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Congenital disorders of glycosylation v5.6 DDOST Achchuthan Shanmugasundram Gene: ddost has been classified as Amber List (Moderate Evidence).
Congenital disorders of glycosylation v5.5 DDOST Achchuthan Shanmugasundram Phenotypes for gene: DDOST were changed from ?Congenital disorder of glycosylation, type Ir 614507 to Congenital disorder of glycosylation, type Ir, OMIM:614507
Congenital disorders of glycosylation v5.4 DDOST Achchuthan Shanmugasundram Publications for gene: DDOST were set to 22305527
Congenital disorders of glycosylation v5.3 DDOST Achchuthan Shanmugasundram Tag Q3_24_promote_green tag was added to gene: DDOST.
Congenital disorders of glycosylation v5.3 DDOST Achchuthan Shanmugasundram reviewed gene: DDOST: Rating: GREEN; Mode of pathogenicity: None; Publications: 22305527, 34462534; Phenotypes: Congenital disorder of glycosylation, type Ir, OMIM:614507; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.9 MT-TY Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TY.
Likely inborn error of metabolism v5.22 MT-TY Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TY.
Undiagnosed metabolic disorders v1.620 MT-TY Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TY.
Mitochondrial disorders v6.9 MT-TW Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TW.
Likely inborn error of metabolism v5.22 MT-TW Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TW.
Undiagnosed metabolic disorders v1.620 MT-TW Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TW.
Mitochondrial disorders v6.9 MT-TV Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TV.
Likely inborn error of metabolism v5.22 MT-TV Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TV.
Undiagnosed metabolic disorders v1.620 MT-TV Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TV.
Retinal disorders v5.15 MT-TS2 Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TS2.
Mitochondrial disorders v6.9 MT-TS2 Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TS2.
Likely inborn error of metabolism v5.22 MT-TS2 Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TS2.
Undiagnosed metabolic disorders v1.620 MT-TS2 Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TS2.
Mitochondrial disorders v6.9 MT-TS1 Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TS1.
Monogenic hearing loss v4.50 MT-TS1 Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TS1.
Likely inborn error of metabolism v5.22 MT-TS1 Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TS1.
Undiagnosed metabolic disorders v1.620 MT-TS1 Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TS1.
Mitochondrial disorders v6.9 MT-TR Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TR.
Likely inborn error of metabolism v5.22 MT-TR Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TR.
Undiagnosed metabolic disorders v1.620 MT-TR Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TR.
Mitochondrial disorders v6.9 MT-TQ Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TQ.
Likely inborn error of metabolism v5.22 MT-TQ Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TQ.
Undiagnosed metabolic disorders v1.620 MT-TQ Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TQ.
Retinal disorders v5.15 MT-TP Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TP.
Mitochondrial disorders v6.9 MT-TP Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TP.
DDG2P v4.6 MT-TP Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TP.
Likely inborn error of metabolism v5.22 MT-TP Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TP.
Undiagnosed metabolic disorders v1.620 MT-TP Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TP.
Mitochondrial disorders v6.9 MT-TN Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TN.
Likely inborn error of metabolism v5.22 MT-TN Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TN.
Undiagnosed metabolic disorders v1.620 MT-TN Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TN.
Mitochondrial disorders v6.9 MT-TM Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TM.
Likely inborn error of metabolism v5.22 MT-TM Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TM.
Undiagnosed metabolic disorders v1.620 MT-TM Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TM.
Mitochondrial disorders v6.9 MT-TL2 Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TL2.
Likely inborn error of metabolism v5.22 MT-TL2 Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TL2.
Undiagnosed metabolic disorders v1.620 MT-TL2 Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TL2.
Hereditary neuropathy or pain disorder v4.11 MT-TL1 Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TL1.
Retinal disorders v5.15 MT-TL1 Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TL1.
Mitochondrial disorders v6.9 MT-TL1 Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TL1.
Hereditary neuropathy v1.480 MT-TL1 Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TL1.
Likely inborn error of metabolism v5.22 MT-TL1 Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TL1.
Undiagnosed metabolic disorders v1.620 MT-TL1 Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TL1.
Monogenic diabetes v2.58 MT-TL1 Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TL1.
Familial diabetes v1.67 MT-TL1 Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TL1.
Diabetes with additional phenotypes suggestive of a monogenic aetiology v1.67 MT-TL1 Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TL1.
Mitochondrial disorders v6.9 MT-TK Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TK.
Likely inborn error of metabolism v5.22 MT-TK Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TK.
Undiagnosed metabolic disorders v1.620 MT-TK Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TK.
Multiple lipomas v1.1 MT-TK Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TK.
Paediatric or syndromic cardiomyopathy v4.10 MT-TI Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TI.
Mitochondrial disorders v6.9 MT-TI Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TI.
Likely inborn error of metabolism v5.22 MT-TI Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TI.
Undiagnosed metabolic disorders v1.620 MT-TI Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TI.
Hypertrophic cardiomyopathy v4.13 MT-TI Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TI.
Retinal disorders v5.15 MT-TH Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TH.
Mitochondrial disorders v6.9 MT-TH Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TH.
Likely inborn error of metabolism v5.22 MT-TH Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TH.
Undiagnosed metabolic disorders v1.620 MT-TH Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TH.
Mitochondrial disorders v6.9 MT-TG Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TG.
Likely inborn error of metabolism v5.22 MT-TG Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TG.
Undiagnosed metabolic disorders v1.620 MT-TG Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TG.
Mitochondrial disorders v6.9 MT-TF Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TF.
Likely inborn error of metabolism v5.22 MT-TF Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TF.
Undiagnosed metabolic disorders v1.620 MT-TF Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TF.
Unexplained young onset end-stage renal disease v4.7 MT-TF Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TF.
Tubulointerstitial kidney disease v3.3 MT-TF Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TF.
Mitochondrial disorders v6.9 MT-TE Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TE.
Likely inborn error of metabolism v5.22 MT-TE Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TE.
Undiagnosed metabolic disorders v1.620 MT-TE Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TE.
Mitochondrial disorders v6.9 MT-TD Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TD.
Likely inborn error of metabolism v5.22 MT-TD Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TD.
Undiagnosed metabolic disorders v1.620 MT-TD Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TD.
Mitochondrial disorders v6.9 MT-TC Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TC.
Likely inborn error of metabolism v5.22 MT-TC Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TC.
Undiagnosed metabolic disorders v1.620 MT-TC Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TC.
Fetal anomalies v4.27 MIR17HG Sarah Leigh Tag locus-type-rna-long-non-coding tag was added to gene: MIR17HG.
Likely inborn error of metabolism v5.22 MT-RNR1 Sarah Leigh Tag locus-type-rna-ribosomal tag was added to gene: MT-RNR1.
Likely inborn error of metabolism v5.22 MT-TA Sarah Leigh Tag locus-type-rna-transfer tag was added to gene: MT-TA.
Hereditary neuropathy v1.480 MT-RNR1 Sarah Leigh Tag locus-type-rna-ribosomal tag was added to gene: MT-RNR1.
Congenital adrenal hypoplasia v3.11 ABCD1 Dmitrijs Rots reviewed gene: ABCD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Adrenoleukodystrophy, Adrenomyeloneuropathy, adult; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males); Current diagnostic: yes
Early onset or syndromic epilepsy v5.24 CNTN2 Achchuthan Shanmugasundram Classified gene: CNTN2 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v5.24 CNTN2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Sarah Graham, there is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.
Early onset or syndromic epilepsy v5.24 CNTN2 Achchuthan Shanmugasundram Gene: cntn2 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v5.23 CNTN2 Achchuthan Shanmugasundram Phenotypes for gene: CNTN2 were changed from Epilepsy, familial adult myoclonic, 5 to Epilepsy, early-onset, 5, with or without developmental delay, OMIM:615400
Early onset or syndromic epilepsy v5.22 CNTN2 Achchuthan Shanmugasundram Publications for gene: CNTN2 were set to
Early onset or syndromic epilepsy v5.21 CNTN2 Achchuthan Shanmugasundram Mode of inheritance for gene: CNTN2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.20 CNTN2 Achchuthan Shanmugasundram Tag Q3_24_promote_green tag was added to gene: CNTN2.
Tag Q3_24_NHS_review tag was added to gene: CNTN2.
Early onset or syndromic epilepsy v5.20 CNTN2 Achchuthan Shanmugasundram edited their review of gene: CNTN2: Added comment: PMID:23518707 reported a consanguineous Egyptian family in which five siblings aged 11 to 14 years had seizures and were identified with a homozygous frameshift CNTN2 variant (p.Trp168fs).

PMID:34691156 reported a 10-year old boy born of unrelated parents of Han Chinese descent, with developmental delay and onset of generalised tonic-clonic seizures at 5 years of age and identified with a homozygous frameshift CNTN2 variant (p.Thr958Thrfs).

PMID:36553572 reported a 13-year-old boy with global developmental delay and epileptic encephalopathy and was associated with a homozygous nonsense variant (p.Arg314Ter) in the CNTN2 gene.

PMID:37359369 reported a consanguineous Pakistani family in which four siblings developed various types of seizures late in the first decade of their life and had global developmental,ental delay with mild intellectual disability. They were identified with a homozygous nonsense CNTN2 variant (p.Glu567Ter)

This gene has been associated with relevant phenotypes in OMIM (MIM #615400), but not yet in Gene2Phenotype.; Changed publications to: 23518707, 34691156, 36553572, 37359369
Intellectual disability v6.52 MSL2 Nour Elkhateeb reviewed gene: MSL2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38815585, 38702431; Phenotypes: Developmental delay, intellectual disability, autism spectrum disorder, hypotonia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v5.20 CNTN2 Achchuthan Shanmugasundram reviewed gene: CNTN2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Epilepsy, early-onset, 5, with or without developmental delay, OMIM:615400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v6.52 TBC1D7 Achchuthan Shanmugasundram Tag watchlist was removed from gene: TBC1D7.
Tag Q3_24_promote_green tag was added to gene: TBC1D7.
Tag Q3_24_NHS_review tag was added to gene: TBC1D7.
Intellectual disability v6.52 TBC1D7 Achchuthan Shanmugasundram Classified gene: TBC1D7 as Amber List (moderate evidence)
Intellectual disability v6.52 TBC1D7 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Frances Elmslie, PMID:36669495 reported an additional case with compound heterozygous variants (identified via trio RNA-Seq) and presenting with a neurodevelopmental disorder involving mild intellectual disability.

Hence, this gene can be promoted to green rating with the current evidence (three unrelated cases and functional studies) in the next GMS update.
Intellectual disability v6.52 TBC1D7 Achchuthan Shanmugasundram Gene: tbc1d7 has been classified as Amber List (Moderate Evidence).
Intellectual disability v6.51 TBC1D7 Achchuthan Shanmugasundram Publications for gene: TBC1D7 were set to PMID: 23687350; 24515783
Intellectual disability v6.50 TBC1D7 Achchuthan Shanmugasundram reviewed gene: TBC1D7: Rating: GREEN; Mode of pathogenicity: None; Publications: 36669495; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 ARSA Alexander Rossor edited their review of gene: ARSA: Added comment: Peripheral neuropathy is a well recognised feature of metachromatic leukodystrophy; Changed publications to: 31684987; Changed phenotypes to: Metachromatic leukodystrophy. Severe late infantile form with mental retardation and severe course. Regression before 30 months, adult onset, psychiatric symptoms, leukodystrophy on MRI, progressive neuropathy with SNCV, optic atrophy
Hereditary neuropathy or pain disorder v4.11 APTX Alexander Rossor edited their review of gene: APTX: Added comment: APTX recessive variants are a well established cause of cerebellar ataxia and peripheral neuropathy; Changed rating: GREEN; Changed publications to: 11176957
Fetal hydrops v1.86 GATA1 Sarah Leigh Phenotypes for gene: GATA1 were changed from Anaemia, X-linked, with/without neutropaenia and/or platelet abnormalities, MIM#300835 to Anaemia, X-linked, with/without neutropaenia and/or platelet abnormalities, OMIM:300835; Hemolytic anemia due to elevated adenosine deaminase, OMIM:301083
Fetal hydrops v1.85 GATA1 Sarah Leigh Publications for gene: GATA1 were set to 10700180; 33082562
Fetal hydrops v1.84 GATA1 Sarah Leigh Classified gene: GATA1 as Green List (high evidence)
Fetal hydrops v1.84 GATA1 Sarah Leigh Gene: gata1 has been classified as Green List (High Evidence).
Fetal hydrops v1.83 GATA1 Sarah Leigh reviewed gene: GATA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301538, 30914438, 29949202, 35580337; Phenotypes: Hemolytic anemia due to elevated adenosine deaminase, OMIM:301083; Mode of inheritance: None
Fetal hydrops v1.83 GATA1 Sarah Leigh Publications for gene: GATA1 were set to 10700180
Fetal hydrops v1.82 G6PD Sarah Leigh Publications for gene: G6PD were set to 33082562
Fetal hydrops v1.81 G6PD Sarah Leigh reviewed gene: G6PD: Rating: AMBER; Mode of pathogenicity: None; Publications: 23719252; Phenotypes: ; Mode of inheritance: None
Fetal hydrops v1.81 G6PD Sarah Leigh Publications for gene: G6PD were set to PMID: 33082562
Fetal hydrops v1.80 G6PD Sarah Leigh Classified gene: G6PD as Amber List (moderate evidence)
Fetal hydrops v1.80 G6PD Sarah Leigh Gene: g6pd has been classified as Amber List (Moderate Evidence).
Fetal anomalies v4.27 FZD6 Sarah Leigh Phenotypes for gene: FZD6 were changed from NAIL DISORDER NON-SYNDROMIC CONGENITAL TYPE 10 to Nail disorder, nonsyndromic congenital, 1, OMIM:161050
Fetal anomalies v4.26 FZD6 Sarah Leigh Publications for gene: FZD6 were set to
Fetal anomalies v4.25 FZD6 Sarah Leigh Classified gene: FZD6 as Amber List (moderate evidence)
Fetal anomalies v4.25 FZD6 Sarah Leigh Gene: fzd6 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v4.24 FZD6 Sarah Leigh reviewed gene: FZD6: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal hydrops v1.79 FZD6 Sarah Leigh Classified gene: FZD6 as Amber List (moderate evidence)
Fetal hydrops v1.79 FZD6 Sarah Leigh Gene: fzd6 has been classified as Amber List (Moderate Evidence).
Fetal hydrops v1.78 FZD6 Sarah Leigh reviewed gene: FZD6: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal hydrops v1.78 FZD6 Sarah Leigh Phenotypes for gene: FZD6 were changed from Nonimmune hydrops fetalis to Nail disorder, nonsyndromic congenital, 1, OMIM:161050
Fetal hydrops v1.77 FZD6 Sarah Leigh Mode of inheritance for gene: FZD6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Fetal hydrops v1.76 FZD6 Sarah Leigh Publications for gene: FZD6 were set to 33082562; 26036949
Fetal hydrops v1.75 FZD6 Sarah Leigh Publications for gene: FZD6 were set to 33082562; 26036949
Fetal hydrops v1.74 FZD6 Sarah Leigh Publications for gene: FZD6 were set to 33082562
Fetal hydrops v1.73 FZD6 Sarah Leigh Publications for gene: FZD6 were set to PMID: 33082562
Fetal hydrops v1.72 CDC42 Sarah Leigh reviewed gene: CDC42: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Fetal hydrops v1.72 CDC42 Sarah Leigh Classified gene: CDC42 as Amber List (moderate evidence)
Fetal hydrops v1.72 CDC42 Sarah Leigh Gene: cdc42 has been classified as Amber List (Moderate Evidence).
Fetal hydrops v1.71 CDC42 Sarah Leigh Publications for gene: CDC42 were set to 3308256229335451; 26708094
Fetal hydrops v1.70 CDC42 Sarah Leigh Publications for gene: CDC42 were set to 33082562
Fetal hydrops v1.69 CDC42 Sarah Leigh Publications for gene: CDC42 were set to PMID: 33082562
Fetal hydrops v1.68 CANT1 Sarah Leigh Classified gene: CANT1 as Green List (high evidence)
Fetal hydrops v1.68 CANT1 Sarah Leigh Gene: cant1 has been classified as Green List (High Evidence).
Fetal anomalies v4.24 ANGPT2 Sarah Leigh Entity copied from Fetal hydrops v1.67
Fetal anomalies v4.24 ANGPT2 Sarah Leigh gene: ANGPT2 was added
gene: ANGPT2 was added to Fetal anomalies. Sources: Literature,Expert Review Amber
Mode of inheritance for gene: ANGPT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ANGPT2 were set to 32908006; 34876502
Phenotypes for gene: ANGPT2 were set to Lymphatic malformation 10 OMIM:619369; lymphatic malformation 10 MONDO:0023662
Fetal hydrops v1.67 ANGPT2 Sarah Leigh Mode of inheritance for gene: ANGPT2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Fetal hydrops v1.66 ANGPT2 Sarah Leigh Mode of inheritance for gene: ANGPT2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal hydrops v1.65 ALPK3 Sarah Leigh Classified gene: ALPK3 as Green List (high evidence)
Fetal hydrops v1.65 ALPK3 Sarah Leigh Gene: alpk3 has been classified as Green List (High Evidence).
Fetal hydrops v1.64 ALPK3 Sarah Leigh reviewed gene: ALPK3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cardiomyopathy, familial hypertrophic 27, OMIM:618052; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.20 CNTN2 Sarah Graham reviewed gene: CNTN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 37359369, 34691156, 28397838, 36553572; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteopetrosis v1.34 TYROBP Ian Berry reviewed gene: TYROBP: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Membranoproliferative glomerulonephritis including C3 glomerulopathy v3.3 DGKE Achchuthan Shanmugasundram Tag for-review was removed from gene: DGKE.
Tag to_be_confirmed_NHSE was removed from gene: DGKE.
Membranoproliferative glomerulonephritis including C3 glomerulopathy v3.3 CFH Achchuthan Shanmugasundram Tag for-review was removed from gene: CFH.
Tag to_be_confirmed_NHSE was removed from gene: CFH.
Acute rhabdomyolysis v1.18 CYP2C8 Achchuthan Shanmugasundram changed review comment from: The rating of this gene remains red as the MOI is unknown and rhabdomyolysis is drug-induced rather than inherited.; to: The rating of this gene remains red as the MOI is unknown and rhabdomyolysis is drug-induced rather than inherited.
Acute rhabdomyolysis v1.18 CYP2C8 Achchuthan Shanmugasundram reviewed gene: CYP2C8: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v6.50 TBC1D7 Frances Elmslie reviewed gene: TBC1D7: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 24515783, 23687350, 36669495, 35584673; Phenotypes: Macrocephaly, intellectual disability, megalencephaly; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Acute rhabdomyolysis v1.18 CYP2C8 Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE was removed from gene: CYP2C8.
Intellectual disability v6.50 RNU4-2 Arina Puzriakova changed review comment from: Greene et al. 2024 (PMID: 38821540) reported on 73 unrelated cases with a neurodevelopmental disorder associated with heterozygous variants in the RNU4-2 gene, overlapping findings in PMID:38645094 (still currently in preprint). Participants were identified through their enrolment in various cohorts including the 100,000 Genomes Project, NHSE Genomic Medicine Service (GMS), and NIHR BioResource.

