in mitochondrial DNA depletion syndrome and in an autosomal recessive epilepsy family without ophthalmoplegia (PMID 27592148; 30157269; 31286721).
Inborn errors of metabolism v1.78 POLG2 Sarah Leigh Mode of inheritance for gene: POLG2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Inborn errors of metabolism v1.78 POLG2 Sarah Leigh Added comment: Comment on mode of inheritance: Reporting and characterization of a homozygous POLG2 variant in mitochondrial DNA depletion syndrome and in an autosomal recessive epilepsy family without ophthalmoplegia (PMID 27592148; 30157269; 31286721).
Inborn errors of metabolism v1.78 POLG2 Sarah Leigh Mode of inheritance for gene: POLG2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Limb disorders v1.56 SOX9 Eleanor Williams commented on gene: SOX9: Associated with Campomelic dysplasia (114290) in OMIM and CAMPOMELIC DYSPLASIA and PIERRE ROBIN SEQUENCE in Gene2Phenotype (both confirmed).

Publications relating to the duplications in the region between KCNJ2 and SOX9:

PMID: 19639023 - Kurth et al 2009 - investigated four families with symmetric brachydactyly of the hands and feet as well as hyponychia or anonychia. All affected were of normal height and had no other skeletal abnormality. They identified overlapping duplications in a ∼2 Mb interval on chromosome 17q24.3. Comparison of the four duplications revealed a minimal critical region of ∼1.2 Mb encompassing a large gene desert between KCNJ2 and SOX9. In situ hybridizations in mouse embryos, showed that Sox9 was strongly expressed in the distal mesenchymal condensations at embryonic day (E) 12.5 that will later develop into the terminal phalanges and, at a later time point (E17.5), in the anlagen of the developing claw.

PMID: 27706140 - Franke et al 2016 - used chromosome conformation capture methods to look at topologically associated domains in patient cells and mouse models where the regulatory region next to SOX9 is duplicated. They generated mice with a duplicated region associated with Cooks syndrome as reported by Kurth et al 2009 (which they call Dup-C). cHi-C of E12.5 Dup-C limb buds showed a new chromatin domain corresponding to the duplicated region.
RNA sequencing expression analysis of Dup-C limb buds at E12.5 and E17.5 confirmed the upregulation of Kcnj2, whereas other genes around the locus stayed unchanged, in particular Sox9, but also Kcnj16. Thus, the inclusion of Kcnj2 in the neo-TAD resulted in its activation by regulatory elements that originally belonged to the Sox9 TAD.


Other publications.
PMID: 21373255 - Corbani et al 2011 - reported patient with SOX9 missense mutation and mild form of campomelic dysplasia. Features include short stature, dysmorphic facial features, limitation of supination and pronation of the forearms, dysplastic nails, and bone abnormalities consisting especially of cone-shaped epiphyses of the middle phalanx of the 2nd fingers, brachydactyly and clinodactyly of the middle phalanx of both 5th fingers, short 4th metacarpals, radial and femoral head subluxation, hypoplastic scapulae, humeral and ulnar epiphyseal abnormalities, unossified symphysis pubis, and a significant delay in bone age.

PMID: 24704791 - Takenouchi et al 2014 - report patient with many features of the type 2 collagen disorder including micrognathia, cleft palate, flat midface, and visual and hearing impairment, and a retarded enchondral ossification of the appendicular skeleton during the infantile period. The patient had in addition severe developmental delay. A de novo heterozygous missense mutation, c.239T>G p.Val80Gly, in exon 1 of SOX9 was found.

Summary:
Evidence that duplication of a region upstream of SOX9 can result in a brachydactyly phenotype. This appears to be as a result of increased expression of KCNJ2. It maybe most appropriate to add this upstream region as a CNV.
Fetal anomalies v0.329 SLC4A4 Rebecca Foulger Publications for gene: SLC4A4 were set to
Fetal anomalies v0.328 SLC4A4 Rebecca Foulger commented on gene: SLC4A4: SLC4A4 was re-reviewed by Anna de Burca (Genomics England clinical team) to determine if patients presented with cataracts. Anna notes that there aren’t very many published cases and not all had cataracts. Of those that did, PMID:16636648 cataracts were definitely not congenital and in PMID:11131345 they were only picked up at 4 years so probably not congenital either. Therefore appropriate to remain Red.
Fetal anomalies v0.328 VDR Rebecca Foulger Classified gene: VDR as Amber List (moderate evidence)
Fetal anomalies v0.328 VDR Rebecca Foulger Added comment: Comment on list classification: Demoted rating from Green to Amber following discussions with Anna de Burca (Genomics England Clinical Team) and Rhiannon Mellis (Great Ormond Street). As Anna and Rhiannon note: rickets due to VDR could theoretically present in a fetus of a homozygous mother, as Melita suggested, but it would actually be caused by the mother’s vitamin D status irrespective of the baby’s genotype. Therefore, rather than performing a fetal exome, it would be better investigating the mother, who would have clinical signs and biochemical abnormalities in her own right.
Fetal anomalies v0.328 VDR Rebecca Foulger Gene: vdr has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.327 VDR Rebecca Foulger changed review comment from: This gene was reviewed by Anna de Burca (Genomics England clinical team) and Melita Irving. Melita reports that difficult to determine if skeletal features present antenatally as often mother has vitamin D deficiency too, so on balance probably should be Green.; to: This gene was reviewed by Anna de Burca (Genomics England clinical team) and Melita Irving. Melita reports that difficult to determine if skeletal features present antenatally as often mother has vitamin D deficiency too.
Undiagnosed metabolic disorders v1.125 POLG2 Sarah Leigh Publications for gene: POLG2 were set to 27604308
Undiagnosed metabolic disorders v1.124 POLG2 Sarah Leigh Added comment: Comment on mode of inheritance: Reporting and characterization of a homozygous POLG2 variant in mitochondrial DNA depletion syndrome and in an autosomal recessive epilepsy family without ophthalmoplegia (PMID 27592148; 30157269; 31286721).
Undiagnosed metabolic disorders v1.124 POLG2 Sarah Leigh Mode of inheritance for gene: POLG2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Inherited white matter disorders v1.71 POLG2 Sarah Leigh Publications for gene: POLG2 were set to 25655951
Inherited white matter disorders v1.70 POLG2 Sarah Leigh Added comment: Comment on mode of inheritance: Reporting and characterization of a homozygous POLG2 variant in mitochondrial DNA depletion syndrome and in an autosomal recessive epilepsy family without ophthalmoplegia (PMID 27592148; 30157269; 31286721).
Inherited white matter disorders v1.70 POLG2 Sarah Leigh Mode of inheritance for gene: POLG2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.9 POLG2 Sarah Leigh Publications for gene: POLG2 were set to
White matter disorders and cerebral calcification - narrow panel v1.8 POLG2 Sarah Leigh Added comment: Comment on mode of inheritance: Reporting and characterization of a homozygous POLG2 variant in mitochondrial DNA depletion syndrome and in an autosomal recessive epilepsy family without ophthalmoplegia (PMID 27592148; 30157269; 31286721).
White matter disorders and cerebral calcification - narrow panel v1.8 POLG2 Sarah Leigh Mode of inheritance for gene: POLG2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Neuromuscular disorders v1.6 POLG2 Sarah Leigh Publications for gene: POLG2 were set to 25929793
Neuromuscular disorders v1.5 POLG2 Sarah Leigh Added comment: Comment on mode of inheritance: Reporting and characterization of a homozygous POLG2 variant in mitochondrial DNA depletion syndrome and in an autosomal recessive epilepsy family without ophthalmoplegia (PMID 27592148; 30157269; 31286721).
Neuromuscular disorders v1.5 POLG2 Sarah Leigh Mode of inheritance for gene: POLG2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rhabdomyolysis and metabolic muscle disorders v1.28 POLG2 Sarah Leigh Publications for gene: POLG2 were set to 25929793
Rhabdomyolysis and metabolic muscle disorders v1.27 POLG2 Sarah Leigh Added comment: Comment on mode of inheritance: Reporting and characterization of a homozygous POLG2 variant in mitochondrial DNA depletion syndrome (PMID 27592148; 30157269)
Rhabdomyolysis and metabolic muscle disorders v1.27 POLG2 Sarah Leigh Mode of inheritance for gene: POLG2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mitochondrial disorders v1.476 POLG2 Sarah Leigh Publications for gene: POLG2 were set to 27592148; 30157269; 21555342
Genetic epilepsy syndromes v1.198 POLG2 Sarah Leigh Classified gene: POLG2 as Amber List (moderate evidence)
Genetic epilepsy syndromes v1.198 POLG2 Sarah Leigh Added comment: Comment on list classification: Single case of recessive epilepsy.
Genetic epilepsy syndromes v1.198 POLG2 Sarah Leigh Gene: polg2 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v1.197 POLG2 Sarah Leigh gene: POLG2 was added
gene: POLG2 was added to Genetic epilepsy syndromes. Sources: Literature
Mode of inheritance for gene: POLG2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLG2 were set to 31286721; 27592148; 30157269
Phenotypes for gene: POLG2 were set to Autosomal Recessive Epilepsy Family Without Ophthalmoplegia
Review for gene: POLG2 was set to AMBER
Added comment: Single case of Autosomal Recessive Epilepsy Family Without Ophthalmoplegia in a 27-year-old Pakistani male, who was homozygous for POLG2 c.694G>A, p.G232S. Both his parents were heterozygous for this variant, and none of them had liver disease, ophthalmoplegia, ptosis, nystagmus, or myopathy, and the parents showed no symptoms of epilepsy or ophthalmoplegia.
Sources: Literature
Intellectual disability v2.996 POLR2A Konstantinos Varvagiannis gene: POLR2A was added
gene: POLR2A was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: POLR2A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: POLR2A were set to 31353023
Phenotypes for gene: POLR2A were set to Generalized hypotonia; Global developmental delay; Feeding difficulties
Penetrance for gene: POLR2A were set to unknown
Review for gene: POLR2A was set to GREEN
gene: POLR2A was marked as current diagnostic
Added comment: Haijes et al. (2019 - PMID: 31353023) report on 16 individuals with heterozygous de novo POLR2A variants.