Almost all variants were acquired de novo, with the exception of one variant that was inherited from an affected mother and 16 probands with unknown inheritance due to lack of parental genotype data.
Variants cluster in two regions of RNU4-2 (n.62–70 and n.73–79) but the majority of cases harboured a recurrent variant, n.64_65insT.

Clinical presentation was predominantly characterised by intellectual disability, but other observed features include microcephaly, proportionate short stature, hypotonia, seizures and motor delay.; to: Greene et al. 2024 (PMID: 38821540) reported on 73 unrelated cases with a neurodevelopmental disorder associated with heterozygous variants in the RNU4-2 gene, overlapping findings in PMID: 38645094 (still currently in preprint). Participants were identified through their enrolment in various cohorts including the 100,000 Genomes Project, NHSE Genomic Medicine Service (GMS), and NIHR BioResource.

Almost all variants were acquired de novo, with the exception of one variant that was inherited from an affected mother and 16 probands with unknown inheritance due to lack of parental genotype data.
Variants cluster in two regions of RNU4-2 (n.62–70 and n.73–79) but the majority of cases harboured a recurrent variant, n.64_65insT.

Clinical presentation was predominantly characterised by intellectual disability, but other observed features include microcephaly, proportionate short stature, hypotonia, seizures and motor delay.
Early onset or syndromic epilepsy v5.20 RNU4-2 Arina Puzriakova changed review comment from: Greene et al. 2024 (PMID: 38821540) reported on 73 unrelated cases with a neurodevelopmental disorder associated with heterozygous variants in the RNU4-2 gene, overlapping findings in PMID:38645094 (still currently in preprint). Participants were identified through their enrolment in various cohorts including the 100,000 Genomes Project, NHSE Genomic Medicine Service (GMS), and NIHR BioResource.

Almost all variants were acquired de novo, with the exception of one variant that was inherited from an affected mother and 16 probands with unknown inheritance due to lack of parental genotype data.
Variants cluster in two regions of RNU4-2 (n.62–70 and n.73–79) but the majority of cases harboured a recurrent variant, n.64_65insT.

Clinical presentation was predominantly characterised by intellectual disability, but other observed features include microcephaly, proportionate short stature, hypotonia, seizures and motor delay.; to: Greene et al. 2024 (PMID: 38821540) reported on 73 unrelated cases with a neurodevelopmental disorder associated with heterozygous variants in the RNU4-2 gene, overlapping findings in PMID: 38645094 (still currently in preprint). Participants were identified through their enrolment in various cohorts including the 100,000 Genomes Project, NHSE Genomic Medicine Service (GMS), and NIHR BioResource.

Almost all variants were acquired de novo, with the exception of one variant that was inherited from an affected mother and 16 probands with unknown inheritance due to lack of parental genotype data.
Variants cluster in two regions of RNU4-2 (n.62–70 and n.73–79) but the majority of cases harboured a recurrent variant, n.64_65insT.

Clinical presentation was predominantly characterised by intellectual disability, but other observed features include microcephaly, proportionate short stature, hypotonia, seizures and motor delay.
Severe microcephaly v5.15 RNU4-2 Arina Puzriakova changed review comment from: Greene et al. 2024 (PMID: 38821540) reported on 73 unrelated cases with a neurodevelopmental disorder associated with heterozygous variants in the RNU4-2 gene, overlapping findings in PMID:38645094 (still currently in preprint). Participants were identified through their enrolment in various cohorts including the 100,000 Genomes Project, NHSE Genomic Medicine Service (GMS), and NIHR BioResource.

Almost all variants were acquired de novo, with the exception of one variant that was inherited from an affected mother and 16 probands with unknown inheritance due to lack of parental genotype data.
Variants cluster in two regions of RNU4-2 (n.62–70 and n.73–79) but the majority of cases harboured a recurrent variant, n.64_65insT.

Clinical presentation was predominantly characterised by intellectual disability, but other observed features include microcephaly, proportionate short stature, hypotonia, seizures and motor delay.; to: Greene et al. 2024 (PMID: 38821540) reported on 73 unrelated cases with a neurodevelopmental disorder associated with heterozygous variants in the RNU4-2 gene, overlapping findings in PMID: 38645094 (still currently in preprint). Participants were identified through their enrolment in various cohorts including the 100,000 Genomes Project, NHSE Genomic Medicine Service (GMS), and NIHR BioResource.

Almost all variants were acquired de novo, with the exception of one variant that was inherited from an affected mother and 16 probands with unknown inheritance due to lack of parental genotype data.
Variants cluster in two regions of RNU4-2 (n.62–70 and n.73–79) but the majority of cases harboured a recurrent variant, n.64_65insT.

Clinical presentation was predominantly characterised by intellectual disability, but other observed features include microcephaly, proportionate short stature, hypotonia, seizures and motor delay.
Intellectual disability v6.50 RNU4-2 Arina Puzriakova changed review comment from: Comment on list classification: The two papers (PMID: 38821540; 38645094) corroborate mutual findings and report over 100 unrelated individuals with a clinically overlapping neurological disorder and variants the non-coding gene RNU4-2.

Overall there is sufficient evidence to promote this gene to Green status at the next GMS panel update.; to: Comment on list classification: Multiple individuals have been identified in PMID: 38821540 with a clinically overlapping neurological disorder and variants the non-coding gene RNU4-2. Additional cases with mutual findings have also been reported in PMID: 38645094, corroborating this gene-disease association - however, PMID: 38645094 is still in preprint at this time.

Overall there is sufficient evidence to promote this gene to Green status at the next GMS panel update.
Early onset or syndromic epilepsy v5.20 RNU4-2 Arina Puzriakova changed review comment from: Comment on list classification: The two papers (PMID: 38821540; 38645094) corroborate mutual findings and report over 100 unrelated individuals with a clinically overlapping neurological disorder and variants the non-coding gene RNU4-2.

Overall there is sufficient evidence to promote this gene to Green status at the next GMS panel update.; to: Comment on list classification: Multiple individuals have been identified in PMID: 38821540 with a clinically overlapping neurological disorder and variants the non-coding gene RNU4-2. Additional cases with mutual findings have also been reported in PMID: 38645094, corroborating this gene-disease association - however, PMID: 38645094 is still in preprint at this time.

Overall there is sufficient evidence to promote this gene to Green status at the next GMS panel update.
Severe microcephaly v5.15 RNU4-2 Arina Puzriakova changed review comment from: Comment on list classification: The two papers (PMID: 38821540; 38645094) corroborate mutual findings and report over 100 unrelated individuals with a clinically overlapping neurological disorder and variants the non-coding gene RNU4-2.

Overall there is sufficient evidence to promote this gene to Green status at the next GMS panel update.; to: Comment on list classification: Multiple individuals have been identified in PMID: 38821540 with a clinically overlapping neurological disorder and variants the non-coding gene RNU4-2. Additional cases with mutual findings have also been reported in PMID: 38645094, corroborating this gene-disease association - however, PMID: 38645094 is still in preprint at this time.

Overall there is sufficient evidence to promote this gene to Green status at the next GMS panel update.
Intellectual disability v6.50 RNU4-2 Arina Puzriakova changed review comment from: Second paper by Greene et al. 2024 (PMID: 38821540) reported on 73 unrelated cases with a neurodevelopmental disorder associated with heterozygous variants in the RNU4-2 gene, overlapping findings with the PMID: 38645094 paper (still currently in preprint). Participants were identified through their enrolment in various cohorts including the 100,000 Genomes Project, NHSE Genomic Medicine Service (GMS), and NIHR BioResource.

Almost all variants were acquired de novo, with the exception of one variant that was inherited from an affected mother and 16 probands with unknown inheritance due to lack of parental genotype data.
Variants cluster in two regions of RNU4-2 (n.62–70 and n.73–79) but the majority of cases harboured a recurrent variant, n.64_65insT.

Clinical presentation was predominantly characterised by intellectual disability, but other observed features include microcephaly, proportionate short stature, hypotonia, seizures and motor delay.; to: Greene et al. 2024 (PMID: 38821540) reported on 73 unrelated cases with a neurodevelopmental disorder associated with heterozygous variants in the RNU4-2 gene, overlapping findings in PMID:38645094 (still currently in preprint). Participants were identified through their enrolment in various cohorts including the 100,000 Genomes Project, NHSE Genomic Medicine Service (GMS), and NIHR BioResource.

Almost all variants were acquired de novo, with the exception of one variant that was inherited from an affected mother and 16 probands with unknown inheritance due to lack of parental genotype data.
Variants cluster in two regions of RNU4-2 (n.62–70 and n.73–79) but the majority of cases harboured a recurrent variant, n.64_65insT.

Clinical presentation was predominantly characterised by intellectual disability, but other observed features include microcephaly, proportionate short stature, hypotonia, seizures and motor delay.
Early onset or syndromic epilepsy v5.20 RNU4-2 Arina Puzriakova changed review comment from: Second paper by Greene et al. 2024 (PMID: 38821540) reported on 73 unrelated cases with a neurodevelopmental disorder associated with heterozygous variants in the RNU4-2 gene, overlapping findings with the PMID: 38645094 paper (still currently in preprint). Participants were identified through their enrolment in various cohorts including the 100,000 Genomes Project, NHSE Genomic Medicine Service (GMS), and NIHR BioResource.

Almost all variants were acquired de novo, with the exception of one variant that was inherited from an affected mother and 16 probands with unknown inheritance due to lack of parental genotype data.
Variants cluster in two regions of RNU4-2 (n.62–70 and n.73–79) but the majority of cases harboured a recurrent variant, n.64_65insT.

Clinical presentation was predominantly characterised by intellectual disability, but other observed features include microcephaly, proportionate short stature, hypotonia, seizures and motor delay.; to: Greene et al. 2024 (PMID: 38821540) reported on 73 unrelated cases with a neurodevelopmental disorder associated with heterozygous variants in the RNU4-2 gene, overlapping findings in PMID:38645094 (still currently in preprint). Participants were identified through their enrolment in various cohorts including the 100,000 Genomes Project, NHSE Genomic Medicine Service (GMS), and NIHR BioResource.

Almost all variants were acquired de novo, with the exception of one variant that was inherited from an affected mother and 16 probands with unknown inheritance due to lack of parental genotype data.
Variants cluster in two regions of RNU4-2 (n.62–70 and n.73–79) but the majority of cases harboured a recurrent variant, n.64_65insT.

Clinical presentation was predominantly characterised by intellectual disability, but other observed features include microcephaly, proportionate short stature, hypotonia, seizures and motor delay.
Severe microcephaly v5.15 RNU4-2 Arina Puzriakova changed review comment from: Second paper by Greene et al. 2024 (PMID: 38821540) reported on 73 unrelated cases with a neurodevelopmental disorder associated with heterozygous variants in the RNU4-2 gene, overlapping findings with the PMID: 38645094 paper (still currently in preprint). Participants were identified through their enrolment in various cohorts including the 100,000 Genomes Project, NHSE Genomic Medicine Service (GMS), and NIHR BioResource.

Almost all variants were acquired de novo, with the exception of one variant that was inherited from an affected mother and 16 probands with unknown inheritance due to lack of parental genotype data.
Variants cluster in two regions of RNU4-2 (n.62–70 and n.73–79) but the majority of cases harboured a recurrent variant, n.64_65insT.

Clinical presentation was predominantly characterised by intellectual disability, but other observed features include microcephaly, proportionate short stature, hypotonia, seizures and motor delay.; to: Greene et al. 2024 (PMID: 38821540) reported on 73 unrelated cases with a neurodevelopmental disorder associated with heterozygous variants in the RNU4-2 gene, overlapping findings in PMID:38645094 (still currently in preprint). Participants were identified through their enrolment in various cohorts including the 100,000 Genomes Project, NHSE Genomic Medicine Service (GMS), and NIHR BioResource.

Almost all variants were acquired de novo, with the exception of one variant that was inherited from an affected mother and 16 probands with unknown inheritance due to lack of parental genotype data.
Variants cluster in two regions of RNU4-2 (n.62–70 and n.73–79) but the majority of cases harboured a recurrent variant, n.64_65insT.