DD in all domains was observed in all individuals, ranging from mild to severe (in 8/16 moderate or more severe). The developmental scores were stable over time (as for eventual catch-up/decline) supporting relevance to the current panel.

POLR2A encodes RPB1, the largest subunit of RNA polymerase II (pol II). Pol II is responsible for the transcription of all protein coding genes as well as several long/short non-coding RNA genes.

Missense, in-frame deletions as well as truncating mutations were observed. POLR2A has a pLI of 1 and a Z-score for missense variants of 7.13 (one of the highest ones). The reported variants did not cluster in specific domains of the protein although many were in regions relatively depleted in benign variants in gnomAD (stretches of desert Z-scores). Measures such as the CADD scores did not discriminate between deleterious ones and those in gnomAD.

Different layers of structural analyses, functional analyses (impaired growth in S. cerevisiae in genetic background lacking transcr. factors Dst1 / Sub1 - suggesting reduced transcriptional fidelity / reduced HeLa cell viability) or phenotypic overlap were used to classify variants in probably disease causing (11), possibly disease causing (4 - only based on phenotypic overlap) or of unknown effect (1 variant - due to unavailable/incomplete phenotype).

Some variants were predicted to act by haploinsufficiency while others (missense ones) by a dominant-negative mechanism, the latter being more likely to result in severe phenotypes.

Mutations in genes encoding subunits of pol III (responsible for tRNA synthesis) are associated with leukodystrophy phenotypes with some limited overlap with POLR2A (delayed myelination/white-matter loss/tooth misalignment). Mutations in genes encoding other subunits of pol II (other than RPB1 encoded by POLR2A) have not been implicated in disease though.

POLR2A is not associated with any phenotype in OMIM/G2P. This gene is included in panels for ID offered by some diagnostic laboratories [eg. Utrecht UMC - affiliation of many co-authors of this study or GeneDx].

As a result, this gene can be considered for inclusion in the ID panel probably as green, or amber.
Sources: Literature
Intellectual disability v2.996 AFF3 Konstantinos Varvagiannis changed review comment from: Voisin et al. (2019 - https://doi.org/10.1101/693937) report on 10 individuals with de novo missense AFF3 variants affecting a 9-amino-acid sequence (degron) important for the protein's degradation and summarize the phenotype of an additional individual previously described by Steichen-Gersdorf et al. (2008 - PMID: 18616733) with a 500 kb affecting only AFF3 (LAF4) and removing also this sequence.

The phenotype of missense variants consisted of kidney anomalies, mesomelic dysplasia, seizures, hypertrichosis, intellectual disability and pulmonary problems and was overlapping with that of the deletion. [10 of 11 subjects exhibited severe developmental epileptic encephalopathy].

9 probands harbored missense variants affecting the codon 258 while one individual had a variant affecting codon 260 [c.772G>T or p.Ala258Ser (x2), c.772G>A or p.Ala258Thr (x6), c.773C>T or p.Ala258Val (x1) and c.779T>G or p.(Val260Gly) (x1) - NM_001025108.1 / NP_001020279.1]. The deletion removed exons 4-13.

AFF1-4 are ALF transcription factor paralogs, components of the transcriptional super elongation complex regulating expression of genes involved in neurogenesis and development.

Using HEK293T cells expressing FLAG-tagged AFF3 (and AFF4) wt or mutants, accumulation of mutated forms was shown upon immunoblot.

Aff3+/- and/or -/- mice exhibit skeletal defects. These were more pronounced in homozygous mice which demonstrated also some elements in favor of kidney dysfunction and/or metabolic deregulation and possible neurological dysfunction (signs of impaired hearing and diminished grip strength). Homozygous mice had CNS anomalies (enlarged lateral ventricles and decreased corpus callosum size) similar to some affected individuals, although these were not observed in another Aff3-/- model. Knock-in mice modeling the microdeletion and the Ala258Thr variant displayed lower mesomelic limb deformities and early lethality respectively [cited PMIDs : 21677750, 25660031, knock-in model was part of the present study].

Accumulation of the protein in zebrafish (by overexpression of the human wt AFF3 mRNA), led to morphological defects.

Reanalysis of transcriptome data from previously generated HEK293T cell lines knocked down for AFF2, AFF3 and AFF4 by shRNAs (study) suggested that these transcription factors are not redundant.

Finally, CHOPS syndrome (#616368) due to mutations of AFF4 also leading to increased protein stability presents a partially overlapping phenotype (incl. cognitive impairment) to that of AFF3.
----
In G2P, AFF3 is associated with Skeletal dysplasia with severe neurological disease (disease confidence : probable / ID and seizures among the assigned phenotypes). There is no associated phenotype in OMIM.
Some diagnostic laboratories include AFF3 in their ID panel (eg. among the many co-authors' affiliations GeneDx and Victorian Clinical Genetics - which was already listed as source for AFF3 in the current panel).
----
As a result this gene can be considered for upgrade to green (relevant phenotype and severity, sufficient cases, evidence for accumulation similar to AFF4, animal models, etc) or amber (pending publication of the article).; to: Voisin et al. (2019 - https://doi.org/10.1101/693937) report on 10 individuals with de novo missense AFF3 variants affecting a 9-amino-acid sequence (degron) important for the protein's degradation and summarize the phenotype of an additional individual previously described by Steichen-Gersdorf et al. (2008 - PMID: 18616733) with a 500 kb affecting only AFF3 (LAF4) and removing also this sequence.

The phenotype of missense variants consisted of kidney anomalies, mesomelic dysplasia, seizures, hypertrichosis, intellectual disability and pulmonary problems and was overlapping with that of the deletion. [10 of 11 subjects exhibited severe developmental epileptic encephalopathy].

9 probands harbored missense variants affecting the codon 258 while one individual had a variant affecting codon 260 [c.772G>T or p.Ala258Ser (x2), c.772G>A or p.Ala258Thr (x6), c.773C>T or p.Ala258Val (x1) and c.779T>G or p.(Val260Gly) (x1) - NM_001025108.1 / NP_001020279.1]. The deletion removed exons 4-13.

AFF1-4 are ALF transcription factor paralogs, components of the transcriptional super elongation complex regulating expression of genes involved in neurogenesis and development.

Using HEK293T cells expressing FLAG-tagged AFF3 (and AFF4) wt or mutants, accumulation of mutated forms was shown upon immunoblot.

Aff3+/- and/or -/- mice exhibit skeletal defects. These were more pronounced in homozygous mice which demonstrated also some elements in favor of kidney dysfunction and/or metabolic deregulation and possible neurological dysfunction (signs of impaired hearing and diminished grip strength). Homozygous mice had CNS anomalies (enlarged lateral ventricles and decreased corpus callosum size) similar to some affected individuals, although these were not observed in another Aff3-/- model. Knock-in mice modeling the microdeletion and the Ala258Thr variant displayed lower mesomelic limb deformities and early lethality respectively [cited PMIDs : 21677750, 25660031, knock-in model was part of the present study].

Accumulation of the protein in zebrafish (by overexpression of the human wt AFF3 mRNA), led to morphological defects.

Reanalysis of transcriptome data from previously generated HEK293T cell lines knocked down for AFF2, AFF3 and AFF4 by shRNAs (study) suggested that these transcription factors are not redundant.

Finally, CHOPS syndrome (#616368) due to mutations of AFF4 also leading to increased protein stability presents a partially overlapping phenotype (incl. cognitive impairment) to that of AFF3.
----
Shimizu et al. (8/2019 - PMID: 31388108) describe an additional individual with de novo AFF3 missense variant. The phenotype overlaps with that summarized by Voisin et al. incl. mesomelic dysplasia with additional skeletal anomalies, bilateral kidney hypoplasia and severe DD at the age of 2.5 years. Seizures and pulmonary problems were not observed. Although a different RefSeq is used the variant is among those also reported by Voisin et al. [NM_002285.2:c.697G>A (p.Ala233Thr) corresponding to NM_001025108.1:c.772G>A (p.Ala258Thr)].
----
In G2P, AFF3 is associated with Skeletal dysplasia with severe neurological disease (disease confidence : probable / ID and seizures among the assigned phenotypes). There is no associated phenotype in OMIM.
Some diagnostic laboratories include AFF3 in their ID panel (eg. among the many co-authors' affiliations GeneDx and Victorian Clinical Genetics - which was already listed as source for AFF3 in the current panel).
----
As a result this gene can be considered for upgrade to green (relevant phenotype and severity, sufficient cases, evidence for accumulation similar to AFF4, animal models, etc) or amber (pending publication of the article).

[Review modified to add additional reference/case report]
Genetic epilepsy syndromes v1.196 AFF3 Konstantinos Varvagiannis changed review comment from: Voisin et al. (2019 - https://doi.org/10.1101/693937) report on 10 individuals with de novo missense AFF3 variants affecting a 9-amino-acid sequence (degron) important for the protein's degradation and summarize the phenotype of an additional individual previously described by Steichen-Gersdorf et al. (2008 - PMID: 18616733) with a 500 kb affecting only AFF3 (LAF4) and removing also this sequence.

The phenotype of missense variants consisted of kidney anomalies, mesomelic dysplasia, seizures, hypertrichosis, intellectual disability and pulmonary problems and was overlapping with that of the deletion. [10 of 11 subjects exhibited severe developmental epileptic encephalopathy].

9 probands harbored missense variants affecting the codon 258 while one individual had a variant affecting codon 260 [c.772G>T or p.Ala258Ser (x2), c.772G>A or p.Ala258Thr (x6), c.773C>T or p.Ala258Val (x1) and c.779T>G or p.(Val260Gly) (x1) - NM_001025108.1 / NP_001020279.1]. The deletion removed exons 4-13.

AFF1-4 are ALF transcription factor paralogs, components of the transcriptional super elongation complex regulating expression of genes involved in neurogenesis and development.

Using HEK293T cells expressing FLAG-tagged AFF3 (and AFF4) wt or mutants, accumulation of mutated forms was shown upon immunoblot.

Aff3+/- and/or -/- mice exhibit skeletal defects. These were more pronounced in homozygous mice which demonstrated also some elements in favor of kidney dysfunction and/or metabolic deregulation and possible neurological dysfunction (signs of impaired hearing and diminished grip strength). Homozygous mice had CNS anomalies (enlarged lateral ventricles and decreased corpus callosum size) similar to some affected individuals, although these were not observed in another Aff3-/- model. Knock-in mice modeling the microdeletion and the Ala258Thr variant displayed lower mesomelic limb deformities and early lethality respectively [cited PMIDs : 21677750, 25660031, knock-in model was part of the present study].

Accumulation of the protein in zebrafish (by overexpression of the human wt AFF3 mRNA), led to morphological defects.

Reanalysis of transcriptome data from previously generated HEK293T cell lines knocked down for AFF2, AFF3 and AFF4 by shRNAs (study) suggested that these transcription factors are not redundant.

Finally, CHOPS syndrome (#616368) due to mutations of AFF4 also leading to increased protein stability presents a partially overlapping phenotype (incl. cognitive impairment) to that of AFF3.
----
In G2P, AFF3 is associated with Skeletal dysplasia with severe neurological disease (disease confidence : probable / ID and seizures among the assigned phenotypes). There is no associated phenotype in OMIM.
----
As a result this gene can be considered for inclusion in the epilepsy panel as green (relevant phenotype and severity, sufficient cases, evidence for accumulation similar to AFF4, animal models, etc) or amber (pending publication of the article).
Sources: Literature; to: Voisin et al. (2019 - https://doi.org/10.1101/693937) report on 10 individuals with de novo missense AFF3 variants affecting a 9-amino-acid sequence (degron) important for the protein's degradation and summarize the phenotype of an additional individual previously described by Steichen-Gersdorf et al. (2008 - PMID: 18616733) with a 500 kb affecting only AFF3 (LAF4) and removing also this sequence.

The phenotype of missense variants consisted of kidney anomalies, mesomelic dysplasia, seizures, hypertrichosis, intellectual disability and pulmonary problems and was overlapping with that of the deletion. [10 of 11 subjects exhibited severe developmental epileptic encephalopathy].

9 probands harbored missense variants affecting the codon 258 while one individual had a variant affecting codon 260 [c.772G>T or p.Ala258Ser (x2), c.772G>A or p.Ala258Thr (x6), c.773C>T or p.Ala258Val (x1) and c.779T>G or p.(Val260Gly) (x1) - NM_001025108.1 / NP_001020279.1]. The deletion removed exons 4-13.

AFF1-4 are ALF transcription factor paralogs, components of the transcriptional super elongation complex regulating expression of genes involved in neurogenesis and development.

Using HEK293T cells expressing FLAG-tagged AFF3 (and AFF4) wt or mutants, accumulation of mutated forms was shown upon immunoblot.

Aff3+/- and/or -/- mice exhibit skeletal defects. These were more pronounced in homozygous mice which demonstrated also some elements in favor of kidney dysfunction and/or metabolic deregulation and possible neurological dysfunction (signs of impaired hearing and diminished grip strength). Homozygous mice had CNS anomalies (enlarged lateral ventricles and decreased corpus callosum size) similar to some affected individuals, although these were not observed in another Aff3-/- model. Knock-in mice modeling the microdeletion and the Ala258Thr variant displayed lower mesomelic limb deformities and early lethality respectively [cited PMIDs : 21677750, 25660031, knock-in model was part of the present study].

Accumulation of the protein in zebrafish (by overexpression of the human wt AFF3 mRNA), led to morphological defects.

Reanalysis of transcriptome data from previously generated HEK293T cell lines knocked down for AFF2, AFF3 and AFF4 by shRNAs (study) suggested that these transcription factors are not redundant.