Clinical presentation was predominantly characterised by intellectual disability, but other observed features include microcephaly, proportionate short stature, hypotonia, seizures and motor delay.
Retinal disorders v5.15 AHR Mohammed Derar changed review comment from: Additional unrelated families with foveal hypoplasia have been reported with biallelic mutations in AHR. The mutations detected were homozygous nonesense variants in two different patients and a splicing variant in another patient.; to: Additional unrelated families with foveal hypoplasia have been reported with biallelic mutations in AHR. The mutations detected were homozygous nonesense variants in two different patients and a splicing variant in another patient.
Retinal disorders v5.15 DCT Mohammed Derar gene: DCT was added
gene: DCT was added to Retinal disorders. Sources: Literature
Mode of inheritance for gene: DCT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DCT were set to (Pennamen et al., 2021) (PMID: 33100333); (Volk et al., 2021) (PMID: 33959807)
Phenotypes for gene: DCT were set to oculocutaneous albinism; foveal hypoplasia; chiasmal misrouting; iris transillumination defect; nystagmus; ocular hypopigmentation
Penetrance for gene: DCT were set to Complete
Review for gene: DCT was set to GREEN
Added comment: Biallelic variants in DCT are reported to cause oculocutaneous albinism type 8 in multiple unrelated and affected families. This form of albinism has subtle hypopigmentation and displays the classical ocular manifestations of foveal hypoplasia, iris transillumination defect and fundus hypopigmentation. It is therefore imperative to sprobe DCT in patients with retinal abnormalities and presumbly normal pigmentation.
Sources: Literature
Retinal disorders v5.15 SLC38A8 Mohammed Derar changed review comment from: Biallelic variants in SLC38A8 cause isolated foveal hypoplasia, chisamal misrouting in the absence of pigmentation defects. The variable phenotype being anterior segment dysgenesis (Poulter et al., 2013). Bare in mind chiasmal misrouting is not always reported due to lack of access to the visual evoked potentials (VEP) test, technical difficulty in performing the test on infants and inconsistent results during childhood (Campbell et al., 2019). The differential feature of SLC38A8 is the absence of pigmentation defects however assessing pigmentation status proves challenging especially in fair populations thus some genuine SLC38A8 cases are misdiagnosed as albinism (Campbell et al., 2019). Oculomotor defects such as nystagmus accompanies foveal hypoplasia in its syndromic and isolated forms.; to: Biallelic variants in SLC38A8 cause isolated foveal hypoplasia, chisamal misrouting in the absence of pigmentation defects. The variable phenotype being anterior segment dysgenesis (Poulter et al., 2013). Bare in mind chiasmal misrouting is not always reported due to lack of access to the visual evoked potentials (VEP) test, technical difficulty in performing the test on infants and inconsistent results during childhood (Campbell et al., 2019). The differential feature of SLC38A8 is the absence of pigmentation defects however assessing pigmentation status proves challenging especially in fair populations thus some genuine SLC38A8 cases are misdiagnosed as albinism (Campbell et al., 2019). Oculomotor defects such as nystagmus accompanies isolated foveal hypoplasia.
Retinal disorders v5.15 AHR Mohammed Derar changed review comment from: additional unrelated families with foveal hypoplasia have been reported with biallelic mutations in AHR. The mutations detected were homozygous nonesense variants in two different patients and a splicing variant in another patient.; to: Additional unrelated families with foveal hypoplasia have been reported with biallelic mutations in AHR. The mutations detected were homozygous nonesense variants in two different patients and a splicing variant in another patient.
Retinal disorders v5.15 AHR Mohammed Derar changed review comment from: Unrelated families with foveal hypoplasia have been reported with biallelic mutations in AHR. The mutations detected were homozygous nonesense variants in two different patients and a splicing variant in another patient.; to: additional unrelated families with foveal hypoplasia have been reported with biallelic mutations in AHR. The mutations detected were homozygous nonesense variants in two different patients and a splicing variant in another patient.
Retinal disorders v5.15 FRMD7 Mohammed Derar edited their review of gene: FRMD7: Added comment: Further evidence from a study studing 904 patients with foveal hypoplasia detected FRMD7 variants in 3.5% of the cohort. The phenotype associated with FRMD7 mutations was a grade 1 foveal hypoplasia.; Changed publications to: (Choi et al., 2018) (PMID: 30025138), (Thomas et al., 2014) (PMID:24688117), (Kuht et al., 2022) (PMID:35157951)
Retinal disorders v5.15 FRMD7 Mohammed Derar changed review comment from: Mutations in FRMD7 are known to cause infantile nystagmus in an X-linked inheritance (Choi et al., 2018). Recently, with the aid of spectral domain OCT, patients with missense, splice site and nonsense variants in FRMD7 showed a shallow foveal pit diagnosed as grade 1foveal hypoplasia (Thomas et al., 2014)
Sources: Literature; to: Mutations in FRMD7 are known to cause infantile nystagmus in an X-linked inheritance (Choi et al., 2018). Recently, with the aid of spectral domain OCT, patients with missense, splice site and nonsense variants in FRMD7 showed a shallow foveal pit diagnosed as grade 1foveal hypoplasia (Thomas et al., 2014)
Sources: Literature
Retinal disorders v5.15 PAX6 Mohammed Derar changed review comment from: Additional evidence from multiple families with isolated foveal hypoplasia (without aniridia) and monoallelic variants in PAX6.; to: Additional evidence from multiple families with isolated foveal hypoplasia (without aniridia) having monoallelic variants in PAX6.
Respiratory ciliopathies including non-CF bronchiectasis v3.11 DAW1 Achchuthan Shanmugasundram Tag Q4_22_MOI was removed from gene: DAW1.
Laterality disorders and isomerism v3.15 DAW1 Achchuthan Shanmugasundram Tag Q4_22_MOI was removed from gene: DAW1.
Paroxysmal central nervous system disorders v3.10 RHOBTB2 Achchuthan Shanmugasundram Tag Q3_23_MOI was removed from gene: RHOBTB2.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.34 SMCHD1 Achchuthan Shanmugasundram Mode of inheritance for gene: SMCHD1 was changed from Other - please specifiy in evaluation comments to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.33 SMCHD1 Achchuthan Shanmugasundram Tag Q1_24_MOI was removed from gene: SMCHD1.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.33 HMGCR Achchuthan Shanmugasundram Tag Q3_23_MOI was removed from gene: HMGCR.
Optic neuropathy v4.30 LETM1 Achchuthan Shanmugasundram Tag Q3_23_MOI was removed from gene: LETM1.
Possible mitochondrial disorder - nuclear genes v3.106 LETM1 Achchuthan Shanmugasundram Tag Q3_23_MOI was removed from gene: LETM1.
Familial hypoparathyroidism v2.15 STX16 Achchuthan Shanmugasundram Tag Q4_22_MOI was removed from gene: STX16.
Monogenic hearing loss v4.50 LETM1 Achchuthan Shanmugasundram Tag Q3_23_MOI was removed from gene: LETM1.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.10 IL6ST Achchuthan Shanmugasundram changed review comment from: Comment on mode of inheritance: As reviewed previously by Zornitza Stark, MOI of this gene should be updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' in the next GMS update.; to: Comment on mode of inheritance: As reviewed previously by Zornitza Stark, there is sufficient evidence available for the association of monoallelic IL6ST variants to this panel. Hence, the MOI should be updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' in the next GMS update.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.10 IL6ST Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: As reviewed previously by Zornitza Stark, MOI of this gene should be updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' in the next GMS update.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.10 IL6ST Achchuthan Shanmugasundram Mode of inheritance for gene: IL6ST was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.9 IL6ST Achchuthan Shanmugasundram Phenotypes for gene: IL6ST were changed from Hyper-IgE recurrent infection syndrome 4, autosomal recessive 618523; Stuve-Wiedemann-like syndrome: skeletal dysplasia, neonatal lung dysfunction, thrombocytopenia, dermatitis, defective acute-phase response.; Hyper-IgE syndrome, autosomal dominant to Hyper-IgE syndrome 4A, autosomal dominant, with recurrent infections, OMIM:619752; ?Immunodeficiency 94 with autoinflammation and dysmorphic facies, OMIM:619750; Hyper-IgE syndrome 4B, autosomal recessive, with recurrent infections, OMIM:618523; Stuve-Wiedemann syndrome 2, OMIM:619751
Primary immunodeficiency or monogenic inflammatory bowel disease v5.8 IL6ST Achchuthan Shanmugasundram Tag Q3_24_MOI tag was added to gene: IL6ST.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.8 IL6ST Achchuthan Shanmugasundram reviewed gene: IL6ST: Rating: GREEN; Mode of pathogenicity: Other; Publications: 32207811; Phenotypes: Hyper-IgE syndrome 4A, autosomal dominant, with recurrent infections, OMIM:619752, ?Immunodeficiency 94 with autoinflammation and dysmorphic facies, OMIM:619750, Hyper-IgE syndrome 4B, autosomal recessive, with recurrent infections, OMIM:618523, Stuve-Wiedemann syndrome 2, OMIM:619751; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Retinal disorders v5.15 PAX6 Mohammed Derar edited their review of gene: PAX6: Added comment: Additional evidence from multiple families with isolated foveal hypoplasia (without aniridia) and monoallelic variants in PAX6.; Changed publications to: (Hingorani et al., 2009) (PMID: 19218613), (Thomas et al., 2014) (PMID: 23942204), (Cunha et al., 2021) (PMID: 33024313), (Jiang et al., 2021) (PMID:34415986), (Azuma et al., 1996) (https://doi.org/10.1086/302529)
Retinal disorders v5.15 AHR Mohammed Derar edited their review of gene: AHR: Added comment: Unrelated families with foveal hypoplasia have been reported with biallelic mutations in AHR. The mutations detected were homozygous nonesense variants in two different patients and a splicing variant in another patient.; Changed publications to: (Mayer et al., 2019) (PMID: 31009037), (Borovok et al., 2020) (PMID: 33193710), (AlMoallem et al., 2022) (PMID:35188035)
Amyotrophic lateral sclerosis/motor neuron disease v1.69 UNC13A David Collier reviewed gene: UNC13A: Rating: AMBER; Mode of pathogenicity: None; Publications: PubMed: 32627229, PMID: 19734901, PMID: 35197628, PMID: 30739198, PMID: 24931836; Phenotypes: ALS, amyotrophic lateral sclerosis, motor neuron disease, MND, Frontotemporal Dementia (FTD), ALS and FTD (FTD-TDP); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Amyotrophic lateral sclerosis/motor neuron disease v1.69 ANXA11 David Collier reviewed gene: ANXA11: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 28469040, PMID: 30337194, PubMed: 34048612; Phenotypes: ALS, amyotrophic lateral sclerosis, ALS 23, motor neuron disease, Inclusion body myopathy and brain white matter abnormalities (IBMWMA, MULTISYSTEM PROTEINOPATHY 6, MSP6); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare genetic inflammatory skin disorders v3.20 RNU12 Arina Puzriakova Phenotypes for gene: RNU12 were changed from porokeratosis; erythematous cutaneous eruption to CDAGS syndrome, OMIM:603116; porokeratosis; erythematous cutaneous eruption
Rare genetic inflammatory skin disorders v3.19 RNU12 Arina Puzriakova Tag gene-checked was removed from gene: RNU12.
Rare syndromic craniosynostosis or isolated multisuture synostosis v5.1 RNU12 Arina Puzriakova Tag gene-checked was removed from gene: RNU12.
Amyotrophic lateral sclerosis/motor neuron disease v1.69 SPG11 David Collier reviewed gene: SPG11: Rating: GREEN; Mode of pathogenicity: None; Publications: PubMed: 20110243, PMID: 36445564, PMID: 37133535, PMID: 27066562, PMID: 25681989, PMID: 38938072; Phenotypes: Juvenile amyotrophic lateral sclerosis (ALS) with long survival, hereditary motor sensory neuropathy (Charcot–Marie–Tooth disease type 2X), and multiple sclerosis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rare syndromic craniosynostosis or isolated multisuture synostosis v5.1 RNU12 Arina Puzriakova commented on gene: RNU12: This gene has been tagged again for promotion from Amber to Green as there is enough evidence to support a gene-disease association. RNU12 was not previously added as it is a non-coding gene that was not tiered but it has since been added to the tiering pipeline. Therefore it is appropriate to upgrade it to Green status.
Rare genetic inflammatory skin disorders v3.19 RNU12 Arina Puzriakova Tag locus-type-rna-small-nuclear tag was added to gene: RNU12.
Rare syndromic craniosynostosis or isolated multisuture synostosis v5.1 RNU12 Arina Puzriakova Tag currently-ngs-unreportable was removed from gene: RNU12.
Tag Q3_24_promote_green tag was added to gene: RNU12.
Tag locus-type-rna-small-nuclear tag was added to gene: RNU12.
Rare genetic inflammatory skin disorders v3.19 RNU12 Arina Puzriakova commented on gene: RNU12: Removed 'currently-ngs-unreportable' tag as tiering of non-coding genes including RNU12, has now been added to the Genomics England Rare Disease pipeline. The Ensembl ID for RNU12 has also been added.
Rare genetic inflammatory skin disorders v3.19 RNU12 Arina Puzriakova Tag currently-ngs-unreportable was removed from gene: RNU12.
Rare syndromic craniosynostosis or isolated multisuture synostosis v5.1 RNU12 Arina Puzriakova commented on gene: RNU12
Amyotrophic lateral sclerosis/motor neuron disease v1.69 SQSTM1 David Collier reviewed gene: SQSTM1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 22084127 PMID: 23417734 PMID: 23303844 PMID: 22972638 PMID: 24138988 PMID: 24042580 PMID: 23942205, PMID: 23812289, PMID: 25700176, PMID: 28889094, PMID: 29457785, PMID: 31859009, PMID: 32028661; Phenotypes: ALS, MND, motor neuron disease, Amyotrophic Lateral Sclerosis, Amyotrophic Lateral Sclerosis 3, Paget's disease of bone, frontotemporal lobar degeneration, Childhood-Onset Neurodegeneration with Ataxia, Dystonia, and Gaze Palsy, Myopathy, distal, with rimmed vacuoles; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
White matter disorders and cerebral calcification - narrow panel v4.4 NAA60 Sarah Leigh Phenotypes for gene: NAA60 were changed from NAA60 associated autosomal recessive primary familial brain calcifications to Basal ganglia calcification, idiopathic, 9, autosomal recessive, OMIM:620786; basal ganglia calcification, idiopathic, 9, autosomal recessive, MONDO:0968977
Hereditary ataxia with onset in adulthood v5.4 NAA60 Sarah Leigh Phenotypes for gene: NAA60 were changed from NAA60 associated autosomal recessive primary familial brain calcifications to Basal ganglia calcification, idiopathic, 9, autosomal recessive, OMIM:620786; basal ganglia calcification, idiopathic, 9, autosomal recessive, MONDO:0968977
Adult onset neurodegenerative disorder v5.8 NAA60 Sarah Leigh Phenotypes for gene: NAA60 were changed from NAA60 associated autosomal recessive primary familial brain calcifications to Basal ganglia calcification, idiopathic, 9, autosomal recessive, OMIM:620786; basal ganglia calcification, idiopathic, 9, autosomal recessive, MONDO:0968977
Adult onset neurodegenerative disorder v5.7 NAA60 Sarah Leigh Tag Q2_24_MOI was removed from gene: NAA60.
White matter disorders and cerebral calcification - narrow panel v4.3 NAA60 Sarah Leigh Tag Q2_24_MOI was removed from gene: NAA60.
Hereditary ataxia with onset in adulthood v5.3 NAA60 Sarah Leigh Tag Q2_24_MOI was removed from gene: NAA60.
Hereditary ataxia with onset in adulthood v5.3 NAA60 Sarah Leigh edited their review of gene: NAA60: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v4.3 NAA60 Sarah Leigh edited their review of gene: NAA60: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.8 IL1R1 Achchuthan Shanmugasundram Classified gene: IL1R1 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.8 IL1R1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Dmitrijs Rots, PMID:37315560 reported the identification of monoallelic IL1R1 variant (p.Lys131Glu) in a patient with chronic recurrent multifocal osteomyelitis and some functional evidence in support of the association.

Hence, this gene can be rated amber with the current evidence.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.8 IL1R1 Achchuthan Shanmugasundram Gene: il1r1 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v5.7 IL1R1 Achchuthan Shanmugasundram Phenotypes for gene: IL1R1 were changed from chronic recurrent multifocal osteomyelitis to ?Chronic recurrent multifocal osteomyelitis 3, OMIM:259680
Primary immunodeficiency or monogenic inflammatory bowel disease v5.6 IL1R1 Achchuthan Shanmugasundram Publications for gene: IL1R1 were set to PMID: 37315560
Primary immunodeficiency or monogenic inflammatory bowel disease v5.5 IL1R1 Achchuthan Shanmugasundram edited their review of gene: IL1R1: Changed rating: AMBER
Primary immunodeficiency or monogenic inflammatory bowel disease v5.5 IL1R1 Achchuthan Shanmugasundram reviewed gene: IL1R1: Rating: RED; Mode of pathogenicity: None; Publications: 37315560; Phenotypes: ?Chronic recurrent multifocal osteomyelitis 3, OMIM:259680; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.50 DIP2B Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v6.50 DIP2B Achchuthan Shanmugasundram Classified gene: DIP2B as Red List (low evidence)
Intellectual disability v6.50 DIP2B Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by others, only STRs in DIP2B were previously associated with intellectual disability. Hence, the rating should be changed from amber to red and the STR should be added to this panel.
Intellectual disability v6.50 DIP2B Achchuthan Shanmugasundram Gene: dip2b has been classified as Red List (Low Evidence).
Intellectual disability v6.50 DIP2B Achchuthan Shanmugasundram Classified gene: DIP2B as Red List (low evidence)
Intellectual disability v6.50 DIP2B Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by others, only STRs in DIP2B were previously associated with intellectual disability. Hence, the rating should be changed from amber to red and the STR should be added to this panel.
Intellectual disability v6.50 DIP2B Achchuthan Shanmugasundram Gene: dip2b has been classified as Red List (Low Evidence).
Fetal anomalies v4.23 ESAM Achchuthan Shanmugasundram Tag Q4_23_expert_review was removed from gene: ESAM.
Tag Q4_23_NHS_review tag was added to gene: ESAM.
Adult onset neurodegenerative disorder v5.7 NAA60 Sarah Leigh edited their review of gene: NAA60: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cystic kidney disease v5.8 COL4A3 John Sayer changed review comment from: evidence pointing for CDOL4A3/4/5 causing mild cystic phenotypes
Sources: Research; to: evidence pointing for COL4A3/4/5 causing mild cystic phenotypes
Sources: Research
Cystic kidney disease v5.8 COL4A3 John Sayer gene: COL4A3 was added
gene: COL4A3 was added to Cystic kidney disease. Sources: Research
Mode of inheritance for gene: COL4A3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COL4A3 were set to 38178635; 35602506
Phenotypes for gene: COL4A3 were set to cystic kidney disease; proteinuria; haematuria
Penetrance for gene: COL4A3 were set to Incomplete
Review for gene: COL4A3 was set to RED
Added comment: evidence pointing for CDOL4A3/4/5 causing mild cystic phenotypes
Sources: Research
Cystic kidney disease v5.8 COL4A4 John Sayer changed review comment from: may phenocopy PKD1
Sources: Other; to: may phenocopy PKD1
Sources: Other


additional new publication
PMID: 38178635
Cystic kidney disease v5.8 COL4A5 John Sayer commented on gene: COL4A5: Additional publication supporting this gene with cystic kidney phenotypes
PMID: 38680391
Intellectual disability v6.49 HSD17B10 Achchuthan Shanmugasundram Deleted their review
Intellectual disability v6.49 HSD17B10 Achchuthan Shanmugasundram reviewed gene: HSD17B10: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Unexplained young onset end-stage renal disease - additional genes v0.0 Achchuthan Shanmugasundram Added Panel Unexplained young onset end-stage renal disease - additional genes
Set panel types to: GMS Rare Disease Virtual; GMS Rare Disease; Component Of Super Panel
Pulmonary arterial hypertension v3.6 SARS2 Achchuthan Shanmugasundram Mode of inheritance for gene: SARS2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v4.23 MED12 Achchuthan Shanmugasundram Deleted their review
Fetal anomalies v4.23 MED12 Achchuthan Shanmugasundram reviewed gene: MED12: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Retinal disorders v5.15 CLEC3B Dmitrijs Rots gene: CLEC3B was added
gene: CLEC3B was added to Retinal disorders. Sources: Literature
Mode of inheritance for gene: CLEC3B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CLEC3B were set to PMID: 35331648
Phenotypes for gene: CLEC3B were set to Macular dystrophy, retinal, 4
Review for gene: CLEC3B was set to GREEN
Added comment: The study described: "5 multigenerational families diagnosed with autosomal dominant maculoretinopathy were found to carry a pathogenic variant in a new gene, CLEC3B, which encodes tetranectin, a plasminogen kringle-4 binding protein. Consistent with the disease phenotypes of patients, mice that received subretinal injections with the CLEC3B variant displayed multiple subretinal hyperreflective deposits, reduced retinal thickness, and decreased electroretinographic responses. Moreover, the optokinetic tracking response indicated that spatial frequency was significantly lower (P < .05), implying impaired visual function in these mice."
Sources: Literature
Intellectual disability v6.49 FEM1B Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As recently reviewed by Zornitza Stark, five unrelated individuals are reported with a syndromic neurodevelopmental disorder and identified with the same missense variant p.Arg126Gln. All five individuals presented with global developmental delay and all four patients tested for intellectual disability had ID.

This gene has not yet been associated with any phenotypes either in OMIM or in Gene2Phenotype.

Although only one variant was reported, there is functional evidence available for this variant. Hence, this gene can be promoted to green rating in the next GMS update.; to: Comment on list classification: As recently reviewed by Zornitza Stark, five unrelated individuals were reported with a syndromic neurodevelopmental disorder and identified with the same missense variant p.Arg126Gln. All five individuals presented with global developmental delay and all four patients tested for intellectual disability had ID.

This gene has not yet been associated with any phenotypes either in OMIM or in Gene2Phenotype.

Although only one variant was reported, there is functional evidence available for this variant. Hence, this gene can be promoted to green rating in the next GMS update.
Intellectual disability v6.49 FEM1B Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As recently reviewed by Zornitza Stark, five unrelated individuals are reported with a syndromic neurodevelopmental disorder and identified with the same missense variant p.Arg126Gln.

Although only one variant was reported, there is functional evidence available for this variant. Hence, this gene can be promoted to green rating in the next GMS update.; to: Comment on list classification: As recently reviewed by Zornitza Stark, five unrelated individuals are reported with a syndromic neurodevelopmental disorder and identified with the same missense variant p.Arg126Gln. All five individuals presented with global developmental delay and all four patients tested for intellectual disability had ID.

This gene has not yet been associated with any phenotypes either in OMIM or in Gene2Phenotype.

Although only one variant was reported, there is functional evidence available for this variant. Hence, this gene can be promoted to green rating in the next GMS update.
Intellectual disability v6.49 FEM1B Achchuthan Shanmugasundram Classified gene: FEM1B as Amber List (moderate evidence)
Intellectual disability v6.49 FEM1B Achchuthan Shanmugasundram Added comment: Comment on list classification: As recently reviewed by Zornitza Stark, five unrelated individuals are reported with a syndromic neurodevelopmental disorder and identified with the same missense variant p.Arg126Gln.

Although only one variant was reported, there is functional evidence available for this variant. Hence, this gene can be promoted to green rating in the next GMS update.
Intellectual disability v6.49 FEM1B Achchuthan Shanmugasundram Gene: fem1b has been classified as Amber List (Moderate Evidence).
Intellectual disability v6.48 FEM1B Achchuthan Shanmugasundram Phenotypes for gene: FEM1B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v6.48 FEM1B Achchuthan Shanmugasundram Phenotypes for gene: FEM1B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v6.48 FEM1B Achchuthan Shanmugasundram Phenotypes for gene: FEM1B were changed from Syndromic intellectual disability to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v6.48 FEM1B Achchuthan Shanmugasundram Publications for gene: FEM1B were set to 31036916; 38465576
Intellectual disability v6.48 FEM1B Achchuthan Shanmugasundram Publications for gene: FEM1B were set to 31036916; 38465576
Intellectual disability v6.48 FEM1B Achchuthan Shanmugasundram Publications for gene: FEM1B were set to 31036916
Intellectual disability v6.47 FEM1B Achchuthan Shanmugasundram Mode of inheritance for gene: FEM1B was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.47 FEM1B Achchuthan Shanmugasundram Mode of inheritance for gene: FEM1B was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.46 FEM1B Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: FEM1B.
Intellectual disability v6.46 FEM1B Achchuthan Shanmugasundram edited their review of gene: FEM1B: Changed rating: GREEN
Intellectual disability v6.46 FEM1B Achchuthan Shanmugasundram reviewed gene: FEM1B: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Amelogenesis imperfecta v3.9 AMBN Achchuthan Shanmugasundram Tag Q2_24_MOI tag was added to gene: AMBN.
Amelogenesis imperfecta v3.9 AMBN Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There is sufficient evidence available for the association of both monoallelic and biallelic AMBN variants with amelogenesis imperfecta. However, only the autosomal recessive phenotype has been reported in OMIM.