Finally, CHOPS syndrome (#616368) due to mutations of AFF4 also leading to increased protein stability presents a partially overlapping phenotype (incl. cognitive impairment) to that of AFF3.
----
In G2P, AFF3 is associated with Skeletal dysplasia with severe neurological disease (disease confidence : probable / ID and seizures among the assigned phenotypes). There is no associated phenotype in OMIM.
----
As a result this gene can be considered for inclusion in the epilepsy panel as green (relevant phenotype and severity, sufficient cases, evidence for accumulation similar to AFF4, animal models, etc) or amber (pending publication of the article).
Sources: Literature

---------------

Shimizu et al. (8/2019 - PMID: 31388108) describe an additional individual with de novo AFF3 missense variant. The phenotype overlaps with that summarized by Voisin et al. incl. mesomelic dysplasia with additional skeletal anomalies, bilateral kidney hypoplasia and severe DD at the age of 2.5 years. Seizures and pulmonary problems were not observed. Although a different RefSeq is used the variant is among those also reported by Voisin et al. [NM_002285.2:c.697G>A (p.Ala233Thr) corresponding to NM_001025108.1:c.772G>A (p.Ala258Thr)].
Limb disorders v1.56 SMAD6 Eleanor Williams commented on gene: SMAD6: Added Incomplete penetrance as Yang et al 2019 found only 20% penetrance for LOF variant carriers.
Limb disorders v1.56 SMAD6 Eleanor Williams Penetrance for gene SMAD6 was set from to None
Congenital myopathy v1.156 TRIP4 Ivone Leong Phenotypes for gene: TRIP4 were changed from severe congenital myopathy with congenital bone fractures, 616866 to severe congenital myopathy with congenital bone fractures, 616866; Spinal muscular atrophy with congenital bone fractures 1, 616866
Congenital myopathy v1.155 SRPK3 Ivone Leong reviewed gene: SRPK3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Congenital myopathy v1.155 KLHL9 Ivone Leong Phenotypes for gene: KLHL9 were changed from Early onset distal myopathy to Early onset distal myopathy; Nemaline myopathy
Limb disorders v1.55 SMAD6 Eleanor Williams Publications for gene: SMAD6 were set to
Limb disorders v1.54 SMAD6 Eleanor Williams Phenotypes for gene: SMAD6 were changed from radioulnar synostosis to radioulnar synostosis
Limb disorders v1.54 SMAD6 Eleanor Williams Phenotypes for gene: SMAD6 were changed from to radioulnar synostosis
Limb disorders v1.53 SMAD6 Eleanor Williams changed review comment from: Not associated with radioulnar synostosis in OMIM or Gene2Phenotype, although is associated with susceptibility to craniosynostosis and Aortic valve disease 2.

PMID: 31138930 - Yang et al 2019 - investigated 140 sporadic patients and 11 families with RUS of an unknown cause. Potentially disease causing variants were found in SMAD6 in 30 individuals from 27 families. In 22 individuals the variants were detected by whole exome sequencing and confirmed by Sanger sequencing. In the remaining 8 individuals targetting sequencing of SMAD6 using Sanger sequencing was performed. 27 different variants were identified (19 LOF and 8 missense), in 24 sporadic patients and three families. Parental genomic DNA was available for 11 probands with SMAD6 rare variants. Sanger sequencing validated that four variants were de novo, six were inherited from the probands’ unaffected mother, and one was inherited from the probands’ unaffected father.
Reduced penetrance was found - after excluding the index cases, the found 2/10 SMAD6- LOF carriers have nsRUS. Therefore, the penetrance of RUS in SMAD6-LOF cases is reduced (~20%).
No significant associations were observed between BMP2-Chr20–7106289T-C genotype and nsRUS in cases with SMAD6 rare variants.; to: Not associated with radioulnar synostosis in OMIM or Gene2Phenotype, although is associated with susceptibility to craniosynostosis and Aortic valve disease 2.

PMID: 31138930 - Yang et al 2019 - investigated 140 sporadic patients and 11 families with Radioulnar synostosis (RUS) of an unknown cause. Potentially disease causing variants were found in SMAD6 in 30 individuals from 27 families. In 22 individuals the variants were detected by whole exome sequencing and confirmed by Sanger sequencing. In the remaining 8 individuals targeted Sanger sequencing of SMAD6 was performed. 27 different variants were identified (19 LOF and 8 missense), in 24 sporadic patients and three families. Parental genomic DNA was available for 11 probands with SMAD6 rare variants. Sanger sequencing validated that four variants were de novo, six were inherited from the probands’ unaffected mother, and one was inherited from the probands’ unaffected father.
Reduced penetrance was found - after excluding the index cases, the found 2/10 SMAD6- LOF carriers have nsRUS. Therefore, the penetrance of RUS in SMAD6-LOF cases is reduced (~20%).
No significant associations were observed between BMP2-Chr20–7106289T-C genotype and nsRUS in cases with SMAD6 rare variants.
Limb disorders v1.53 SMAD6 Eleanor Williams commented on gene: SMAD6: Not associated with radioulnar synostosis in OMIM or Gene2Phenotype, although is associated with susceptibility to craniosynostosis and Aortic valve disease 2.

PMID: 31138930 - Yang et al 2019 - investigated 140 sporadic patients and 11 families with RUS of an unknown cause. Potentially disease causing variants were found in SMAD6 in 30 individuals from 27 families. In 22 individuals the variants were detected by whole exome sequencing and confirmed by Sanger sequencing. In the remaining 8 individuals targetting sequencing of SMAD6 using Sanger sequencing was performed. 27 different variants were identified (19 LOF and 8 missense), in 24 sporadic patients and three families. Parental genomic DNA was available for 11 probands with SMAD6 rare variants. Sanger sequencing validated that four variants were de novo, six were inherited from the probands’ unaffected mother, and one was inherited from the probands’ unaffected father.
Reduced penetrance was found - after excluding the index cases, the found 2/10 SMAD6- LOF carriers have nsRUS. Therefore, the penetrance of RUS in SMAD6-LOF cases is reduced (~20%).
No significant associations were observed between BMP2-Chr20–7106289T-C genotype and nsRUS in cases with SMAD6 rare variants.
Congenital myopathy v1.154 KLHL9 Ivone Leong reviewed gene: KLHL9: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Congenital myopathy v1.154 KLHL9 Ivone Leong Phenotypes for gene: KLHL9 were changed from Nemaline myopathy; early onset distal myopathy to Early onset distal myopathy
Congenital myopathy v1.153 KLHL9 Ivone Leong Phenotypes for gene: KLHL9 were changed from Nemaline myopathy to Nemaline myopathy; early onset distal myopathy
Genetic epilepsy syndromes v1.196 AFF3 Rebecca Foulger Tag missense tag was added to gene: AFF3.
Tag watchlist tag was added to gene: AFF3.
Genetic epilepsy syndromes v1.196 AFF3 Rebecca Foulger Classified gene: AFF3 as Amber List (moderate evidence)
Genetic epilepsy syndromes v1.196 AFF3 Rebecca Foulger Gene: aff3 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v1.195 AFF3 Rebecca Foulger commented on gene: AFF3
Genetic epilepsy syndromes v1.195 WWOX Rebecca Foulger commented on gene: WWOX: Usha Kini (Oxford Medical Genetics Laboratories) confirmed that WWOX should be on the epilepsy panel (personal communication via email on August 8th, 2019).
Proteinuric renal disease v1.221 LAMA5 Zornitza Stark reviewed gene: LAMA5: Rating: AMBER; Mode of pathogenicity: None; Publications: 29534211; Phenotypes: Nephrotic syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v1.195 AFF3 Rebecca Foulger Phenotypes for gene: AFF3 were changed from Intellectual disability; Seizures; Abnormality of skeletal morphology; Abnormality of the urinary system; Hypertrichosis; Abnormality of the respiratory system to Intellectual disability; Seizures; KINSSHIP syndrome
Genetic epilepsy syndromes v1.194 PIGU Rebecca Foulger commented on gene: PIGU
Genetic epilepsy syndromes v1.194 PIGU Rebecca Foulger Tag missense tag was added to gene: PIGU.
Genetic epilepsy syndromes v1.194 GRIA2 Rebecca Foulger commented on gene: GRIA2: GRIA2 is not yet associated with a disorder in OMIM or Gene2Phenotype.
Genetic epilepsy syndromes v1.194 GRIA2 Rebecca Foulger commented on gene: GRIA2: PMID:8938126 (animal model): GluR2 heterozygous (+/−) mice showed reduced motor coordination but no sign of seizure activity as measured by observation, EEG, or post-mortem analysis.
Genetic epilepsy syndromes v1.194 GRIA2 Rebecca Foulger Phenotypes for gene: GRIA2 were changed from Intellectual disability; Seizures; Autism to Intellectual disability; Seizures; myoclonic seizures; status epilepticus; tonic-clonic seizures; focal seizures
Genetic epilepsy syndromes v1.193 GRIA2 Rebecca Foulger commented on gene: GRIA2
Intellectual disability v2.996 GRIA2 Konstantinos Varvagiannis reviewed gene: GRIA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31300657; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic epilepsy syndromes v1.193 GRIA2 Konstantinos Varvagiannis gene: GRIA2 was added
gene: GRIA2 was added to Genetic epilepsy syndromes. Sources: Literature
Mode of inheritance for gene: GRIA2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: GRIA2 were set to 31300657
Phenotypes for gene: GRIA2 were set to Intellectual disability; Seizures; Autism
Penetrance for gene: GRIA2 were set to unknown
Review for gene: GRIA2 was set to AMBER
Added comment: There is a recent publication by Salpietro et al. (2019 - PMID: 31300657) reporting on 28 unrelated individuals. Seizures were observed in 12/28 (~40%), so the gene may also be relevant for the current panel.