The MOI should be updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' in the next GMS update.
Amelogenesis imperfecta v3.9 AMBN Achchuthan Shanmugasundram Mode of inheritance for gene: AMBN was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Amelogenesis imperfecta v3.8 AMBN Achchuthan Shanmugasundram Phenotypes for gene: AMBN were changed from Amelogenesis imperfecta, type IF, 616270 to Amelogenesis imperfecta, type IF, OMIM:616270
Amelogenesis imperfecta v3.7 AMBN Achchuthan Shanmugasundram Publications for gene: AMBN were set to 24858907; 26502894
Amelogenesis imperfecta v3.6 AMBN Achchuthan Shanmugasundram reviewed gene: AMBN: Rating: GREEN; Mode of pathogenicity: None; Publications: 30174330, 31402633, 38058155; Phenotypes: Amelogenesis imperfecta, type IF, OMIM:616270; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.5 NUDCD3 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: Although all four unrelated families had the same variant, there is functional evidence available for the variant. Hence, this gene can be promoted to green rating in the next GMS update.; to: Comment on list classification: Although all four unrelated families harboured the same variant, there is functional evidence available for this variant. Hence, this gene can be promoted to green rating in the next GMS update.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.5 NUDCD3 Achchuthan Shanmugasundram Classified gene: NUDCD3 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.5 NUDCD3 Achchuthan Shanmugasundram Added comment: Comment on list classification: Although all four unrelated families had the same variant, there is functional evidence available for the variant. Hence, this gene can be promoted to green rating in the next GMS update.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.5 NUDCD3 Achchuthan Shanmugasundram Gene: nudcd3 has been classified as Amber List (Moderate Evidence).
Adult onset neurodegenerative disorder v5.7 RAB32 Dmitrijs Rots gene: RAB32 was added
gene: RAB32 was added to Adult onset neurodegenerative disorder. Sources: Literature
Mode of inheritance for gene: RAB32 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAB32 were set to PMID: 38858457
Phenotypes for gene: RAB32 were set to Parkinson’s disease
Mode of pathogenicity for gene: RAB32 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: RAB32 was set to GREEN
Added comment: The PMID: 38858457 paper describes: "Exome-wide analyses converged on RAB32 as a novel PD gene identifying c.213C > G/p.S71R as a high-risk variant presenting in ~0.7% of familial PD cases while observed in only 0.004% of controls (odds ratio of 65.5). This variant was confirmed in all cases via Sanger sequencing and segregated with PD in three families." + functional data. Enough evidence for the green rating.
Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v5.4 NUDCD3 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: NUDCD3.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.4 NUDCD3 Achchuthan Shanmugasundram gene: NUDCD3 was added
gene: NUDCD3 was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: NUDCD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUDCD3 were set to 38787962
Phenotypes for gene: NUDCD3 were set to severe combined immunodeficiency, MONDO:0015974; Omenn syndrome, MONDO:0011338
Review for gene: NUDCD3 was set to GREEN
Added comment: PMID:38787962 reported 11 patients across four consanguineous kindreds with a single deleterious missense variant in NUDCD3 gene in homozygous state. Two infants had severe combined immunodeficiency with the complete absence of T and B cells), whereas nine showed classical features of Omenn syndrome.

Patient cells showed reduced expression of NUDCD3 protein and diminished ability to support RAG-mediated recombination in vitro. Although impaired V(D)J recombination in a mouse model bearing the homologous variant led to milder immunologic abnormalities, NUDCD3 is absolutely required for healthy T and B cell development in humans.

This gene has not yet been associated with any phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Monogenic hearing loss v4.50 PKHD1L1 Achchuthan Shanmugasundram Classified gene: PKHD1L1 as Amber List (moderate evidence)
Monogenic hearing loss v4.50 PKHD1L1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Barbara Vona and reported in PMID:38459354, there are four unrelated cases reported with biallelic PKHD1L1 variants and non-syndromic sensorineural hearing loss. In addition, there are data from mouse and zebrafish models available in support of the disease association.

This gene has been associated with relevant phenotype in OMIM (MIM #620794), but not yet in Gene2Phenotype.

Hence, this gene can be promoted to green rating in the next GMS update.
Monogenic hearing loss v4.50 PKHD1L1 Achchuthan Shanmugasundram Gene: pkhd1l1 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v4.49 PKHD1L1 Achchuthan Shanmugasundram Phenotypes for gene: PKHD1L1 were changed from Deafness, autosomal recessive 124, OMIM:620794 to Deafness, autosomal recessive 124, OMIM:620794
Monogenic hearing loss v4.49 PKHD1L1 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: PKHD1L1.
Monogenic hearing loss v4.49 PKHD1L1 Achchuthan Shanmugasundram Phenotypes for gene: PKHD1L1 were changed from Hearing loss to Deafness, autosomal recessive 124, OMIM:620794
Monogenic hearing loss v4.48 PKHD1L1 Achchuthan Shanmugasundram Publications for gene: PKHD1L1 were set to PMID: 38459354
Monogenic hearing loss v4.47 PKHD1L1 Achchuthan Shanmugasundram reviewed gene: PKHD1L1: Rating: GREEN; Mode of pathogenicity: None; Publications: 38459354; Phenotypes: Deafness, autosomal recessive 124, OMIM:620794; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.20 ADGRL1 Achchuthan Shanmugasundram Classified gene: ADGRL1 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v5.20 ADGRL1 Achchuthan Shanmugasundram Gene: adgrl1 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v5.20 ADGRL1 Achchuthan Shanmugasundram Classified gene: ADGRL1 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v5.20 ADGRL1 Achchuthan Shanmugasundram Gene: adgrl1 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v5.19 ADGRL1 Achchuthan Shanmugasundram gene: ADGRL1 was added
gene: ADGRL1 was added to Early onset or syndromic epilepsy. Sources: Literature
Mode of inheritance for gene: ADGRL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ADGRL1 were set to 35907405
Phenotypes for gene: ADGRL1 were set to Developmental delay, behavioral abnormalities, and neuropsychiatric disorders, OMIM:620065
Review for gene: ADGRL1 was set to AMBER
Added comment: PMID:35907405 reported the identification of monoallelic ADGRL1 variants in ten individuals with a neurodevelopmental disorder comprising developmental delay, intellectual disability, attention deficit hyperactivity and autism spectrum disorders, and epilepsy. This includes a case that was previously reported in PMID:30504930. Epilepsy was reported in two of these cases. This gene has been associated with relevant phenotype in OMIM (MIM #620065), but not yet in Gene2Phenotype.
Sources: Literature
Intellectual disability v6.46 ADGRL1 Achchuthan Shanmugasundram Classified gene: ADGRL1 as Amber List (moderate evidence)
Intellectual disability v6.46 ADGRL1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (five unrelated cases) for the promotion of this gene to green rating in the next GMS update.
Intellectual disability v6.46 ADGRL1 Achchuthan Shanmugasundram Gene: adgrl1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v6.45 ADGRL1 Achchuthan Shanmugasundram Publications for gene: ADGRL1 were set to 30504930; 35907405
Intellectual disability v6.45 ADGRL1 Achchuthan Shanmugasundram Publications for gene: ADGRL1 were set to 35907405
Pulmonary arterial hypertension v3.5 CAPNS1 Dmitrijs Rots gene: CAPNS1 was added
gene: CAPNS1 was added to Pulmonary arterial hypertension. Sources: Literature
Mode of inheritance for gene: CAPNS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAPNS1 were set to PMID:38230350
Phenotypes for gene: CAPNS1 were set to pulmonary arterial hypertension
Review for gene: CAPNS1 was set to GREEN
Added comment: PMID:38230350 describes two independent families with three affected individuals with homozygous variants segregating in the family with the phenotype + some functional evidence.
Sources: Literature
Intellectual disability v6.44 ADGRL1 Achchuthan Shanmugasundram edited their review of gene: ADGRL1: Added comment: PMID:35907405 reported the identification of monoallelic ADGRL1 variants in ten individuals with a neurodevelopmental disorder comprising developmental delay, intellectual disability, attention deficit hyperactivity and autism spectrum disorders, and epilepsy. This includes a case that was previously reported in PMID:30504930. Mild/ moderate intellectual disability was reported in five of these ten cases.

This gene has been associated with relevant phenotype in OMIM (MIM #620065), but not yet in Gene2Phenotype.; Changed publications to: 30504930, 35907405
Intellectual disability v6.44 ADGRL1 Achchuthan Shanmugasundram Phenotypes for gene: ADGRL1 were changed from Developmental delay, behavioral abnormalities, and neuropsychiatric disorders to Developmental delay, behavioral abnormalities, and neuropsychiatric disorders, OMIM:620065
Intellectual disability v6.43 ADGRL1 Achchuthan Shanmugasundram Publications for gene: ADGRL1 were set to PubMed: 35907405
Intellectual disability v6.42 ADGRL1 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: ADGRL1.
Intellectual disability v6.42 ADGRL1 Achchuthan Shanmugasundram reviewed gene: ADGRL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35907405; Phenotypes: Developmental delay, behavioral abnormalities, and neuropsychiatric disorders, OMIM:620065; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v5.18 KCNB2 Achchuthan Shanmugasundram Classified gene: KCNB2 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v5.18 KCNB2 Achchuthan Shanmugasundram Gene: kcnb2 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v5.18 KCNB2 Achchuthan Shanmugasundram Classified gene: KCNB2 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v5.18 KCNB2 Achchuthan Shanmugasundram Gene: kcnb2 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v5.17 KCNB2 Achchuthan Shanmugasundram gene: KCNB2 was added
gene: KCNB2 was added to Early onset or syndromic epilepsy. Sources: Literature
Mode of inheritance for gene: KCNB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNB2 were set to 38503299
Phenotypes for gene: KCNB2 were set to neurodevelopmental disorder, MONDO:0700092
Review for gene: KCNB2 was set to AMBER
Added comment: PMID:38503299 reported seven unrelated individuals with monoallelic KCNB2 variants and neurodevelopmental disorder, of which two of them had seizures.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability v6.42 KCNB2 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Zornitza Stark, PMID:38503299 reported seven unrelated individuals with monoallelic KCNB2 variants and neurodevelopmental disorder, of which six of them had intellectual disability.; to: Comment on list classification: As reviewed by Zornitza Stark, PMID:38503299 reported seven unrelated individuals with monoallelic KCNB2 variants and neurodevelopmental disorder, of which six of them had intellectual disability.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Intellectual disability v6.42 KCNB2 Achchuthan Shanmugasundram Classified gene: KCNB2 as Amber List (moderate evidence)
Intellectual disability v6.42 KCNB2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, PMID:38503299 reported seven unrelated individuals with monoallelic KCNB2 variants and neurodevelopmental disorder, of which six of them had intellectual disability.
Intellectual disability v6.42 KCNB2 Achchuthan Shanmugasundram Gene: kcnb2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v6.41 KCNB2 Achchuthan Shanmugasundram Phenotypes for gene: KCNB2 were changed from neurodevelopmental disorder MONDO:0700092, KCNB2-related to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v6.40 KCNB2 Achchuthan Shanmugasundram edited their review of gene: KCNB2: Changed phenotypes to: neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071
Intellectual disability v6.40 KCNB2 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: KCNB2.
Intellectual disability v6.40 KCNB2 Achchuthan Shanmugasundram reviewed gene: KCNB2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Severe microcephaly v5.15 SASS6 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: SASS6.
Severe microcephaly v5.15 SASS6 Achchuthan Shanmugasundram Classified gene: SASS6 as Amber List (moderate evidence)
Severe microcephaly v5.15 SASS6 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there are two additional unrelated cases reported with severe microcephaly (HC was beyond -4 SD in both cases). Hence, this gene can be promoted to green rating in the next GMS update.
Severe microcephaly v5.15 SASS6 Achchuthan Shanmugasundram Gene: sass6 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v5.14 SASS6 Achchuthan Shanmugasundram Publications for gene: SASS6 were set to 24951542; 30639237
Severe microcephaly v5.13 SASS6 Achchuthan Shanmugasundram Phenotypes for gene: SASS6 were changed from ?Microcephaly 14, primary, autosomal recessive, OMIM:616402 to Microcephaly 14, primary, autosomal recessive, OMIM:616402
Severe microcephaly v5.12 SASS6 Achchuthan Shanmugasundram reviewed gene: SASS6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Microcephaly 14, primary, autosomal recessive, OMIM:616402; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v4.47 GRXCR2 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Sadaf Naz, one family from Pakistan was reported with homozygous c.714dupT (p.Gly239TrpfsTer74) variant, and one family and an unrelated individual were reported with homozygous c.251delC (p.Ile85SerfsTer33) variant. In addition, some functional evidence is available for these variants.

Hence, this gene can be promoted to green rating in the next GMS update.; to: Comment on list classification: As reviewed by Sadaf Naz, one family from Pakistan was reported with homozygous c.714dupT (p.Gly239TrpfsTer74) variant, and one family and an unrelated individual from Cameroon were reported with homozygous c.251delC (p.Ile85SerfsTer33) variant. In addition, some functional evidence is available for these variants.

Hence, this gene can be promoted to green rating in the next GMS update.
Monogenic hearing loss v4.47 GRXCR2 Achchuthan Shanmugasundram Classified gene: GRXCR2 as Amber List (moderate evidence)
Monogenic hearing loss v4.47 GRXCR2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Sadaf Naz, one family from Pakistan was reported with homozygous c.714dupT (p.Gly239TrpfsTer74) variant, and one family and an unrelated individual were reported with homozygous c.251delC (p.Ile85SerfsTer33) variant. In addition, some functional evidence is available for these variants.

Hence, this gene can be promoted to green rating in the next GMS update.
Monogenic hearing loss v4.47 GRXCR2 Achchuthan Shanmugasundram Gene: grxcr2 has been classified as Amber List (Moderate Evidence).
Parkinson Disease and Complex Parkinsonism v1.121 ARSA David Collier gene: ARSA was added
gene: ARSA was added to Parkinson Disease and Complex Parkinsonism. Sources: Expert list
Mode of inheritance for gene: ARSA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARSA were set to PMID: 37381728 PMID: 31312839 PMID: 31312839
Penetrance for gene: ARSA were set to unknown
Review for gene: ARSA was set to AMBER
Added comment: Association bertween these gene and Parkinson's has been controversial, however a recent publication adds to the supportive evidence for this gene (PMID: 37381728). Gene for Metachromatic leukodystrophy (MIM 250100 AR)
Sources: Expert list
Monogenic hearing loss v4.46 GRXCR2 Achchuthan Shanmugasundram Publications for gene: GRXCR2 were set to
Monogenic hearing loss v4.45 GRXCR2 Achchuthan Shanmugasundram Phenotypes for gene: GRXCR2 were changed from ?Deafness, autosomal recessive 101, 615837 to ?Deafness, autosomal recessive 101, OMIM:615837
Monogenic hearing loss v4.44 GRXCR2 Achchuthan Shanmugasundram Mode of inheritance for gene: GRXCR2 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v4.44 GRXCR2 Achchuthan Shanmugasundram Mode of inheritance for gene: GRXCR2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v4.43 GRXCR2 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: GRXCR2.
Monogenic hearing loss v4.43 GRXCR2 Achchuthan Shanmugasundram reviewed gene: GRXCR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24619944, 33528103; Phenotypes: ?Deafness, autosomal recessive 101, OMIM:615837; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Parkinson Disease and Complex Parkinsonism v1.121 SYNJ1 David Collier reviewed gene: SYNJ1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38853950 PMID: 36148638 PubMed: 23804563 PMID: 33841314 PubMed: 23804577 PubMed; Phenotypes: Early onset parkinsonism, Developmental and epileptic encephalopathy, Dystonia-parkinsonism accompanied by a frontal syndrome and oculomotor disturbances, Tonic-clonic seizures during childhood, severe intellectual disability, progressive parkinsonism; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Parkinson Disease and Complex Parkinsonism v1.121 VPS13C David Collier reviewed gene: VPS13C: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34875562 PMID: 33579389 PMID: 33039764 PMID: 30452786 PMID: 28862745 PMID: 28137300 PMID: 26942284; Phenotypes: Dementia with Lewy bodies, Early-onset autosomal recessive Parkinson's disease, Early onset Parkinsonism; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Parkinson Disease and Complex Parkinsonism v1.121 ATP13A2 David Collier reviewed gene: ATP13A2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 16964263 PMID: 17485642 PMID: 20310007; Phenotypes: Kufor-Rakeb syndrome, spastic paraplegia-78 (SPG78), juvenile-onset atypical Parkinson disease, supranuclear gaze palsy, spasticity, dementia, spastic paraplegia, brain iron accumulation; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cystic kidney disease v5.8 OFD1 Achchuthan Shanmugasundram edited their review of gene: OFD1: Changed rating: AMBER; 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)
Cystic kidney disease v5.8 OFD1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: Although renal cysts are present in around half of the cases reported in PMID:11179005 (and associated with Orofaciodigital syndrome I, MIM #311200), they are syndromic cases./

As reviewed by Nour Elkhateeb, female patient reported in PMID:10910455 had renal cysts are the only apparent manifestation.

Hence, this gene can be promoted from red to amber with the current evidence.; to: Comment on list classification: Although renal cysts are present in around half of the cases reported in PMID:11179005 (and associated with Orofaciodigital syndrome I, MIM #311200), they are syndromic.

As reviewed by Nour Elkhateeb, female patient reported in PMID:10910455 had renal cysts are the only apparent manifestation.

Hence, this gene can be promoted from red to amber with the current evidence.
Cystic kidney disease v5.8 OFD1 Achchuthan Shanmugasundram Classified gene: OFD1 as Amber List (moderate evidence)
Cystic kidney disease v5.8 OFD1 Achchuthan Shanmugasundram Added comment: Comment on list classification: Although renal cysts are present in around half of the cases reported in PMID:11179005 (and associated with Orofaciodigital syndrome I, MIM #311200), they are syndromic cases./

As reviewed by Nour Elkhateeb, female patient reported in PMID:10910455 had renal cysts are the only apparent manifestation.

Hence, this gene can be promoted from red to amber with the current evidence.
Cystic kidney disease v5.8 OFD1 Achchuthan Shanmugasundram Gene: ofd1 has been classified as Amber List (Moderate Evidence).
Primary ciliary disorders v1.42 WFDC2 Max Xiaohang Zhao gene: WFDC2 was added
gene: WFDC2 was added to Primary ciliary disorders. Sources: Literature
Mode of inheritance for gene: WFDC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WFDC2 were set to 38626355
Phenotypes for gene: WFDC2 were set to Nasal Polyposis; Bronchiectasis
Penetrance for gene: WFDC2 were set to unknown
Review for gene: WFDC2 was set to RED
gene: WFDC2 was marked as current diagnostic
Added comment: Sources: Literature
Cystic kidney disease v5.7 OFD1 Achchuthan Shanmugasundram Publications for gene: OFD1 were set to
Fetal anomalies v4.23 USP14 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There are four unrelated families snd functional evidence in support of the association of this gene to this panel. Hence, this gene can be promoted to green rating in the next GMS review.; to: Comment on list classification: There are four unrelated families and functional evidence in support of the association of this gene to this panel. Hence, this gene can be promoted to green rating in the next GMS review.
Fetal anomalies v4.23 USP14 Achchuthan Shanmugasundram Classified gene: USP14 as Amber List (moderate evidence)
Fetal anomalies v4.23 USP14 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are four unrelated families snd functional evidence in support of the association of this gene to this panel. Hence, this gene can be promoted to green rating in the next GMS review.
Fetal anomalies v4.23 USP14 Achchuthan Shanmugasundram Gene: usp14 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v4.22 USP14 Achchuthan Shanmugasundram Publications for gene: USP14 were set to 38469793
Fetal anomalies v4.21 USP14 Achchuthan Shanmugasundram Phenotypes for gene: USP14 were changed from Syndromic disease MONDO:0002254, USP14-related to syndromic disease, MONDO:0002254; distal arthrogryposis, MONDO:0019942
Fetal anomalies v4.20 USP14 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: USP14.
Fetal anomalies v4.20 USP14 Achchuthan Shanmugasundram reviewed gene: USP14: Rating: GREEN; Mode of pathogenicity: None; Publications: 35066879, 38469793; Phenotypes: syndromic disease, MONDO:0002254, distal arthrogryposis, MONDO:0019942; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v4.20 MDFIC Achchuthan Shanmugasundram Classified gene: MDFIC as Amber List (moderate evidence)
Fetal anomalies v4.20 MDFIC Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (six unrelated cases and functional evidence) for the promotion of this gene to green rating in the next GMS update.
Fetal anomalies v4.20 MDFIC Achchuthan Shanmugasundram Gene: mdfic has been classified as Amber List (Moderate Evidence).
Fetal anomalies v4.19 MDFIC Achchuthan Shanmugasundram Phenotypes for gene: MDFIC were changed from conducting lymphatic anomaly with lymphedema to Lymphatic malformation 12, OMIM:620014
Fetal anomalies v4.18 MDFIC Achchuthan Shanmugasundram Publications for gene: MDFIC were set to PMID: 35235341
Fetal anomalies v4.17 MDFIC Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: MDFIC.
Fetal anomalies v4.17 MDFIC Achchuthan Shanmugasundram reviewed gene: MDFIC: Rating: GREEN; Mode of pathogenicity: None; Publications: 35235341; Phenotypes: Lymphatic malformation 12, OMIM:620014; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v4.17 KCNK9 Achchuthan Shanmugasundram Tag Q2_24_NHS_review tag was added to gene: KCNK9.
Fetal anomalies v4.17 KCNT1 Achchuthan Shanmugasundram Classified gene: KCNT1 as Amber List (moderate evidence)
Fetal anomalies v4.17 KCNT1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Sarah Graham, PMID:36307859 reported a foetus with increased nuchal translucency and bilateral choroid plexus cysts. Hence, the rating can be updated from red to amber.
Fetal anomalies v4.17 KCNT1 Achchuthan Shanmugasundram Gene: kcnt1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v4.16 KCNT1 Achchuthan Shanmugasundram Mode of inheritance for gene: KCNT1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v4.15 KCNK9 Achchuthan Shanmugasundram Classified gene: KCNK9 as Amber List (moderate evidence)
Fetal anomalies v4.15 KCNK9 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are several unrelated cases reported with KCNK9 variants and Birk-Barel syndrome (MIM #612292). Clinical presentations include motor and speech delay, impaired intellectual development, early feeding difficulties, muscular hypotonia, behavioral abnormalities and dysmorphic features.

In addition, this gene has also been associated with phenotypes on the DD panel of Gene2Phenotype resource with 'limited' rating.

As reviewed by Sarah Graham, a foetus has also been reported with KCNK9 variant and with phenotypes consistent with this disorder.

Hence, this gene can be promoted to green rating in the next GMS update.
Fetal anomalies v4.15 KCNK9 Achchuthan Shanmugasundram Gene: kcnk9 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v4.14 KCNK9 Achchuthan Shanmugasundram Phenotypes for gene: KCNK9 were changed from to Birk-Barel syndrome, OMIM:612292
Fetal anomalies v4.13 KCNK9 Achchuthan Shanmugasundram Publications for gene: KCNK9 were set to PMID: 36307859
Fetal anomalies v4.12 KCNK9 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: KCNK9.
Fetal anomalies v4.12 KCNK9 Achchuthan Shanmugasundram reviewed gene: KCNK9: Rating: GREEN; Mode of pathogenicity: None; Publications: 36307859; Phenotypes: Birk-Barel syndrome, OMIM:612292; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Fetal anomalies v4.12 GNB2 Achchuthan Shanmugasundram Tag Q2_24_NHS_review tag was added to gene: GNB2.
Fetal anomalies v4.12 GNB2 Achchuthan Shanmugasundram Classified gene: GNB2 as Amber List (moderate evidence)
Fetal anomalies v4.12 GNB2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Sarah Graham, monoallelic GNB2 variants are associated with a neurodevelopmental disorder with features including dysmorphic facial features, cardiac and renal abnormalities.

This gene has been associated with phenotypes in OMIM (MIM #619503) and DD panel of Gene2Phenotype resource (with 'Definitive' rating, previously known as 'confirmed').

A foetus was also reported with phenotypes consistent with this gene.

Hence, this gene can be promoted to green rating in the next GMS update.
Fetal anomalies v4.12 GNB2 Achchuthan Shanmugasundram Gene: gnb2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v4.11 GNB2 Achchuthan Shanmugasundram Phenotypes for gene: GNB2 were changed from to Neurodevelopmental disorder with hypotonia and dysmorphic facies, OMIM:619503
Fetal anomalies v4.10 GNB2 Achchuthan Shanmugasundram Publications for gene: GNB2 were set to 36658419
Fetal anomalies v4.9 GNB2 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: GNB2.
Fetal anomalies v4.9 GNB2 Achchuthan Shanmugasundram reviewed gene: GNB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31698099, 34183358, 36658419; Phenotypes: Neurodevelopmental disorder with hypotonia and dysmorphic facies, OMIM:619503; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v4.9 CLCN5 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: AS reviewed by Sarah Graham, this gene has been rated red in this panel.; to: Comment on list classification: As reviewed by Sarah Graham, this gene has been rated red in this panel.
Fetal anomalies v4.9 CLCN5 Achchuthan Shanmugasundram Classified gene: CLCN5 as Red List (low evidence)
Fetal anomalies v4.9 CLCN5 Achchuthan Shanmugasundram Added comment: Comment on list classification: AS reviewed by Sarah Graham, this gene has been rated red in this panel.
Fetal anomalies v4.9 CLCN5 Achchuthan Shanmugasundram Gene: clcn5 has been classified as Red List (Low Evidence).
Fetal anomalies v4.8 CLCN5 Achchuthan Shanmugasundram Classified gene: CLCN5 as Red List (low evidence)
Fetal anomalies v4.8 CLCN5 Achchuthan Shanmugasundram Gene: clcn5 has been classified as Red List (Low Evidence).
Fetal anomalies v4.7 ARV1 Achchuthan Shanmugasundram Classified gene: ARV1 as Amber List (moderate evidence)
Fetal anomalies v4.7 ARV1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Sarah Graham, there are four cases from three different families (including two foetuses from a single family) reported with biallelic ARV1 variants and prenatal abnormalities. However, it should be noted that multiple major structural anomalies were not reported in these cases. Hence, this gene should be rated amber with the current evidence.
Fetal anomalies v4.7 ARV1 Achchuthan Shanmugasundram Gene: arv1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v4.6 ARV1 Achchuthan Shanmugasundram Phenotypes for gene: ARV1 were changed from to Developmental and epileptic encephalopathy 38, OMIM:617020
Fetal anomalies v4.5 ARV1 Achchuthan Shanmugasundram Publications for gene: ARV1 were set to PMID: 36307859; 34296759
Fetal anomalies v4.4 ARV1 Achchuthan Shanmugasundram reviewed gene: ARV1: Rating: AMBER; Mode of pathogenicity: None; Publications: 34296759, 36307859; Phenotypes: Developmental and epileptic encephalopathy 38, OMIM:617020; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cystic kidney disease v5.6 CLCN5 Sarah Leigh Tag Q2_24_promote_green tag was added to gene: CLCN5.
Tag Q2_24_NHS_review tag was added to gene: CLCN5.
Cystic kidney disease v5.6 CLCN5 Sarah Leigh Publications for gene: CLCN5 were set to 7922301; 37641036
Cystic kidney disease v5.5 CLCN5 Sarah Leigh reviewed gene: CLCN5: Rating: GREEN; Mode of pathogenicity: None; Publications: 8559248, 9259268, 9187673, 9602200, 14569459, 16041495, 16247550, 19673950; Phenotypes: ; Mode of inheritance: None
Fetal anomalies v4.4 CLCN5 Sarah Leigh Phenotypes for gene: CLCN5 were changed from to Dent disease 1, OMIM:300009; Hypophosphatemic rickets, OMIM:300554; Nephrolithiasis, type I, OMIM:310468; Proteinuria, low molecular weight, with hypercalciuric nephrocalcinosis, OMIM:308990
Cystic kidney disease v5.5 CLCN5 Sarah Leigh Phenotypes for gene: CLCN5 were changed from cystic kdiney disease; cortical cysts; medullary cysts; nephrocalcinosis; low molecular weight proteinuria; hypercalciuria to Dent disease 1, OMIM:300009; Hypophosphatemic rickets, OMIM:300554; Nephrolithiasis, type I, OMIM:310468; Proteinuria, low molecular weight, with hypercalciuric nephrocalcinosis, OMIM:308990
Cystic kidney disease v5.4 CLCN5 Sarah Leigh Classified gene: CLCN5 as Amber List (moderate evidence)
Cystic kidney disease v5.4 CLCN5 Sarah Leigh Gene: clcn5 has been classified as Amber List (Moderate Evidence).
Intellectual disability v6.40 SOX9 Sarah Leigh Tag Q2_24_demote_amber tag was added to gene: SOX9.
Tag Q2_24_NHS_review tag was added to gene: SOX9.
Intellectual disability v6.40 SOX9 Sarah Leigh reviewed gene: SOX9: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v6.40 SOX9 Sarah Leigh Phenotypes for gene: SOX9 were changed from Campomelic dysplasia with autosomal sex reversal, 114290; Acampomelic campomelic dysplasia, 114290; Campomelic dysplasia, 114290; intellectual disability to Campomelic dysplasia with autosomal sex reversal, OMIM:114290; Acampomelic campomelic dysplasia, OMIM:114290; Campomelic dysplasia, OMIM:114290; campomelic dysplasia, MONDO:0007251
DDG2P v4.6 AFF2 Sarah Leigh Publications for gene: AFF2 were set to 8334699; 8023854; 21739600; 9299237; 11171404; 11923441; 19136466; 2356291
Intellectual disability v6.39 AFF2 Sarah Leigh Publications for gene: AFF2 were set to 25529582; 24896178; 8334699; 8023854; 21739600; 9299237; 11171404; 11923441; 19136466; 2356291
DDG2P v4.5 AFF2 Sarah Leigh edited their review of gene: AFF2: Added comment: Intellectual developmental disorder, X-linked 109 (OMIM:3095480, is also associated with deletions of AFF2. Stettner et al. (PMID: 21739600) describe 2 brothers with OMIM:3095480, who have a 121 to 145-kb intragenic deletion within AFF2, while Sahoo et al (PMID: 22065534) report two unrelated males with OMIM:3095480; Patient 1 has a 240 kb intragenic deletion resulting the loss of exons 2-4 of AFF2 and Patient 2 has a 499 kb deletion that removes the exons 1-2.; Changed publications to: 21739600, 22065534
Intellectual disability v6.38 AFF2 Sarah Leigh edited their review of gene: AFF2: Added comment: Intellectual developmental disorder, X-linked 109 (OMIM:3095480, is also associated with deletions of AFF2. Stettner et al. (PMID: 21739600) describe 2 brothers with OMIM:3095480, who have a 121 to 145-kb intragenic deletion within AFF2, while Sahoo et al (PMID: 22065534) report two unrelated males with OMIM:3095480; Patient 1 has a 240 kb intragenic deletion resulting the loss of exons 2-4 of AFF2 and Patient 2 has a 499 kb deletion that removes the exons 1-2.; Changed publications to: 21739600, 22065534
Hereditary neuropathy v1.480 ATXN7_CAG Sarah Leigh Classified STR: ATXN7_CAG as Green List (high evidence)
Hereditary neuropathy v1.480 ATXN7_CAG Sarah Leigh Str: atxn7_cag has been classified as Green List (High Evidence).
Hereditary neuropathy v1.479 ATXN7_CAG Sarah Leigh Tag Q2_24_promote_green was removed from STR: ATXN7_CAG.
Tag Q2_24_expert_review was removed from STR: ATXN7_CAG.
Adult onset neurodegenerative disorder v5.7 ATXN7_CAG Sarah Leigh Phenotypes for STR: ATXN7_CAG were changed from Spinocerebellar ataxia 7, OMIM:164500 to Spinocerebellar ataxia 7, OMIM:164500; autosomal dominant cerebellar ataxia type II, MONDO:0016163
Hereditary neuropathy v1.479 ATXN7_CAG Sarah Leigh Phenotypes for STR: ATXN7_CAG were changed from Spinocerebellar ataxia 7, OMIM:164500 to Spinocerebellar ataxia 7, OMIM:164500; autosomal dominant cerebellar ataxia type II, MONDO:0016163
Adult onset neurodegenerative disorder v5.6 ATXN7_CAG Sarah Leigh Tag watchlist was removed from STR: ATXN7_CAG.
Tag Q2_24_promote_green tag was added to STR: ATXN7_CAG.
Tag Q2_24_expert_review tag was added to STR: ATXN7_CAG.
Hereditary neuropathy v1.478 ATXN7_CAG Sarah Leigh Tag Q2_24_promote_green tag was added to STR: ATXN7_CAG.
Tag Q2_24_expert_review tag was added to STR: ATXN7_CAG.
Retinal disorders v5.15 ATXN7_CAG Sarah Leigh Tag STR tag was added to STR: ATXN7_CAG.
Tag Q2_24_promote_green tag was added to STR: ATXN7_CAG.
Tag Q2_24_NHS_review tag was added to STR: ATXN7_CAG.
Adult onset neurodegenerative disorder v5.6 ATXN7_CAG Sarah Leigh reviewed STR: ATXN7_CAG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Hereditary neuropathy v1.478 ATXN7_CAG Sarah Leigh reviewed STR: ATXN7_CAG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Retinal disorders v5.15 ATXN7_CAG Sarah Leigh reviewed STR: ATXN7_CAG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Retinal disorders v5.15 ATXN7_CAG Sarah Leigh Publications for STR: ATXN7_CAG were set to 27632585
Retinal disorders v5.14 ATXN7_CAG Sarah Leigh Classified STR: ATXN7_CAG as Amber List (moderate evidence)
Retinal disorders v5.14 ATXN7_CAG Sarah Leigh Str: atxn7_cag has been classified as Amber List (Moderate Evidence).
Retinal disorders v5.13 ATXN7_CAG Sarah Leigh Phenotypes for STR: ATXN7_CAG were changed from Maculopaty; Cone-Rod Dystrophy to Spinocerebellar ataxia 7, OMIM:164500; autosomal dominant cerebellar ataxia type II, MONDO:0016163
Retinal disorders v5.12 ATXN7_CAG Sarah Leigh Publications for STR: ATXN7_CAG were set to PMID: 27632585,
Adult onset neurodegenerative disorder v5.6 ATXN2_CAG Sarah Leigh Tag watchlist was removed from STR: ATXN2_CAG.
Adult onset neurodegenerative disorder v5.6 ATXN2_CAG Sarah Leigh Tag Q2_24_promote_green tag was added to STR: ATXN2_CAG.
Tag Q2_24_NHS_review tag was added to STR: ATXN2_CAG.
Adult onset neurodegenerative disorder v5.6 ATXN2_CAG Sarah Leigh changed review comment from: Numerous instances of ATXN2_CAG repeat expansions have been reported in the literature associated with Amyotrophic lateral sclerosis, susceptibility to, 13 (OMIM:183090)(PMID: 20740007;21479228;21537950;21562247;21610160).; to: Numerous instances of ATXN2_CAG repeat expansions have been reported in the literature associated with Amyotrophic lateral sclerosis, susceptibility to, 13 (OMIM:183090), which is an adult onset neurodegenerative disorder (PMID: 20740007;21479228;21537950;21562247;21610160).
Adult onset neurodegenerative disorder v5.6 ATXN2_CAG Sarah Leigh edited their review of STR: ATXN2_CAG: Added comment: Numerous instances of ATXN2_CAG repeat expansions have been reported in the literature associated with Amyotrophic lateral sclerosis, susceptibility to, 13 (OMIM:183090)(PMID: 20740007;21479228;21537950;21562247;21610160).; Changed rating: GREEN
Adult onset neurodegenerative disorder v5.6 ATXN2_CAG Sarah Leigh Deleted their comment
Adult onset neurodegenerative disorder v5.6 ATXN2_CAG Sarah Leigh Publications for STR: ATXN2_CAG were set to 20740007; 21479228; 21537950; 21562247
Adult onset neurodegenerative disorder v5.5 ATXN2_CAG Sarah Leigh Added comment: Comment on phenotypes: Spinocerebellar ataxia 2, OMIM:183090;{Amyotrophic lateral sclerosis, susceptibility to, 13}, OMIM:183090;spinocerebellar ataxia type 2,
MONDO:0008458; {Parkinson disease, late-onset, susceptibility to}, OMIM:168600
Adult onset neurodegenerative disorder v5.5 ATXN2_CAG Sarah Leigh Phenotypes for STR: ATXN2_CAG were changed from Spinocerebellar ataxia 2, OMIM:183090; {Amyotrophic lateral sclerosis, susceptibility to, 13}, OMIM:183090; {Parkinson disease, late-onset, susceptibility to}, OMIM:168600 to Spinocerebellar ataxia 2, OMIM:183090; {Amyotrophic lateral sclerosis, susceptibility to, 13}, OMIM:183090; {Parkinson disease, late-onset, susceptibility to}, OMIM:168600
Adult onset neurodegenerative disorder v5.4 ATXN2_CAG Sarah Leigh Publications for STR: ATXN2_CAG were set to
Monogenic hearing loss v4.43 PLXNB2 Achchuthan Shanmugasundram Deleted their comment
Monogenic hearing loss v4.43 PLXNB2 Achchuthan Shanmugasundram Classified gene: PLXNB2 as Amber List (moderate evidence)
Monogenic hearing loss v4.43 PLXNB2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reported in PMID:38458752, there are seven patients from five different families (from a total of eight patients from six families) reported with sensorineural hearing loss. Hence, this gene can be promoted to green rating in the next GMS update.
Monogenic hearing loss v4.43 PLXNB2 Achchuthan Shanmugasundram Gene: plxnb2 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v4.43 PLXNB2 Achchuthan Shanmugasundram Classified gene: PLXNB2 as Amber List (moderate evidence)
Monogenic hearing loss v4.43 PLXNB2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reported in PMID:38458752, there are seven patients from five different families (from a total of eight patients from six families) reported with sensorineural hearing loss. Hence, this gene can be promoted to green rating in the next GMS update.
Monogenic hearing loss v4.43 PLXNB2 Achchuthan Shanmugasundram Gene: plxnb2 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v4.42 PLXNB2 Achchuthan Shanmugasundram reviewed gene: PLXNB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 38458752; Phenotypes: amelogenesis imperfecta, MONDO:0019507, sensorineural hearing loss disorder, MONDO:0020678, intellectual disability, MONDO:0001071; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v4.42 PLXNB2 Achchuthan Shanmugasundram Deleted their review
Monogenic hearing loss v4.42 PLXNB2 Achchuthan Shanmugasundram Entity copied from Intellectual disability v6.38
Monogenic hearing loss v4.42 PLXNB2 Achchuthan Shanmugasundram gene: PLXNB2 was added
gene: PLXNB2 was added to Monogenic hearing loss. Sources: Expert Review Amber,Literature
Q2_24_promote_green tags were added to gene: PLXNB2.
Mode of inheritance for gene: PLXNB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLXNB2 were set to 38458752
Phenotypes for gene: PLXNB2 were set to amelogenesis imperfecta, MONDO:0019507; sensorineural hearing loss disorder, MONDO:0020678; intellectual disability, MONDO:0001071
Intellectual disability v6.38 PLXNB2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v6.38 PLXNB2 Achchuthan Shanmugasundram Classified gene: PLXNB2 as Amber List (moderate evidence)
Intellectual disability v6.38 PLXNB2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reported in PMID:38458752 and reviewed by Claire Smith, there are six patients from four different families (from a total of eight patients from six families) reported with intellectual disability. Hence, this gene can be promoted to green rating in the next GMS update.
Intellectual disability v6.38 PLXNB2 Achchuthan Shanmugasundram Gene: plxnb2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v6.38 PLXNB2 Achchuthan Shanmugasundram Classified gene: PLXNB2 as Amber List (moderate evidence)
Intellectual disability v6.38 PLXNB2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reported in PMID:38458752 and reviewed by Claire Smith, there are six patients from four different families (from a total of eight patients from six families) reported with intellectual disability. Hence, this gene can be promoted to green rating in the next GMS update.
Intellectual disability v6.38 PLXNB2 Achchuthan Shanmugasundram Gene: plxnb2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v6.37 PLXNB2 Achchuthan Shanmugasundram Phenotypes for gene: PLXNB2 were changed from amelogenesis imperfecta, MONDO:0019507; sensorineural hearing loss disorder, MONDO:0020678; intellectual disability, MONDO:0001071 to amelogenesis imperfecta, MONDO:0019507; sensorineural hearing loss disorder, MONDO:0020678; intellectual disability, MONDO:0001071
Intellectual disability v6.37 PLXNB2 Achchuthan Shanmugasundram Phenotypes for gene: PLXNB2 were changed from amelogenesis imperfecta, MONDO:0019507; sensorineural hearing loss disorder, MONDO:0020678; intellectual disability, MONDO:0001071 to amelogenesis imperfecta, MONDO:0019507; sensorineural hearing loss disorder, MONDO:0020678; intellectual disability, MONDO:0001071
Intellectual disability v6.37 PLXNB2 Achchuthan Shanmugasundram Phenotypes for gene: PLXNB2 were changed from amelogenesis imperfecta, MONDO:0019507; sensorineural hearing loss disorder, MONDO:0020678; intellectual disability, MONDO:0001071 to amelogenesis imperfecta, MONDO:0019507; sensorineural hearing loss disorder, MONDO:0020678; intellectual disability, MONDO:0001071
Intellectual disability v6.37 PLXNB2 Achchuthan Shanmugasundram Phenotypes for gene: PLXNB2 were changed from amelogenesis imperfecta, MONDO:0019507; sensorineural hearing loss disorder, MONDO:0020678; intellectual disability, MONDO:0001071 to amelogenesis imperfecta, MONDO:0019507; sensorineural hearing loss disorder, MONDO:0020678; intellectual disability, MONDO:0001071
Intellectual disability v6.37 PLXNB2 Achchuthan Shanmugasundram Phenotypes for gene: PLXNB2 were changed from Syndromic disease MONDO:0002254, PLXNB2 -related to amelogenesis imperfecta, MONDO:0019507; sensorineural hearing loss disorder, MONDO:0020678; intellectual disability, MONDO:0001071
Intellectual disability v6.36 PLXNB2 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: PLXNB2.
Intellectual disability v6.36 PLXNB2 Achchuthan Shanmugasundram reviewed gene: PLXNB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 38458752; Phenotypes: amelogenesis imperfecta, MONDO:0019507, sensorineural hearing loss disorder, MONDO:0020678, intellectual disability, MONDO:0001071; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder v4.6 MT-TT Sarah Leigh Classified gene: MT-TT as No list
Childhood onset dystonia, chorea or related movement disorder v4.6 MT-TT Sarah Leigh Added comment: Comment on list classification: On 18 Aug 2020, the status of MT-TT on the Childhood onset dystonia, chorea or related movement disorder panel was changed from Red to Grey (curator removed), based on a request from NHS England that this Mitochondrial gene should be removed from the panel. Would it be relevant to promote MT-TT to Green, now that there is further evidence to support the association between MT-TT variants and human disease?
Childhood onset dystonia, chorea or related movement disorder v4.6 MT-TT Sarah Leigh Gene: mt-tt has been removed from the panel.
Childhood onset dystonia, chorea or related movement disorder v4.5 MT-TT Sarah Leigh reviewed gene: MT-TT: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Childhood onset dystonia, chorea or related movement disorder v4.5 MT-TT Sarah Leigh Tag Q2_24_promote_green tag was added to gene: MT-TT.
Tag Q2_24_expert_review tag was added to gene: MT-TT.
Amelogenesis imperfecta v3.6 PLXNB2 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reported in PMID:38458752 and reviewed by Claire Smith, there are seven patients from five different families (from a total of eight patients from six families) reported with amelogenesis imperfect. Hence, this gene can be promoted to green rating in the next GMS update.; to: Comment on list classification: As reported in PMID:38458752 and reviewed by Claire Smith, there are seven patients from five different families (from a total of eight patients from six families) reported with amelogenesis imperfecta. Hence, this gene can be promoted to green rating in the next GMS update.
Amelogenesis imperfecta v3.6 PLXNB2 Achchuthan Shanmugasundram Classified gene: PLXNB2 as Amber List (moderate evidence)
Amelogenesis imperfecta v3.6 PLXNB2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reported in PMID:38458752 and reviewed by Claire Smith, there are seven patients from five different families (from a total of eight patients from six families) reported with amelogenesis imperfect. Hence, this gene can be promoted to green rating in the next GMS update.
Amelogenesis imperfecta v3.6 PLXNB2 Achchuthan Shanmugasundram Gene: plxnb2 has been classified as Amber List (Moderate Evidence).
Amelogenesis imperfecta v3.5 PLXNB2 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: PLXNB2.
Amelogenesis imperfecta v3.5 PLXNB2 Achchuthan Shanmugasundram Phenotypes for gene: PLXNB2 were changed from Amelogenesis imperfecta; sensorineural hearing loss to amelogenesis imperfecta, MONDO:0019507; sensorineural hearing loss disorder, MONDO:0020678; intellectual disability, MONDO:0001071
Amelogenesis imperfecta v3.4 PLXNB2 Achchuthan Shanmugasundram Publications for gene: PLXNB2 were set to PMID: 38458752
Amelogenesis imperfecta v3.3 PLXNB2 Achchuthan Shanmugasundram reviewed gene: PLXNB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 38458752; Phenotypes: amelogenesis imperfecta, MONDO:0019507, sensorineural hearing loss disorder, MONDO:0020678, intellectual disability, MONDO:0001071; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder v4.5 MT-TT Sarah Leigh Publications for gene: MT-TT were set to
Paediatric or syndromic cardiomyopathy v4.10 CAMK2D Achchuthan Shanmugasundram Deleted their comment
Paediatric or syndromic cardiomyopathy v4.10 CAMK2D Achchuthan Shanmugasundram Deleted their comment
Paediatric or syndromic cardiomyopathy v4.10 CAMK2D Achchuthan Shanmugasundram Classified gene: CAMK2D as Amber List (moderate evidence)
Paediatric or syndromic cardiomyopathy v4.10 CAMK2D Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (six with DCM, four of six with age below 12 years, and functional evidence) for the promotion of this gene to green rating in the next GMS update.
Paediatric or syndromic cardiomyopathy v4.10 CAMK2D Achchuthan Shanmugasundram Gene: camk2d has been classified as Amber List (Moderate Evidence).
Paediatric or syndromic cardiomyopathy v4.9 CAMK2D Achchuthan Shanmugasundram Classified gene: CAMK2D as Amber List (moderate evidence)
Paediatric or syndromic cardiomyopathy v4.9 CAMK2D Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (six with DCM, four of six with age below 12 years, and functional evidence) for the promotion of this gene to green rating in the next GMS update.
Paediatric or syndromic cardiomyopathy v4.9 CAMK2D Achchuthan Shanmugasundram Gene: camk2d has been classified as Amber List (Moderate Evidence).
Paediatric or syndromic cardiomyopathy v4.9 CAMK2D Achchuthan Shanmugasundram Classified gene: CAMK2D as Amber List (moderate evidence)
Paediatric or syndromic cardiomyopathy v4.9 CAMK2D Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (six with DCM, four of six with age below 12 years, and functional evidence) for the promotion of this gene to green rating in the next GMS update.
Paediatric or syndromic cardiomyopathy v4.9 CAMK2D Achchuthan Shanmugasundram Gene: camk2d has been classified as Amber List (Moderate Evidence).
Paediatric or syndromic cardiomyopathy v4.8 CAMK2D Achchuthan Shanmugasundram changed review comment from: PMID:38272033 reported eight unrelated individuals with monoallelic CAMK2D variants and presenting with a neurodevelopmental disorder. Clinical phenotypes include intellectual disability (ID), delayed speech, behavioral problems and dilated cardiomyopathy.