The phenotype overall corresponds to a NDD disorder with DD, ID (universal feature in those with appropriate age for evaluation, relevant severity), ASD, Rett-like features and seizures. All types of variants were reported (15 missense, 2 splice-site, 1 in-frame del, 1 stopgain, 2 frameshift ones, 3 CNVs spanning GRIA2 and other genes, the latter more tolerant to LoF). The role of this gene (encoding AMPA receptor GluA2 subunit), functional studies (loss of function demonstrated for the majority of mutations, though by multiple molecular mechanisms), overlapping phenotype with disorders due to other ionotropic glutamate receptor subunit genes (eg. GRIA3/4 - ID with or without seizures), animal models (PMID cited: 8938126) are among the arguments provided.
Sources: Literature
Genetic epilepsy syndromes v1.193 AFF3 Konstantinos Varvagiannis gene: AFF3 was added
gene: AFF3 was added to Genetic epilepsy syndromes. Sources: Literature
Mode of inheritance for gene: AFF3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: AFF3 were set to https://doi.org/10.1101/693937; 18616733
Phenotypes for gene: AFF3 were set to Intellectual disability; Seizures; Abnormality of skeletal morphology; Abnormality of the urinary system; Hypertrichosis; Abnormality of the respiratory system
Penetrance for gene: AFF3 were set to unknown
Mode of pathogenicity for gene: AFF3 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: AFF3 was set to GREEN
Added comment: Voisin et al. (2019 - https://doi.org/10.1101/693937) report on 10 individuals with de novo missense AFF3 variants affecting a 9-amino-acid sequence (degron) important for the protein's degradation and summarize the phenotype of an additional individual previously described by Steichen-Gersdorf et al. (2008 - PMID: 18616733) with a 500 kb affecting only AFF3 (LAF4) and removing also this sequence.

The phenotype of missense variants consisted of kidney anomalies, mesomelic dysplasia, seizures, hypertrichosis, intellectual disability and pulmonary problems and was overlapping with that of the deletion. [10 of 11 subjects exhibited severe developmental epileptic encephalopathy].

9 probands harbored missense variants affecting the codon 258 while one individual had a variant affecting codon 260 [c.772G>T or p.Ala258Ser (x2), c.772G>A or p.Ala258Thr (x6), c.773C>T or p.Ala258Val (x1) and c.779T>G or p.(Val260Gly) (x1) - NM_001025108.1 / NP_001020279.1]. The deletion removed exons 4-13.

AFF1-4 are ALF transcription factor paralogs, components of the transcriptional super elongation complex regulating expression of genes involved in neurogenesis and development.

Using HEK293T cells expressing FLAG-tagged AFF3 (and AFF4) wt or mutants, accumulation of mutated forms was shown upon immunoblot.

Aff3+/- and/or -/- mice exhibit skeletal defects. These were more pronounced in homozygous mice which demonstrated also some elements in favor of kidney dysfunction and/or metabolic deregulation and possible neurological dysfunction (signs of impaired hearing and diminished grip strength). Homozygous mice had CNS anomalies (enlarged lateral ventricles and decreased corpus callosum size) similar to some affected individuals, although these were not observed in another Aff3-/- model. Knock-in mice modeling the microdeletion and the Ala258Thr variant displayed lower mesomelic limb deformities and early lethality respectively [cited PMIDs : 21677750, 25660031, knock-in model was part of the present study].

Accumulation of the protein in zebrafish (by overexpression of the human wt AFF3 mRNA), led to morphological defects.

Reanalysis of transcriptome data from previously generated HEK293T cell lines knocked down for AFF2, AFF3 and AFF4 by shRNAs (study) suggested that these transcription factors are not redundant.

Finally, CHOPS syndrome (#616368) due to mutations of AFF4 also leading to increased protein stability presents a partially overlapping phenotype (incl. cognitive impairment) to that of AFF3.
----
In G2P, AFF3 is associated with Skeletal dysplasia with severe neurological disease (disease confidence : probable / ID and seizures among the assigned phenotypes). There is no associated phenotype in OMIM.
----
As a result this gene can be considered for inclusion in the epilepsy panel as green (relevant phenotype and severity, sufficient cases, evidence for accumulation similar to AFF4, animal models, etc) or amber (pending publication of the article).
Sources: Literature
Intellectual disability v2.996 AFF3 Konstantinos Varvagiannis reviewed gene: AFF3: 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: https://doi.org/10.1101/693937, 18616733; Phenotypes: Intellectual disability, Seizures, Abnormality of skeletal morphology, Abnormality of the urinary system, Hypertrichosis, Abnormality of the respiratory system; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Genetic epilepsy syndromes v1.193 PIGU Konstantinos Varvagiannis gene: PIGU was added
gene: PIGU was added to Genetic epilepsy syndromes. Sources: Literature
Mode of inheritance for gene: PIGU was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGU were set to 31353022
Phenotypes for gene: PIGU were set to Global developmental delay; Intellectual disability; Seizures; Cerebral atrophy; Cerebellar hypoplasia; Scoliosis
Penetrance for gene: PIGU were set to Complete
Review for gene: PIGU was set to GREEN
Added comment: Knaus et al. (2019 - PMID: 31353022) report on 5 affected individuals (from 3 unrelated families) with biallelic pathogenic PIGU variants.

Common features included tone abnormalities, global DD, ID, seizures, CNS anomalies (cerebral atrophy and/or cerebellar hypoplasia), scoliosis. Affected individuals presented also with facial similarities. DD/ID were universal features and their severity appears to be relevant to the panel. Seizures were also reported in all individuals (myoclonic in 3, for whom this was specified). ALP was normal in all.

Three individuals from 2 non-consanguineous families (one from Norway, the other not specified) were homozygous for a missense variant NM_080476.4:c.1149C>A (or p.Asn383Lys) present with an AF of 7/277197 in Europeans. Two individuals born to consanguineous parents from Turkey were homozygous for another missense variant (c.209T>A or p.Ile70Lys - same RefSeq).

Segregation analyses in parents and unaffected sibs were carried out.

PIGU encodes a subunit of the GPI transaminidase, a heteropentameric complex (other subunits encoded by PIGK, PIGS, PIGT and GPAA1) that mediates attachment in the endoplasmic reticulum of glycosylphosphatidylinositol (GPI) to the C-termini of proteins which are subsequently anchored to the cell surface.

Pathogenic variants in 18 of 29 genes implicated in biosynthesis of the GPI anchor have been identified as a cause of GPI biosynthesis disorders, with ID and seizures as principal features. Mutations in other genes encoding components of the GPI transaminidase complex (GPAA1, PIGT and PIGS) lead to neurodevelopmental disorders.

Functional impairment of PIGU was supported by flow-cytometric analysis showing significant reduction of cell surface expression of GPI anchored proteins (mainly FLAER, CD16 and CD24) on granulocytes from affected individuals. In addition accumulation of free GPI anchors on the cell surface of B cells from affected individuals further suggested deficiency of the GPI transaminidase.

Transient expression of mutant (Asn383Lys) protein failed to rescue expression of GPI-APs to the same extent as wt in a CHO cell line deficient for PIGU.

Feature analysis demonstrated similarities among individuals with mutations in other genes of the GPI transamidase complex (GPAA1 and PIGT) as well as with GPI biosynthesis disorders. Facial analysis was also suggestive of facial similarities between individuals with GPAA1 and PIGU mutations.

PIGU is not associated with any phenotype in OMIM or G2P.

As a result this gene can be considered for inclusion in the ID and epilepsy panels probably as green (3 families, ID of relevant severity and seizures in all affected individuals, known group of disorders and supportive evidence) or amber.
Sources: Literature
Intellectual disability v2.996 PIGU Konstantinos Varvagiannis gene: PIGU was added
gene: PIGU was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: PIGU was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGU were set to 31353022
Phenotypes for gene: PIGU were set to Global developmental delay; Intellectual disability; Seizures; Cerebral atrophy; Cerebellar hypoplasia; Scoliosis
Penetrance for gene: PIGU were set to Complete
Review for gene: PIGU was set to GREEN
Added comment: Knaus et al. (2019 - PMID: 31353022) report on 5 affected individuals (from 3 unrelated families) with biallelic pathogenic PIGU variants.

Common features included tone abnormalities, global DD, ID, seizures, CNS anomalies (cerebral atrophy and/or cerebellar hypoplasia), scoliosis. Affected individuals presented also with facial similarities. DD/ID were universal features and their severity appears to be relevant to the panel. Seizures were also reported in all individuals (myoclonic in 3, for whom this was specified). ALP was normal in all.

Three individuals from 2 non-consanguineous families (one from Norway, the other not specified) were homozygous for a missense variant NM_080476.4:c.1149C>A (or p.Asn383Lys) present with an AF of 7/277197 in Europeans. Two individuals born to consanguineous parents from Turkey were homozygous for another missense variant (c.209T>A or p.Ile70Lys - same RefSeq).

Segregation analyses in parents and unaffected sibs were carried out.

PIGU encodes a subunit of the GPI transaminidase, a heteropentameric complex (other subunits encoded by PIGK, PIGS, PIGT and GPAA1) that mediates attachment in the endoplasmic reticulum of glycosylphosphatidylinositol (GPI) to the C-termini of proteins which are subsequently anchored to the cell surface.

Pathogenic variants in 18 of 29 genes implicated in biosynthesis of the GPI anchor have been identified as a cause of GPI biosynthesis disorders, with ID and seizures as principal features. Mutations in other genes encoding components of the GPI transaminidase complex (GPAA1, PIGT and PIGS) lead to neurodevelopmental disorders.

Functional impairment of PIGU was supported by flow-cytometric analysis showing significant reduction of cell surface expression of GPI anchored proteins (mainly FLAER, CD16 and CD24) on granulocytes from affected individuals. In addition accumulation of free GPI anchors on the cell surface of B cells from affected individuals further suggested deficiency of the GPI transaminidase.

Transient expression of mutant (Asn383Lys) protein failed to rescue expression of GPI-APs to the same extent as wt in a CHO cell line deficient for PIGU.

Feature analysis demonstrated similarities among individuals with mutations in other genes of the GPI transamidase complex (GPAA1 and PIGT) as well as with GPI biosynthesis disorders. Facial analysis was also suggestive of facial similarities between individuals with GPAA1 and PIGU mutations.

PIGU is not associated with any phenotype in OMIM or G2P.

As a result this gene can be considered for inclusion in the ID and epilepsy panels probably as green (3 families, ID of relevant severity and seizures in all affected individuals, known group of disorders and supportive evidence) or amber.
Sources: Literature
Genetic epilepsy syndromes v1.193 WDR37 Konstantinos Varvagiannis gene: WDR37 was added
gene: WDR37 was added to Genetic epilepsy syndromes. Sources: Literature
Mode of inheritance for gene: WDR37 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: WDR37 were set to 31327510; 31327508
Phenotypes for gene: WDR37 were set to Global developmental delay; Intellectual disability; Seizures; Abnormality of the eye; Abnormality of nervous system morphology; Hearing abnormality; Abnormality of the cardiovascular system; Abnormality of the skeletal system; Abnormality of the genitourinary system
Penetrance for gene: WDR37 were set to unknown
Mode of pathogenicity for gene: WDR37 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: WDR37 was set to GREEN
Added comment: Two concurrent publications by Reis et al. and Kanca et al. (2019 - PMIDs: 31327510, 31327508) report on the phenotype of individuals with de novo WDR37 mutations.

The study by Reis et al. provides clinical details on 4 affected individuals, while 5 further are described by Kanca et al.

4 different de novo variants were reported in these individuals who appear to be unrelated in (and between) the 2 studies [NM_014023.3]:
- c.356C>T (p.Ser119Phe) [Reis indiv. 1 - 3y, Kanca proband 3 - 5m2w]
- c.389C>T (p.Thr130Ile) [Reis indiv. 2 - 22m , Kanca proband 5 - 6 w]
- c.374C>T (p.Thr125Ile) [Reis indiv. 3 - 8y , Kanca proband 1 - 7y]
- c.386C>G (p.Ser129Cys) [Reis indiv. 4 - unkn age, Kanca probands 2 and 4, 6.5y and 19y]

Common features included DD/ID (severity relevant for the current panel), seizures (9/9), ocular anomalies (corneal opacity/Peters anomaly, coloboma, microphthalmia etc.) and variable brain, hearing, cardiovascular, skeletal and genitourinary anomalies. Some facial and/or other dysmorphic features (incl. excess nuchal skin / webbed neck) were also frequent among affected individuals. Feeding difficulties and growth deficiency were also among the features observed.

The function of WDR37 is not known. Variants demonstrated comparable protein levels and cellular localization compared to wt.

Reis et al. provide evidence using CRISPR-Cas9 mediated genome editing in zebrafish, to introduce the Ser129Cys variant observed in affected individuals as well as novel missense and frameshift variants. Poor growth (similar to the human phenotype) and larval lethality were noted for missense variants. Head size was proportionately small. Ocular (coloboma/corneal) or craniofacial anomalies were not observed. Zebrafish heterozygous for LoF variants survived to adulthood.

Based on these a dominant-negative mechanism was postulated for missense alleles.

RNA-seq analysis in zebrafish showed upregulation of cholesterol biosynthesis pathways (among the most dysregulated ones).

Previous data in mice, suggest a broad expression pattern for Wdr37 with enrichment in ocular and brain tissues, significant associations in homozygous mutant mice for decreased body weight, grip strength, skeletal anomalies and possible increase (p =< 0.05) in ocular (lens/corneal) and other anomalies [BioGPS and International Mouse Phenotyping Consortium cited].

CG12333 loss (the Drosophila WDR37 ortholog) causes increased bang sensitivity in flies (analogous to the human epilepsy phenotype), defects in copulation and grip strength, phenotypes that were rescued by human reference but not variant cDNAs.

As discussed by Kanca et al. based on data from Drosophila and mice, limited phenotypic similarity of CNVs spanning WDR37 and adjacent genes with the reported individuals and the presence of LoF variants in control populations haploinsufficiency appears unlikely. Gain-of-function is also unlikely, as expression of human variants in flies did not exacerbate the observed phenotypes. A dominant-negative effect is again proposed.

WDR37 is not associated with any phenotype in OMIM/G2P.