The majority of the variants tested lead to a gain of function (GoF), which appears to cause both neurological problems and dilated cardiomyopathy. In contrast, loss-of-function (LoF) variants appear to induce only neurological symptoms.

Dilated cardiomyopathy was reported in six of eight reported cases and their age ranged from five weeks to 20 years (with four of six DCM patients with age below 12 years).

This gene has been associated with relevant phenotype in Gene2Phenotype ('moderate' rating on the DD panel), but not yet in OMIM.
Sources: Literature; to: PMID:38272033 reported eight unrelated individuals with monoallelic CAMK2D variants and presenting with a neurodevelopmental disorder. Clinical phenotypes include intellectual disability (ID), delayed speech, behavioral problems and dilated cardiomyopathy.

The majority of the variants tested lead to a gain of function (GoF), which appears to cause both neurological problems and dilated cardiomyopathy. In contrast, loss-of-function (LoF) variants appear to induce only neurological symptoms.

Dilated cardiomyopathy was reported in six of eight reported cases and their age ranged from five weeks to 20 years (four of six DCM patients with age below 12 years).

This gene has been associated with relevant phenotype in Gene2Phenotype ('moderate' rating on the DD panel), but not yet in OMIM.
Sources: Literature
Paediatric or syndromic cardiomyopathy v4.8 CAMK2D Achchuthan Shanmugasundram gene: CAMK2D was added
gene: CAMK2D was added to Paediatric or syndromic cardiomyopathy. Sources: Literature
Q2_24_promote_green tags were added to gene: CAMK2D.
Mode of inheritance for gene: CAMK2D was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CAMK2D were set to 38272033
Phenotypes for gene: CAMK2D were set to neurodevelopmental disorder, MONDO:0700092; dilated cardiomyopathy, MONDO:0005021
Mode of pathogenicity for gene: CAMK2D 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: CAMK2D was set to GREEN
Added comment: PMID:38272033 reported eight unrelated individuals with monoallelic CAMK2D variants and presenting with a neurodevelopmental disorder. Clinical phenotypes include intellectual disability (ID), delayed speech, behavioral problems and dilated cardiomyopathy.

The majority of the variants tested lead to a gain of function (GoF), which appears to cause both neurological problems and dilated cardiomyopathy. In contrast, loss-of-function (LoF) variants appear to induce only neurological symptoms.

Dilated cardiomyopathy was reported in six of eight reported cases and their age ranged from five weeks to 20 years (with four of six DCM patients with age below 12 years).

This gene has been associated with relevant phenotype in Gene2Phenotype ('moderate' rating on the DD panel), but not yet in OMIM.
Sources: Literature
Early onset or syndromic epilepsy v5.16 CAMK2D Achchuthan Shanmugasundram Classified gene: CAMK2D as Amber List (moderate evidence)
Early onset or syndromic epilepsy v5.16 CAMK2D Achchuthan Shanmugasundram Gene: camk2d has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v5.16 CAMK2D Achchuthan Shanmugasundram Classified gene: CAMK2D as Amber List (moderate evidence)
Early onset or syndromic epilepsy v5.16 CAMK2D Achchuthan Shanmugasundram Gene: camk2d has been classified as Amber List (Moderate Evidence).
Intellectual disability v6.36 CAMK2D Achchuthan Shanmugasundram Deleted their comment
Early onset or syndromic epilepsy v5.16 CAMK2D Achchuthan Shanmugasundram Classified gene: CAMK2D as Amber List (moderate evidence)
Early onset or syndromic epilepsy v5.16 CAMK2D Achchuthan Shanmugasundram Gene: camk2d has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v5.15 CAMK2D Achchuthan Shanmugasundram gene: CAMK2D was added
gene: CAMK2D was added to Early onset or syndromic epilepsy. Sources: Literature
Mode of inheritance for gene: CAMK2D was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CAMK2D were set to 38272033
Phenotypes for gene: CAMK2D were set to neurodevelopmental disorder, MONDO:0700092; epilepsy, MONDO:0005027
Review for gene: CAMK2D was set to AMBER
Added comment: PMID:38272033 reported eight unrelated individuals with monoallelic CAMK2D variants and presenting with a neurodevelopmental disorder. Clinical phenotypes include intellectual disability (ID), delayed speech, behavioral problems and dilated cardiomyopathy.

The majority of the variants tested lead to a gain of function (GoF), which appears to cause both neurological problems and dilated cardiomyopathy. In contrast, loss-of-function (LoF) variants appear to induce only neurological symptoms.

Epilepsy was reported as one of the clinical manifestations in 3 out of eight reported cases.

This gene has been associated with relevant phenotype in Gene2Phenotype ('moderate' rating on the DD panel), but not yet in OMIM.
Sources: Literature
Intellectual disability v6.36 CAMK2D Achchuthan Shanmugasundram Classified gene: CAMK2D as Amber List (moderate evidence)
Intellectual disability v6.36 CAMK2D Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (seven unrelated cases) for the promotion of this gene to green rating in the next GMS update.
Intellectual disability v6.36 CAMK2D Achchuthan Shanmugasundram Gene: camk2d has been classified as Amber List (Moderate Evidence).
Intellectual disability v6.36 CAMK2D Achchuthan Shanmugasundram Classified gene: CAMK2D as Amber List (moderate evidence)
Intellectual disability v6.36 CAMK2D Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (seven unrelated cases) for the promotion of this gene to green rating in the next GMS update.
Intellectual disability v6.36 CAMK2D Achchuthan Shanmugasundram Gene: camk2d has been classified as Amber List (Moderate Evidence).
Intellectual disability v6.35 CAMK2D Achchuthan Shanmugasundram edited their review of gene: CAMK2D: Changed rating: GREEN
Intellectual disability v6.35 CAMK2D Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: CAMK2D.
Intellectual disability v6.35 CAMK2D Achchuthan Shanmugasundram gene: CAMK2D was added
gene: CAMK2D was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: CAMK2D was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CAMK2D were set to 38272033
Phenotypes for gene: CAMK2D were set to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Added comment: PMID:38272033 reported eight unrelated individuals with monoallelic CAMK2D variants and presenting with a neurodevelopmental disorder. Clinical phenotypes include intellectual disability (ID), delayed speech, behavioral problems and dilated cardiomyopathy.

The majority of the variants tested lead to a gain of function (GoF), which appears to cause both neurological problems and dilated cardiomyopathy. In contrast, loss-of-function (LoF) variants appear to induce only neurological symptoms.

ID was reported in all seven individuals tested for ID, where ID was mild in 2, moderate to severe in 1, severe in 3 and profound in 1 patient.

This gene has been associated with relevant phenotype in Gene2Phenotype ('moderate' rating on the DD panel), but not yet in OMIM.
Sources: Literature
Intellectual disability v6.34 EZH1 Achchuthan Shanmugasundram Classified gene: EZH1 as Amber List (moderate evidence)
Intellectual disability v6.34 EZH1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the association of both monoallelic and biallelic EZH1 variants to intellectual disability with green rating. Hence, this gene should be promoted to green in the next GMS update.
Intellectual disability v6.34 EZH1 Achchuthan Shanmugasundram Gene: ezh1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v6.33 EZH1 Achchuthan Shanmugasundram changed review comment from: PMID:37433783 reported 19 individuals from 14 unrelated families with a neurodevelopmental disorder manifested early in life as global motor, speech and cognitive delay leading to intellectual disability, usually non-progressive and co-occurring with dysmorphic facial features. Nine individuals from seven families were identified with monoallelic variants and ten individuals from seven families were identified with biallelic variants.

This gene has been associated with relevant phenotypes in Gene2Phenotype (both monoallelic and biallelic disorders rated 'moderate' on the DD panel), but not yet in OMIM.
Sources: Literature; to: PMID:37433783 reported 19 individuals from 14 unrelated families with a neurodevelopmental disorder manifested early in life as global motor, speech and cognitive delay leading to intellectual disability, usually non-progressive and co-occurring with dysmorphic facial features. Nine individuals from seven families were identified with monoallelic variants and ten individuals from seven families were identified with biallelic variants.

Functional studies have shown that some missense EZH1 variants lead to gain of function with increased methyltransferase activity and biallelic variants impair EZH1 expression leading to loss of function effects.

This gene has been associated with relevant phenotypes in Gene2Phenotype (both monoallelic and biallelic disorders rated 'moderate' on the DD panel), but not yet in OMIM.
Sources: Literature
Intellectual disability v6.33 EZH1 Achchuthan Shanmugasundram gene: EZH1 was added
gene: EZH1 was added to Intellectual disability. Sources: Literature
Q2_24_promote_green tags were added to gene: EZH1.
Mode of inheritance for gene: EZH1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: EZH1 were set to 37433783
Phenotypes for gene: EZH1 were set to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Mode of pathogenicity for gene: EZH1 was set to Other
Review for gene: EZH1 was set to GREEN
Added comment: PMID:37433783 reported 19 individuals from 14 unrelated families with a neurodevelopmental disorder manifested early in life as global motor, speech and cognitive delay leading to intellectual disability, usually non-progressive and co-occurring with dysmorphic facial features. Nine individuals from seven families were identified with monoallelic variants and ten individuals from seven families were identified with biallelic variants.