As a result WDR37 can be considered for inclusion in the ID and epilepsy panels with green (relevant phenotype, sufficient cases, animal models) or amber rating.
Sources: Literature
Intellectual disability v2.996 WDR37 Konstantinos Varvagiannis reviewed gene: WDR37: 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: 31327510, 31327508; Phenotypes: Global developmental delay, Intellectual disability, Seizures, Abnormality of the eye, Abnormality of nervous system morphology, Hearing abnormality, Abnormality of the cardiovascular system, Abnormality of the skeletal system, Abnormality of the genitourinary system; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v2.996 WDR37 Konstantinos Varvagiannis Deleted their review
Intellectual disability v2.996 WDR37 Konstantinos Varvagiannis gene: WDR37 was added
gene: WDR37 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: WDR37 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: WDR37 were set to 31327510; 31327508
Phenotypes for gene: WDR37 were set to Global developmental delay; Intellectual disability; Seizures; Abnormality of the eye; Abnormality of nervous system morphology; Hearing abnormality; Abnormality of the cardiovascular system; Abnormality of the skeletal system; Abnormality of the genitourinary system
Penetrance for gene: WDR37 were set to unknown
Review for gene: WDR37 was set to GREEN
Added comment: Two concurrent publications by Reis et al. and Kanca et al. (2019 - PMIDs: 31327510, 31327508) report on the phenotype of individuals with de novo WDR37 mutations.

The study by Reis et al. provides clinical details on 4 affected individuals, while 5 further are described by Kanca et al.

4 different de novo variants were reported in these individuals who appear to be unrelated in (and between) the 2 studies [NM_014023.3]:
- c.356C>T (p.Ser119Phe) [Reis indiv. 1 - 3y, Kanca proband 3 - 5m2w]
- c.389C>T (p.Thr130Ile) [Reis indiv. 2 - 22m , Kanca proband 5 - 6w]
- c.374C>T (p.Thr125Ile) [Reis indiv. 3 - 8y , Kanca proband 1 - 7y]
- c.386C>G (p.Ser129Cys) [Reis indiv. 4 - unkn age, Kanca probands 2 and 4, 6.5y and 19y]

Common features included DD/ID (severity relevant for the current panel), seizures (9/9), ocular anomalies (corneal opacity/Peters anomaly, coloboma, microphthalmia etc.) and variable brain, hearing, cardiovascular, skeletal and genitourinary anomalies. Some facial and/or other dysmorphic features (incl. excess nuchal skin / webbed neck) were also frequent among affected individuals. Feeding difficulties and growth deficiency were also among the features observed.

The function of WDR37 is not known. Variants demonstrated comparable protein levels and cellular localization compared to wt.

Reis et al. provide evidence using CRISPR-Cas9 mediated genome editing in zebrafish, to introduce the Ser129Cys variant observed in affected individuals as well as novel missense and frameshift variants. Poor growth (similar to the human phenotype) and larval lethality were noted for missense variants. Head size was proportionately small. Ocular (coloboma/corneal) or craniofacial anomalies were not observed. Zebrafish heterozygous for LoF variants survived to adulthood.

Based on these a dominant-negative mechanism was postulated for missense alleles.

RNA-seq analysis in zebrafish showed upregulation of cholesterol biosynthesis pathways (among the most dysregulated ones).

Previous data in mice, suggest a broad expression pattern for Wdr37 with enrichment in ocular and brain tissues, significant associations in homozygous mutant mice for decreased body weight, grip strength, skeletal anomalies and possible increase (p =< 0.05) in ocular (lens/corneal) and other anomalies [BioGPS and International Mouse Phenotyping Consortium cited].

CG12333 loss (the Drosophila WDR37 ortholog) causes increased bang sensitivity in flies (analogous to the human epilepsy phenotype), defects in copulation and grip strength, phenotypes that were rescued by human reference but not variant cDNAs.

As discussed by Kanca et al. based on data from Drosophila and mice, limited phenotypic similarity of CNVs spanning WDR37 and adjacent genes with the reported individuals and the presence of LoF variants in control populations haploinsufficiency appears unlikely. Gain-of-function is also unlikely, as expression of human variants in flies did not exacerbate the observed phenotypes. A dominant-negative effect is again proposed.

WDR37 is not associated with any phenotype in OMIM/G2P.

As a result WDR37 can be considered for inclusion in the ID and epilepsy panels with green (relevant phenotype, sufficient cases, animal models) or amber rating.
Sources: Literature
Hearing loss v1.122 GJB2 Eleanor Williams edited their review of gene: GJB2: Added comment: Adding publication PMID: 31160754 Shen et al 2019 Consensus interpretation of the p.Met34Thr and p.Val37Ile variants in GJB2 by the ClinGen Hearing Loss Expert Panel as additional information.; Changed rating: AMBER; Changed publications: 31160754
Limb disorders v1.53 FAM92A Eleanor Williams Classified gene: FAM92A as Amber List (moderate evidence)
Limb disorders v1.53 FAM92A Eleanor Williams Added comment: Comment on list classification: Promoted from red to amber. 1 case plus a mouse knockout showing a similar phenotype.
Limb disorders v1.53 FAM92A Eleanor Williams Gene: fam92a has been classified as Amber List (Moderate Evidence).
Limb disorders v1.52 FAM92A Eleanor Williams commented on gene: FAM92A: Provisionally associated with ?Polydactyly, postaxial, type A9 (#618219) in OMIM.

PMID: 30395363 - Schrauwen et al. 2018 - 1 case. They report a consanguineous Pakistani family with 3 children with
autosomal recessive nonsyndromic postaxial polydactyly type A. Blood was taken from 3 affected and 3 non-affected idividuals. DNA from one child was used for exome sequencing and revealed a homozygous nonsense variant (NM_001283034.1:c.478C>T, NP_001269963.1: p.[Arg160*]) in the FAM92A gene. Sanger sequencing confirmed that this variant segregates with PAPA. The c.478C>T variant (rs368652620) was observed in the gnomAD database with a very low MAF in the exome data (all populations MAF=2.04×10−5, South East Asians MAF=6.55×10−5 and no homozygous individuals observed and ) and was also not present in Sanger sequence data from 186 in-house control Pakistani DNAs. It is predicted to be targeted by the classical nonsense-mediated decay pathway. In mouse studies, FAM92A is expressed in the developing mouse limb and Fam92a−/− homozygous mice also exhibit an abnormal digit morphology, including metatarsal osteomas and polysyndactyly, in addition to distinct abnormalities on the deltoid tuberosity of their humeri.


we performed genomewide genotyping, linkage analysis, and exome and Sanger sequencing. Exome sequencing revealed a homozygous nonsense variant (c.478C>T, p.[Arg160*]) in the FAM92A gene within the mapped region on 8q21.13-q24.12 that segregated with the PAPA phenotype.

In 3 Pakistani brothers with postaxial polydactyly type A9 (PAPA9; 618219), identified homozygosity for a nonsense mutation in the FAM92A gene (R160X; 617273.0001) that segregated with disease and was not found in 186 Pakistani controls.


▼ Animal Model
Schrauwen et al. (2018) generated Fam92a -/- mice and observed extra bone growth or exostosis on the deltoid tuberosity of the humerus, consistent with tendon calcification. Abnormal digit morphology was significantly enriched in the mutant mice compared to controls, and included polysyndactyly and osteomas
Familial non syndromic congenital heart disease v1.48 Ellen McDonagh Panel types changed to Rare Disease 100K
Limb disorders v1.52 GLI1 Eleanor Williams Publications for gene: GLI1 were set to 28973407; 28973407
Limb disorders v1.51 GLI1 Eleanor Williams Phenotypes for gene: GLI1 were changed from Polydactyly, postaxial, type A8, 618123); Polydactyly, preaxial I, 174400 to Polydactyly, postaxial, type A8, 618123; Polydactyly, preaxial I, 174400
Limb disorders v1.50 GLI1 Eleanor Williams Phenotypes for gene: GLI1 were changed from to Polydactyly, postaxial, type A8, 618123); Polydactyly, preaxial I, 174400
Limb disorders v1.49 GLI1 Eleanor Williams changed review comment from: Comment on list classification: >3 cases of variants in GLI1 in families with polydactyly; to: Comment on list classification: Changing rating from red to green. >3 cases of variants in GLI1 in families with polydactyly
Limb disorders v1.49 GLI1 Eleanor Williams Classified gene: GLI1 as Green List (high evidence)
Limb disorders v1.49 GLI1 Eleanor Williams Added comment: Comment on list classification: >3 cases of variants in GLI1 in families with polydactyly
Limb disorders v1.49 GLI1 Eleanor Williams Gene: gli1 has been classified as Green List (High Evidence).
Familial non syndromic congenital heart disease v1.47 Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Limb disorders v1.48 GLI1 Eleanor Williams changed review comment from: Associated with Polydactyly, postaxial, type A8 (#618123) and Polydactyly, preaxial I (#174400) in OMIM.