This gene has been associated with relevant phenotypes in Gene2Phenotype (both monoallelic and biallelic disorders rated 'moderate' on the DD panel), but not yet in OMIM.
Sources: Literature
Intellectual disability v6.32 YWHAE Achchuthan Shanmugasundram changed review comment from: PMID:36999555 reported three individuals with sequence variants in YWHAE gene and six individuals with deletion variants (1 intragenic deletion and 5 large deletions encompassing YWHEA but not PAFAH1B1). In addition, five patients were previously reported with deletion variants. Only one of the three individuals with sequence variants had mild intellectual disability, while five of 12 patients with deletion variants had mild to severe intellectual disability.
Sources: Literature; to: PMID:36999555 reported three individuals with sequence variants in YWHAE gene and six individuals with deletion variants (1 intragenic deletion and 5 large deletions encompassing YWHEA but not PAFAH1B1). In addition, five patients were previously reported with deletion variants. Only one of three individuals with sequence variants had mild intellectual disability, while five of 12 patients with deletion variants had mild to severe intellectual disability.
Sources: Literature
Intellectual disability v6.32 YWHAE Achchuthan Shanmugasundram gene: YWHAE was added
gene: YWHAE was added to Intellectual disability. Sources: Literature
cnv tags were added to gene: YWHAE.
Mode of inheritance for gene: YWHAE was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: YWHAE were set to 36999555
Phenotypes for gene: YWHAE were set to neurodevelopmental disorder, MONDO:0700092
Review for gene: YWHAE was set to RED
Added comment: PMID:36999555 reported three individuals with sequence variants in YWHAE gene and six individuals with deletion variants (1 intragenic deletion and 5 large deletions encompassing YWHEA but not PAFAH1B1). In addition, five patients were previously reported with deletion variants. Only one of the three individuals with sequence variants had mild intellectual disability, while five of 12 patients with deletion variants had mild to severe intellectual disability.
Sources: Literature
Intellectual disability v6.31 STX1A Achchuthan Shanmugasundram Classified gene: STX1A as Amber List (moderate evidence)
Intellectual disability v6.31 STX1A Achchuthan Shanmugasundram Added comment: Comment on list classification: There are six unrelated cases reported with monoallelic variants and two siblings reported with biallelic variants. Hence, the MOI was set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'. The rating should be updated to green in the next GMS update.
Intellectual disability v6.31 STX1A Achchuthan Shanmugasundram Gene: stx1a has been classified as Amber List (Moderate Evidence).
Intellectual disability v6.31 STX1A Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v6.31 STX1A Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v6.31 STX1A Achchuthan Shanmugasundram Classified gene: STX1A as Amber List (moderate evidence)
Intellectual disability v6.31 STX1A Achchuthan Shanmugasundram Added comment: Comment on list classification: There are six unrelated cases reported with monoallelic variants and two siblings reported with biallelic variants. Hence, the MOI was set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'. The rating should be updated to green in the next GMS update.
Intellectual disability v6.31 STX1A Achchuthan Shanmugasundram Gene: stx1a has been classified as Amber List (Moderate Evidence).
Intellectual disability v6.31 STX1A Achchuthan Shanmugasundram Classified gene: STX1A as Amber List (moderate evidence)
Intellectual disability v6.31 STX1A Achchuthan Shanmugasundram Added comment: Comment on list classification: There are six unrelated cases reported with monoallelic variants and two siblings reported with biallelic variants. Hence, the MOI was set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'. The rating should be updated to green in the next GMS update.
Intellectual disability v6.31 STX1A Achchuthan Shanmugasundram Gene: stx1a has been classified as Amber List (Moderate Evidence).
Intellectual disability v6.30 STX1A Achchuthan Shanmugasundram Classified gene: STX1A as Amber List (moderate evidence)
Intellectual disability v6.30 STX1A Achchuthan Shanmugasundram Added comment: Comment on list classification: There are six unrelated cases reported with monoallelic variants and two siblings reported with biallelic variants. Hence, the MOI was set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'. The rating should be updated to green in the next GMS update.
Intellectual disability v6.30 STX1A Achchuthan Shanmugasundram Gene: stx1a has been classified as Amber List (Moderate Evidence).
Intellectual disability v6.29 STX1A Achchuthan Shanmugasundram gene: STX1A was added
gene: STX1A was added to Intellectual disability. Sources: Literature
Q2_24_promote_green tags were added to gene: STX1A.
Mode of inheritance for gene: STX1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: STX1A were set to 36564538
Phenotypes for gene: STX1A were set to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Review for gene: STX1A was set to GREEN
Added comment: PMID:36564538 reported the identification of monoallelic STX1A variants in six unrelated individuals (five of them de novo and one unknown) and biallelic variants in two related individuals. All of them presented with a neurodevelopmental disorder and had intellectual disability (Both homozygous individuals had moderate ID, three heterozygous individuals had severe ID. one had profound ID and two had moderate ID).

This gene has been associated with relevant phenotype in Gene2Phenotype (with 'moderate' rating on the DD panel), but has not yet been associated with phenotypes in OMIM.
Sources: Literature
Monogenic short stature v0.180 SLF2 Achchuthan Shanmugasundram Classified gene: SLF2 as Amber List (moderate evidence)
Monogenic short stature v0.180 SLF2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (six unrelated cases) for the association of this gene with green rating in the next GMS update.
Monogenic short stature v0.180 SLF2 Achchuthan Shanmugasundram Gene: slf2 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v5.12 SLF2 Achchuthan Shanmugasundram Classified gene: SLF2 as Amber List (moderate evidence)
Severe microcephaly v5.12 SLF2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (six unrelated cases) for the association of this gene with green rating in the next GMS update.
Severe microcephaly v5.12 SLF2 Achchuthan Shanmugasundram Gene: slf2 has been classified as Amber List (Moderate Evidence).
Monogenic short stature v0.179 SLF2 Achchuthan Shanmugasundram gene: SLF2 was added
gene: SLF2 was added to Monogenic short stature. Sources: Literature
Q2_24_promote_green tags were added to gene: SLF2.
Mode of inheritance for gene: SLF2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLF2 were set to 36333305
Phenotypes for gene: SLF2 were set to Atelis syndrome 1, OMIM:620184
Review for gene: SLF2 was set to GREEN
Added comment: PMID:36333305 reported the identification of biallelic loss-of-function SLF2 variants in seven individuals from six different families with a chromosome breakage disorder. All these individuals had developmental delay, markedly Severe microcephaly and reduction in height. Functional data including zebrafish model is also available to support disease association.

This gene has been associated with relevant phenotype in both OMIM (MIM #620184) and Gene2Phenotype (with 'moderate' rating on the DD panel).
Sources: Literature
Severe microcephaly v5.11 SLF2 Achchuthan Shanmugasundram gene: SLF2 was added
gene: SLF2 was added to Severe microcephaly. Sources: Literature
Q2_24_promote_green tags were added to gene: SLF2.
Mode of inheritance for gene: SLF2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLF2 were set to 36333305
Phenotypes for gene: SLF2 were set to Atelis syndrome 1, OMIM:620184
Review for gene: SLF2 was set to GREEN
Added comment: PMID:36333305 reported the identification of biallelic loss-of-function SLF2 variants in seven individuals from six different families with a chromosome breakage disorder. All these individuals had developmental delay, markedly Severe microcephaly and reduction in height. Functional data including zebrafish model is also available to support disease association.

This gene has been associated with relevant phenotype in both OMIM (MIM #620184) and Gene2Phenotype (with 'moderate' rating on the DD panel).
Sources: Literature
Monogenic short stature v0.178 SMC5 Achchuthan Shanmugasundram Classified gene: SMC5 as Amber List (moderate evidence)
Monogenic short stature v0.178 SMC5 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (three unrelated cases) for the association of this gene with green rating in the next GMS update.
Monogenic short stature v0.178 SMC5 Achchuthan Shanmugasundram Gene: smc5 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v5.10 SMC5 Achchuthan Shanmugasundram Classified gene: SMC5 as Amber List (moderate evidence)
Severe microcephaly v5.10 SMC5 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (three unrelated cases) for the association of this gene with green rating in the next GMS update.
Severe microcephaly v5.10 SMC5 Achchuthan Shanmugasundram Gene: smc5 has been classified as Amber List (Moderate Evidence).
Monogenic short stature v0.177 SMC5 Achchuthan Shanmugasundram gene: SMC5 was added
gene: SMC5 was added to Monogenic short stature. Sources: Literature
Q2_24_promote_green tags were added to gene: SMC5.
Mode of inheritance for gene: SMC5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SMC5 were set to 36333305
Phenotypes for gene: SMC5 were set to Atelis syndrome 2, OMIM:620185
Review for gene: SMC5 was set to GREEN
Added comment: PMID:36333305 reported four individuals from three families with a chromosome breakage disorder and biallelic SMC5 variants. Three individuals from two families were identified with the same homozygous missense variant (p.His990Asp), while the other individual had compound heterozygous variants (p.Arg372del & p.Arg425Ter). All four patients presented with markedly severe microcephaly and reduction in height.

Evidence for functional impact of the variant was limited. However, zebrafish model recapitulated the phenotype and was not rescued by the introduction of this variant, arguing for functional effect.

This gene has been associated with relevant phenotype in both OMIM (MIM #620185) and Gene2Phenotype (with 'moderate' rating on the DD panel).
Sources: Literature
Severe microcephaly v5.9 SMC5 Achchuthan Shanmugasundram gene: SMC5 was added
gene: SMC5 was added to Severe microcephaly. Sources: Literature
Q2_24_promote_green tags were added to gene: SMC5.
Mode of inheritance for gene: SMC5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SMC5 were set to 36333305
Phenotypes for gene: SMC5 were set to Atelis syndrome 2, OMIM:620185
Review for gene: SMC5 was set to GREEN
Added comment: PMID:36333305 reported four individuals from three families with a chromosome breakage disorder and biallelic SMC5 variants. Three individuals from two families were identified with the same homozygous missense variant (p.His990Asp), while the other individual had compound heterozygous variants (p.Arg372del & p.Arg425Ter). All four patients presented with markedly severe microcephaly and reduction in height.

Evidence for functional impact of the variant was limited. However, zebrafish model recapitulated the phenotype and was not rescued by the introduction of this variant, arguing for functional effect.

This gene has been associated with relevant phenotype in both OMIM (MIM #620185) and Gene2Phenotype (with 'moderate' rating on the DD panel).
Sources: Literature
Intellectual disability v6.28 WDR5 Achchuthan Shanmugasundram Classified gene: WDR5 as Amber List (moderate evidence)
Intellectual disability v6.28 WDR5 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the association of this gene with green rating in the next GMS update.
Intellectual disability v6.28 WDR5 Achchuthan Shanmugasundram Gene: wdr5 has been classified as Amber List (Moderate Evidence).
Intellectual disability v6.28 WDR5 Achchuthan Shanmugasundram Classified gene: WDR5 as Amber List (moderate evidence)
Intellectual disability v6.28 WDR5 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the association of this gene with green rating in the next GMS update.
Intellectual disability v6.28 WDR5 Achchuthan Shanmugasundram Gene: wdr5 has been classified as Amber List (Moderate Evidence).
Intellectual disability v6.27 WDR5 Achchuthan Shanmugasundram gene: WDR5 was added
gene: WDR5 was added to Intellectual disability. Sources: Literature
Q2_24_promote_green tags were added to gene: WDR5.
Mode of inheritance for gene: WDR5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: WDR5 were set to 36408368
Phenotypes for gene: WDR5 were set to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Mode of pathogenicity for gene: WDR5 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: WDR5 was set to GREEN
Added comment: PMID:36408368 reported the identification of six different de novo missense variants in 11 affected individuals with a neurodevelopmental disorder with a broad spectrum of additional features, including epilepsy, aberrant growth parameters, skeletal and cardiac abnormalities. 9 of 11 probands have intellectual disability (five with moderate ID, three with mild ID and one with borderline ID).

In vivo and in vitro functional studies suggested that loss-of-function is not the mechanism of disease. However, the mechanism of disease is yet to be established.

This gene has been associated with relevant phenotype in Gene2Phenotype (with 'moderate' rating on the DD panel), but not associated with phenotypes in OMIM.
Sources: Literature
Likely inborn error of metabolism v5.22 CREB3L3 Achchuthan Shanmugasundram Deleted their comment
Likely inborn error of metabolism v5.17 ARSG Achchuthan Shanmugasundram Classified gene: ARSG as Amber List (moderate evidence)
Likely inborn error of metabolism v5.17 ARSG Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated green as it is green on 'Lysosomal storage disorder' panel (https://panelapp.genomicsengland.co.uk/panels/529/gene/ARSG/).
Likely inborn error of metabolism v5.15 ARSG Achchuthan Shanmugasundram Phenotypes for gene: ARSG were changed from Usher syndrome, type IV OMIM:618144; usher syndrome, type 4 MONDO:0029141 to Usher syndrome, type IV, OMIM:618144; usher syndrome, type 4, MONDO:0029141
Likely inborn error of metabolism v5.14 ARSG Achchuthan Shanmugasundram Publications for gene: ARSG were set to 26975023; 20679209; 25452429; 33300174
Likely inborn error of metabolism v5.13 ARSG Achchuthan Shanmugasundram Mode of inheritance for gene: ARSG was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v5.12 ARSG Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: ARSG.
Likely inborn error of metabolism v5.12 ARSG Achchuthan Shanmugasundram reviewed gene: ARSG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Usher syndrome, type IV, OMIM:618144; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v5.12 CREB3L3 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: CREB3L3.
Likely inborn error of metabolism v5.12 CREB3L3 Achchuthan Shanmugasundram Classified gene: CREB3L3 as Amber List (moderate evidence)
Likely inborn error of metabolism v5.12 CREB3L3 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be added with green rating on this panel as this gene has been rated green on 'Familial chylomicronaemia syndrome (FCS)' panel (https://panelapp.genomicsengland.co.uk/panels/527/gene/CREB3L3/).
Likely inborn error of metabolism v5.12 CREB3L3 Achchuthan Shanmugasundram Gene: creb3l3 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v5.11 CREB3L3 Achchuthan Shanmugasundram Classified gene: CREB3L3 as Amber List (moderate evidence)
Likely inborn error of metabolism v5.11 CREB3L3 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be added with green rating on this panel as this gene has been rated green on 'Familial chylomicronaemia syndrome (FCS)' panel (https://panelapp.genomicsengland.co.uk/panels/527/gene/CREB3L3/).
Likely inborn error of metabolism v5.11 CREB3L3 Achchuthan Shanmugasundram Gene: creb3l3 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v5.10 CREB3L3 Achchuthan Shanmugasundram Entity copied from Familial chylomicronaemia syndrome (FCS) v3.3
Likely inborn error of metabolism v5.10 CREB3L3 Achchuthan Shanmugasundram gene: CREB3L3 was added
gene: CREB3L3 was added to Likely inborn error of metabolism - targeted testing not possible. Sources: Expert Review Green,South West GLH,NHS GMS
Mode of inheritance for gene: CREB3L3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CREB3L3 were set to 29954705; 21666694; 26427795; 22135386
Phenotypes for gene: CREB3L3 were set to Hypertriglyceridemia 2, OMIM:619324; Hypertriglyceridemia (disease) MONDO:0005347
Likely inborn error of metabolism v5.9 PIGW Achchuthan Shanmugasundram Classified gene: PIGW as Amber List (moderate evidence)
Likely inborn error of metabolism v5.9 PIGW Achchuthan Shanmugasundram Gene: pigw has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v5.9 PIGW Achchuthan Shanmugasundram Classified gene: PIGW as Amber List (moderate evidence)
Likely inborn error of metabolism v5.9 PIGW Achchuthan Shanmugasundram Gene: pigw has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v5.9 PIGW Achchuthan Shanmugasundram Classified gene: PIGW as Amber List (moderate evidence)
Likely inborn error of metabolism v5.9 PIGW Achchuthan Shanmugasundram Gene: pigw has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v5.8 PIGW Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: PIGW.
Likely inborn error of metabolism v5.8 PIGW Achchuthan Shanmugasundram reviewed gene: PIGW: Rating: GREEN; Mode of pathogenicity: None; Publications: 24367057, 27626616, 30813920, 32198969; Phenotypes: Glycosylphosphatidylinositol biosynthesis defect 11 OMIM:616025, hyperphosphatasia with intellectual disability syndrome 5 MONDO:0014457; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.6 AQP2 Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: AQP2.
Unexplained young onset end-stage renal disease v4.6 AQP2 Achchuthan Shanmugasundram changed review comment from: This gene has been added with green rating to R257 Unexplained young onset end-stage renal disease panel as it has already been rated green in R198 Renal tubulopathies panel (https://panelapp.genomicsengland.co.uk/panels/292/).; to: This gene should be added with green rating to R257 Unexplained young onset end-stage renal disease panel as it has already been rated green in R198 Renal tubulopathies panel (https://panelapp.genomicsengland.co.uk/panels/292/).
Unexplained young onset end-stage renal disease v4.6 RCAN1 Achchuthan Shanmugasundram Entity copied from Proteinuric renal disease v4.12
Unexplained young onset end-stage renal disease v4.6 RCAN1 Achchuthan Shanmugasundram gene: RCAN1 was added
gene: RCAN1 was added to Unexplained young onset end-stage renal disease. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: RCAN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RCAN1 were set to 33863784
Phenotypes for gene: RCAN1 were set to focal segmental glomerulosclerosis, MONDO:0100313; nephrotic syndrome, MONDO:0005377
Unexplained young onset end-stage renal disease v4.5 PRDM15 Achchuthan Shanmugasundram Entity copied from Proteinuric renal disease v4.12
Unexplained young onset end-stage renal disease v4.5 PRDM15 Achchuthan Shanmugasundram gene: PRDM15 was added
gene: PRDM15 was added to Unexplained young onset end-stage renal disease. Sources: Expert Review Amber,Literature
Q2_24_promote_green tags were added to gene: PRDM15.
Mode of inheritance for gene: PRDM15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRDM15 were set to 31950080; 33593823
Phenotypes for gene: PRDM15 were set to steroid-resistant nephrotic syndrome, MONDO:0044765
Unexplained young onset end-stage renal disease v4.4 NOS1AP Achchuthan Shanmugasundram Entity copied from Proteinuric renal disease v4.12
Unexplained young onset end-stage renal disease v4.4 NOS1AP Achchuthan Shanmugasundram gene: NOS1AP was added
gene: NOS1AP was added to Unexplained young onset end-stage renal disease. Sources: Expert Review Amber,Literature
Q1_24_promote_green tags were added to gene: NOS1AP.
Mode of inheritance for gene: NOS1AP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NOS1AP were set to 33523862
Phenotypes for gene: NOS1AP were set to Nephrotic syndrome, type 22, OMIM:619155
Mitochondrial disorders v6.9 MT-TT Sarah Leigh Tag Q2_24_promote_green tag was added to gene: MT-TT.
Likely inborn error of metabolism v5.8 MT-TT Sarah Leigh Tag Q2_24_promote_green tag was added to gene: MT-TT.
Likely inborn error of metabolism v5.8 MT-TT Sarah Leigh Phenotypes for gene: MT-TT were changed from mitochondrial disease, MONDO:0044970; Leber optic atrophy, OMIM:535000; myoclonic epilepsy associated with ragged-red fibers, OMIM:545000; fatal infantile respiratory enzyme deficiency; Inherited Diabetes Mellitus; adult onset mild mypathy to mitochondrial disease, MONDO:0044970; Leber optic atrophy, OMIM:535000; myoclonic epilepsy associated with ragged-red fibers, OMIM:545000; fatal infantile respiratory enzyme deficiency; Inherited Diabetes Mellitus; adult onset mild myopathy
Mitochondrial disorders v6.9 MT-TT Sarah Leigh Phenotypes for gene: MT-TT were changed from mitochondrial disease, MONDO:0044970; Leber optic atrophy, OMIM:535000; myoclonic epilepsy associated with ragged-red fibers, OMIM:545000; fatal infantile respiratory enzyme deficiency; Inherited Diabetes Mellitus; adult onset mild mypathy to mitochondrial disease, MONDO:0044970; Leber optic atrophy, OMIM:535000; myoclonic epilepsy associated with ragged-red fibers, OMIM:545000; fatal infantile respiratory enzyme deficiency; Inherited Diabetes Mellitus; adult onset mild myopathy
Mitochondrial disorders v6.8 MT-TT Sarah Leigh reviewed gene: MT-TT: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Likely inborn error of metabolism v5.7 MT-TT Sarah Leigh reviewed gene: MT-TT: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MITOCHONDRIAL
Likely inborn error of metabolism v5.7 MT-TT Sarah Leigh Phenotypes for gene: MT-TT were changed from mitochondrial disease; Leber optic atrophy, OMIM:535000; myoclonic epilepsy associated with ragged-red fibers, OMIM:545000; fatal infantile respiratory enzyme deficiency; Inherited Diabetes Mellitus; adult onset mild mypathy to mitochondrial disease, MONDO:0044970; Leber optic atrophy, OMIM:535000; myoclonic epilepsy associated with ragged-red fibers, OMIM:545000; fatal infantile respiratory enzyme deficiency; Inherited Diabetes Mellitus; adult onset mild mypathy
Mitochondrial disorders v6.8 MT-TT Sarah Leigh Phenotypes for gene: MT-TT were changed from mitochondrial disease; Leber optic atrophy, OMIM:535000; myoclonic epilepsy associated with ragged-red fibers, OMIM:545000; fatal infantile respiratory enzyme deficiency; Inherited Diabetes Mellitus; adult onset mild mypathy to mitochondrial disease, MONDO:0044970; Leber optic atrophy, OMIM:535000; myoclonic epilepsy associated with ragged-red fibers, OMIM:545000; fatal infantile respiratory enzyme deficiency; Inherited Diabetes Mellitus; adult onset mild mypathy
Mitochondrial disorders v6.7 MT-TT Sarah Leigh Publications for gene: MT-TT were set to 32083134; 8769114; 9367299; 1645537; 8511015; 22638997; 29760464; 30236074; 28187756; 35808913
Intellectual disability v6.26 FAM177A1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v6.26 FAM177A1 Achchuthan Shanmugasundram Classified gene: FAM177A1 as Amber List (moderate evidence)
Intellectual disability v6.26 FAM177A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (four unrelated cases) for the promotion of this gene to green rating in the next GMS update.
Intellectual disability v6.26 FAM177A1 Achchuthan Shanmugasundram Gene: fam177a1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v6.26 FAM177A1 Achchuthan Shanmugasundram Classified gene: FAM177A1 as Amber List (moderate evidence)
Intellectual disability v6.26 FAM177A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (four unrelated cases) for the promotion of this gene to green rating in the next GMS update.
Intellectual disability v6.26 FAM177A1 Achchuthan Shanmugasundram Gene: fam177a1 has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v6.6 MT-TT Sarah Leigh Phenotypes for gene: MT-TT were changed from to mitochondrial disease; Leber optic atrophy, OMIM:535000; myoclonic epilepsy associated with ragged-red fibers, OMIM:545000; fatal infantile respiratory enzyme deficiency; Inherited Diabetes Mellitus; adult onset mild mypathy
Likely inborn error of metabolism v5.6 MT-TT Sarah Leigh Phenotypes for gene: MT-TT were changed from to mitochondrial disease; Leber optic atrophy, OMIM:535000; myoclonic epilepsy associated with ragged-red fibers, OMIM:545000; fatal infantile respiratory enzyme deficiency; Inherited Diabetes Mellitus; adult onset mild mypathy
Childhood onset dystonia, chorea or related movement disorder v4.4 MT-TT Sarah Leigh Phenotypes for gene: MT-TT were changed from to mitochondrial disease; Leber optic atrophy, OMIM:535000; myoclonic epilepsy associated with ragged-red fibers, OMIM:545000; fatal infantile respiratory enzyme deficiency; Inherited Diabetes Mellitus; adult onset mild mypathy
Intellectual disability v6.25 FAM177A1 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: FAM177A1.
Intellectual disability v6.25 FAM177A1 Achchuthan Shanmugasundram gene: FAM177A1 was added
gene: FAM177A1 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: FAM177A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAM177A1 were set to 25558065; 38767059
Phenotypes for gene: FAM177A1 were set to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Review for gene: FAM177A1 was set to GREEN
Added comment: PMID:25558065 reported a study of 143 multiplex consanguineous families, on which a homozygous frameshift variant in FAM177A1 gene was identified in a family with four affected siblings with intellectual disability, dolicocephaly, obesity, and macrocephaly. The variant segregated with all 4 affected siblings and parents were confirmed heterozygous carriers.