Postaxial Polydactyly Type A8:
PMID: 28973407 - Palencia-Campos et al. 2017- 3 cases. They report data from 3 families, 2 Turkish (1 consangineous),1 Pakistani (consangineous) with developmental defects overlapping with Ellis–van Creveld syndrome, including postaxial polydactyly of the hands and/or feet . Homozygous truncating mutations (NM_005269.2: c.2340G > A; p.Trp780*, NM_005269.2: c.1930C > T; p.Gln644*, NM_005269.2: c.337C > T; p.Arg113*) were identified in patients in all 3 families.
Note, in the extended members of family 1, one individual is reported with polydactyly but is heterozygous for the p.Trp780* variant and one individual with polydactyly but no p.Trp780* variant is reported (possible different homozygous genetic alteration not detectable by exome sequencing?).

Polydactyly, preaxial I:
PMID: 30620395 - Ullah et al. 2019 - 1 case. Pakistani family segregating autosomal recessive form of pre‐axial polydactyly. 2 individuals from two parts of the family were sequenced and a novel homozygous missense mutation identified c.1517T>A; p.Leu506Gln) in the GLI1. The variant segregated with the disease phenotype in the family.
It was not found in their in‐house exome sequence data from 70 additional unrelated Pakistani individuals with normal limb phenotypes but was found in heterozygous state in the gnomAD browser, with an allele frequency of 0.0002109, but not in homozygous state.; to: Associated with Polydactyly, postaxial, type A8 (#618123) and Polydactyly, preaxial I (#174400) in OMIM.

Postaxial Polydactyly Type A8:
PMID: 28973407 - Palencia-Campos et al. 2017- 3 cases. They report data from 3 families, 2 Turkish (1 consangineous),1 Pakistani (consangineous) with developmental defects overlapping with Ellis–van Creveld syndrome, including postaxial polydactyly of the hands and/or feet . Homozygous truncating mutations (NM_005269.2: c.2340G > A; p.Trp780*, NM_005269.2: c.1930C > T; p.Gln644*, NM_005269.2: c.337C > T; p.Arg113*) were identified in patients in all 3 families.
Note, in the extended members of family 1, one individual is reported with polydactyly but is heterozygous for the p.Trp780* variant (patient 3) and one individual with polydactyly but no p.Trp780* variant is reported (patient 4). Homozygosity mapping suggests that these results were consistent with GLI1-W780X being responsible for the phenotype of patients 1–2 and a different genetic variation or disease mechanism for the phenotypes of patients 3 and 4.

Polydactyly, preaxial I:
PMID: 30620395 - Ullah et al. 2019 - 1 case. Pakistani family segregating autosomal recessive form of pre‐axial polydactyly. 2 individuals from two parts of the family were sequenced and a novel homozygous missense mutation identified c.1517T>A; p.Leu506Gln) in the GLI1. The variant segregated with the disease phenotype in the family. It was not found in their in‐house exome sequence data from 70 additional unrelated Pakistani individuals with normal limb phenotypes but was found in heterozygous state in the gnomAD browser, with an allele frequency of 0.0002109, but not in homozygous state.
Congenital myopathy v1.152 KLHL9 Ivone Leong Publications for gene: KLHL9 were set to 23746549
Limb disorders v1.48 GLI1 Eleanor Williams commented on gene: GLI1: Associated with Polydactyly, postaxial, type A8 (#618123) and Polydactyly, preaxial I (#174400) in OMIM.

Postaxial Polydactyly Type A8:
PMID: 28973407 - Palencia-Campos et al. 2017- 3 cases. They report data from 3 families, 2 Turkish (1 consangineous),1 Pakistani (consangineous) with developmental defects overlapping with Ellis–van Creveld syndrome, including postaxial polydactyly of the hands and/or feet . Homozygous truncating mutations (NM_005269.2: c.2340G > A; p.Trp780*, NM_005269.2: c.1930C > T; p.Gln644*, NM_005269.2: c.337C > T; p.Arg113*) were identified in patients in all 3 families.
Note, in the extended members of family 1, one individual is reported with polydactyly but is heterozygous for the p.Trp780* variant and one individual with polydactyly but no p.Trp780* variant is reported (possible different homozygous genetic alteration not detectable by exome sequencing?).

Polydactyly, preaxial I:
PMID: 30620395 - Ullah et al. 2019 - 1 case. Pakistani family segregating autosomal recessive form of pre‐axial polydactyly. 2 individuals from two parts of the family were sequenced and a novel homozygous missense mutation identified c.1517T>A; p.Leu506Gln) in the GLI1. The variant segregated with the disease phenotype in the family.
It was not found in their in‐house exome sequence data from 70 additional unrelated Pakistani individuals with normal limb phenotypes but was found in heterozygous state in the gnomAD browser, with an allele frequency of 0.0002109, but not in homozygous state.
Paediatric disorders v3.664 Ellen McDonagh Changed child panels to: Intellectual disability; Skeletal dysplasia; DDG2P; Inborn errors of metabolism; Limb disorders; Paediatric disorders - additional genes; Skeletal ciliopathies; Ophthalmological ciliopathies; Neurological ciliopathies; Renal ciliopathies
Congenital myaesthenic syndrome v1.52 SYT2 Ivone Leong Classified gene: SYT2 as Green List (high evidence)
Congenital myaesthenic syndrome v1.52 SYT2 Ivone Leong Added comment: Comment on list classification: Promoted from red to green. PMID: 30533528 reported on a third unrelated case with a new variant in this gene. Therefore there is enough evidence to support a gene-disease association.
Congenital myaesthenic syndrome v1.52 SYT2 Ivone Leong Gene: syt2 has been classified as Green List (High Evidence).
Congenital myaesthenic syndrome v1.51 SYT2 Ivone Leong Publications for gene: SYT2 were set to 26519543; 25192047; 27472506 (Review)
Paediatric disorders - additional genes v0.28 CFC1 Helen Brittain Classified gene: CFC1 as Green List (high evidence)
Paediatric disorders - additional genes v0.28 CFC1 Helen Brittain Added comment: Comment on list classification: Meets criteria for green rating in 100K - awaiting higher level sign off for GMS indication
Paediatric disorders - additional genes v0.28 CFC1 Helen Brittain Gene: cfc1 has been classified as Green List (High Evidence).
Paediatric disorders - additional genes v0.27 CFC1 Helen Brittain gene: CFC1 was added
gene: CFC1 was added to Paediatric disorders - additional genes. Sources: Literature
Mode of inheritance for gene: CFC1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CFC1 were set to 11062482; 11799476
Phenotypes for gene: CFC1 were set to Heterotaxy, visceral, 2, autosomal 605376
Review for gene: CFC1 was set to GREEN
Added comment: Three unrelated cases with laterality defects with two LOF mutations in PMID 11062482. Also PMID 11799476 reports two cases with congenital cardiac malformations (TGA/DORV). Considered sufficient cases for inclusion.
Sources: Literature
Congenital myaesthenic syndrome v1.50 ALG14 Ivone Leong Classified gene: ALG14 as Green List (high evidence)
Congenital myaesthenic syndrome v1.50 ALG14 Ivone Leong Added comment: Comment on list classification: Promoted from red to green. ALG14 is associated with a phenotype on OMIM and not on Gene2Phenotype. This gene was promoted to green gene status based on the additional evidence provided by the expert reviewer as there is now enough evidence to support a gene-disease association.
Congenital myaesthenic syndrome v1.50 ALG14 Ivone Leong Gene: alg14 has been classified as Green List (High Evidence).