PMID:38767059 reported five individuals from three unrelated families with biallelic loss of function variants in FAM177A1 gene. They presented with clinical manifestations including global developmental delay, intellectual disability, seizures, behavioural abnormalities, hypotonia, gait disturbance, and macrocephaly.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Retinal disorders v5.11 THRB Achchuthan Shanmugasundram Classified gene: THRB as Amber List (moderate evidence)
Retinal disorders v5.11 THRB Achchuthan Shanmugasundram Added comment: Comment on list classification: Although there are three unrelated cases, all of them were identified with the same variant and this variant has not yet been functionally characterised. Hence, this gene should be rated amber with current evidence.

The 'watchlist' tag has also been added.
Retinal disorders v5.11 THRB Achchuthan Shanmugasundram Gene: thrb has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v6.5 MT-TT Sarah Leigh Publications for gene: MT-TT were set to
Likely inborn error of metabolism v5.5 MT-TT Sarah Leigh Publications for gene: MT-TT were set to
Retinal disorders v5.10 THRB Achchuthan Shanmugasundram Tag watchlist tag was added to gene: THRB.
Retinal disorders v5.10 THRB Achchuthan Shanmugasundram gene: THRB was added
gene: THRB was added to Retinal disorders. Sources: Literature
Mode of inheritance for gene: THRB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: THRB were set to 37547476
Phenotypes for gene: THRB were set to inherited retinal dystrophy, MONDO:0019118
Review for gene: THRB was set to AMBER
Added comment: PMID:37547476 reported a family of Spanish decent with autosomal dominant inherited retinal dystrophy (IRD) and monoallelic THRB variant (c.283 + 1G>A). An expanded genetic analysis of the THRB gene in an unsolved IRD cohort also resulted in the identification of the same variant in two additional unrelated families. There are also several studies that have shown a role for THRB gene in cone development in a wide range of model organisms.
Sources: Literature
Retinal disorders v5.9 SUMF1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Siying Lin and published in PMID:38863195, there are three unrelated cases with biallelic SUMF1 variants and non-syndromic retinal dystrophy. Hence, this gene can be promoted to green rating in the next GMS update.; to: Comment on list classification: As reviewed by Siying Lin and published in PMID:38863195, there are three unrelated cases with biallelic SUMF1 variants and retinal dystrophy. Hence, this gene can be promoted to green rating in the next GMS update.
Retinal disorders v5.9 SUMF1 Achchuthan Shanmugasundram Classified gene: SUMF1 as Amber List (moderate evidence)
Retinal disorders v5.9 SUMF1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Siying Lin and published in PMID:38863195, there are three unrelated cases with biallelic SUMF1 variants and non-syndromic retinal dystrophy. Hence, this gene can be promoted to green rating in the next GMS update.
Retinal disorders v5.9 SUMF1 Achchuthan Shanmugasundram Gene: sumf1 has been classified as Amber List (Moderate Evidence).
Retinal disorders v5.8 SUMF1 Achchuthan Shanmugasundram Phenotypes for gene: SUMF1 were changed from Retinal dystrophy to Multiple sulfatase deficiency, OMIM:272200; inherited retinal dystrophy, MONDO:0019118
Retinal disorders v5.7 SUMF1 Achchuthan Shanmugasundram Publications for gene: SUMF1 were set to PMID 38863195
Retinal disorders v5.6 SUMF1 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: SUMF1.
Tag Q2_24_NHS_review tag was added to gene: SUMF1.
Retinal disorders v5.6 SUMF1 Achchuthan Shanmugasundram reviewed gene: SUMF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 38863195; Phenotypes: Multiple sulfatase deficiency, OMIM:272200, inherited retinal dystrophy, MONDO:0019118; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
DDG2P v4.5 AFF2 Sarah Leigh Publications for gene: AFF2 were set to 8334699; 21739600
Intellectual disability v6.24 AFF2 Sarah Leigh Publications for gene: AFF2 were set to 21739600; 8334699; 25529582; 24896178
DDG2P v4.4 AFF2 Sarah Leigh Tag nucleotide-repeat-expansion tag was added to gene: AFF2.
DDG2P v4.4 AFF2 Sarah Leigh reviewed gene: AFF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 8334699, 8023854, 21739600, 9299237, 11171404, 11923441, 19136466, 2356291; Phenotypes: ; Mode of inheritance: None
Intellectual disability v6.23 AFF2 Sarah Leigh reviewed gene: AFF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 8334699, 8023854, 21739600, 9299237, 11171404, 11923441, 19136466, 2356291; Phenotypes: ; Mode of inheritance: None
Intellectual disability v6.23 AFF2 Sarah Leigh Phenotypes for gene: AFF2 were changed from Intellectual developmental disorder, X-linked 109, OMIM:309548; Fragile XE syndrome (FRAXE) to Intellectual developmental disorder, X-linked 109, OMIM:309548; FRAXE intellectual disability, MONDO:0010659
DDG2P v4.4 AFF2 Sarah Leigh Phenotypes for gene: AFF2 were changed from FRAGILE X-E MENTAL RETARDATION SYNDROME 309548 to Intellectual developmental disorder, X-linked 109, OMIM:309548; FRAXE intellectual disability, MONDO:0010659
Intellectual disability v6.22 AFF2 Sarah Leigh Publications for gene: AFF2 were set to 21739600; 8334699
Intellectual disability v6.22 AFF2 Sarah Leigh Publications for gene: AFF2 were set to
Lipodystrophy - childhood onset v4.54 WRN Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE tag was added to gene: WRN.
Lipodystrophy - childhood onset v4.54 PSMB8 Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE tag was added to gene: PSMB8.
Lipodystrophy - childhood onset v4.54 PSMB4 Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE tag was added to gene: PSMB4.
Lipodystrophy - childhood onset v4.54 POC1A Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE tag was added to gene: POC1A.
Lipodystrophy - childhood onset v4.54 PIK3R1 Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE tag was added to gene: PIK3R1.
Lipodystrophy - childhood onset v4.54 PCYT1A Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE tag was added to gene: PCYT1A.
Lipodystrophy - childhood onset v4.54 PCNT Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE tag was added to gene: PCNT.
Lipodystrophy - childhood onset v4.54 MFN2 Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE tag was added to gene: MFN2.
Lipodystrophy - childhood onset v4.54 EPHX1 Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE tag was added to gene: EPHX1.
Lipodystrophy - childhood onset v4.54 BLM Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE tag was added to gene: BLM.
Lipodystrophy - childhood onset v4.54 ALMS1 Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE tag was added to gene: ALMS1.
Ocular coloboma v1.49 GDF3 Arina Puzriakova Publications for gene: GDF3 were set to
Ocular coloboma v1.48 GDF3 Arina Puzriakova Mode of inheritance for gene: GDF3 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v5.6 GDF3 Arina Puzriakova Mode of inheritance for gene: GDF3 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Anophthalmia or microphthalmia v1.52 GDF3 Arina Puzriakova Mode of inheritance for gene: GDF3 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Skeletal dysplasia v5.5 GDF3 Arina Puzriakova Publications for gene: GDF3 were set to 19864492
Lipodystrophy - childhood onset v4.54 WRN Achchuthan Shanmugasundram Deleted their comment
Lipodystrophy - childhood onset v4.54 PSMB8 Achchuthan Shanmugasundram Deleted their comment
Lipodystrophy - childhood onset v4.54 PSMB4 Achchuthan Shanmugasundram Deleted their comment
Lipodystrophy - childhood onset v4.54 POC1A Achchuthan Shanmugasundram Deleted their comment
Lipodystrophy - childhood onset v4.54 PIK3R1 Achchuthan Shanmugasundram Deleted their comment
Lipodystrophy - childhood onset v4.54 PCYT1A Achchuthan Shanmugasundram Deleted their comment
Skeletal dysplasia v5.4 GDF3 Arina Puzriakova commented on gene: GDF3
Lipodystrophy - childhood onset v4.54 PCNT Achchuthan Shanmugasundram Deleted their comment
Lipodystrophy - childhood onset v4.54 MFN2 Achchuthan Shanmugasundram Deleted their comment
Lipodystrophy - childhood onset v4.54 EPHX1 Achchuthan Shanmugasundram Deleted their comment
Lipodystrophy - childhood onset v4.54 BLM Achchuthan Shanmugasundram Deleted their comment
Lipodystrophy - childhood onset v4.54 ALMS1 Achchuthan Shanmugasundram Deleted their comment
Lipodystrophy - childhood onset v4.54 WRN Achchuthan Shanmugasundram commented on gene: WRN: This gene is approved to upgrade to Green when TD eligibility and Clinical Indication name is expanded to Severe insulin resistance and lipodystrophy syndromes.
Lipodystrophy - childhood onset v4.54 PSMB8 Achchuthan Shanmugasundram commented on gene: PSMB8: This gene is approved to upgrade to Green when TD eligibility and Clinical Indication name is expanded to Severe insulin resistance and lipodystrophy syndromes.
Lipodystrophy - childhood onset v4.54 PSMB4 Achchuthan Shanmugasundram commented on gene: PSMB4: This gene is approved to upgrade to Green when TD eligibility and Clinical Indication name is expanded to Severe insulin resistance and lipodystrophy syndromes.
Lipodystrophy - childhood onset v4.54 POC1A Achchuthan Shanmugasundram commented on gene: POC1A: This gene is approved to upgrade to Green when TD eligibility and Clinical Indication name is expanded to Severe insulin resistance and lipodystrophy syndromes.
Lipodystrophy - childhood onset v4.54 PIK3R1 Achchuthan Shanmugasundram commented on gene: PIK3R1: This gene is approved to upgrade to Green when TD eligibility and Clinical Indication name is expanded to Severe insulin resistance and lipodystrophy syndromes.
Lipodystrophy - childhood onset v4.54 PCYT1A Achchuthan Shanmugasundram commented on gene: PCYT1A: This gene is approved to upgrade to Green when TD eligibility and Clinical Indication name is expanded to Severe insulin resistance and lipodystrophy syndromes.
Lipodystrophy - childhood onset v4.54 PCNT Achchuthan Shanmugasundram commented on gene: PCNT: This gene is approved to upgrade to Green when TD eligibility and Clinical Indication name is expanded to Severe insulin resistance and lipodystrophy syndromes.
Lipodystrophy - childhood onset v4.54 MFN2 Achchuthan Shanmugasundram commented on gene: MFN2: This gene is approved to upgrade to Green when TD eligibility and Clinical Indication name is expanded to Severe insulin resistance and lipodystrophy syndromes.
Lipodystrophy - childhood onset v4.54 EPHX1 Achchuthan Shanmugasundram commented on gene: EPHX1: This gene is approved to upgrade to Green when TD eligibility and Clinical Indication name is expanded to Severe insulin resistance and lipodystrophy syndromes.
Lipodystrophy - childhood onset v4.54 BLM Achchuthan Shanmugasundram commented on gene: BLM: This gene is approved to upgrade to Green when TD eligibility and Clinical Indication name is expanded to Severe insulin resistance and lipodystrophy syndromes.
Lipodystrophy - childhood onset v4.54 ALMS1 Achchuthan Shanmugasundram commented on gene: ALMS1: This gene is approved to upgrade to Green when TD eligibility and Clinical Indication name is expanded to Severe insulin resistance and lipodystrophy syndromes.
Lipodystrophy - childhood onset v4.53 WRN Achchuthan Shanmugasundram Source Expert Review Amber was added to WRN.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Lipodystrophy - childhood onset v4.53 PSMB8 Achchuthan Shanmugasundram Source Expert Review Amber was added to PSMB8.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Lipodystrophy - childhood onset v4.53 PSMB4 Achchuthan Shanmugasundram Source Expert Review Amber was added to PSMB4.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Lipodystrophy - childhood onset v4.53 POC1A Achchuthan Shanmugasundram Source Expert Review Amber was added to POC1A.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Lipodystrophy - childhood onset v4.53 PIK3R1 Achchuthan Shanmugasundram Source Expert Review Amber was added to PIK3R1.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Lipodystrophy - childhood onset v4.53 PCYT1A Achchuthan Shanmugasundram Source Expert Review Amber was added to PCYT1A.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Lipodystrophy - childhood onset v4.53 PCNT Achchuthan Shanmugasundram Source Expert Review Amber was added to PCNT.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Lipodystrophy - childhood onset v4.53 MFN2 Achchuthan Shanmugasundram Source Expert Review Amber was added to MFN2.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Lipodystrophy - childhood onset v4.53 EPHX1 Achchuthan Shanmugasundram Source Expert Review Amber was added to EPHX1.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Lipodystrophy - childhood onset v4.53 BLM Achchuthan Shanmugasundram Source Expert Review Amber was added to BLM.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Lipodystrophy - childhood onset v4.53 ALMS1 Achchuthan Shanmugasundram Source Expert Review Amber was added to ALMS1.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Cerebral vascular malformations v3.16 CBS Ginat Narkis gene: CBS was added
gene: CBS was added to Cerebral vascular malformations. Sources: Literature
Mode of inheritance for gene: CBS was set to BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v4.3 GNB2 Sarah Graham gene: GNB2 was added
gene: GNB2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: GNB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GNB2 were set to 36658419
Mode of pathogenicity for gene: GNB2 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: GNB2 was set to GREEN
Added comment: Gene associated with autosomal dominant neurodevelopmental disorder; features include dysmorphic facial features, cardiac and renal abnormalities (OMIM #619503). Recurrent de novo pathogenic missense variant p.(Lys89Glu) (https://www.ncbi.nlm.nih.gov/clinvar/variation/1217306/) reported in a fetus with phenotype consistent with this gene: cardiac abnormalities (hypoplastic left heart and hypoplastic aortic arch, double outlet right ventricle, great arteries located side-by-side, ventricular septal defect, persistent left superior vena cava connecting to coronary sinus), renal agenesis, mildly dysmorphic facies (Byrne 2023 PMID: 36658419).
Sources: Literature
Fetal anomalies v4.3 KCNT1 Sarah Graham reviewed gene: KCNT1: Rating: AMBER; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 36307859; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v4.3 CLCN5 Sarah Graham gene: CLCN5 was added
gene: CLCN5 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: CLCN5 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: CLCN5 were set to 36307859; 36495297; 37229200
Review for gene: CLCN5 was set to RED
Added comment: Loss-of-function variants associated with X-linked recessive renal tubular disorders. Maternally inherited hemizygous splice variant, c.934-1G>T, reported in 3 male fetuses with variable phenotypes across 3 studies from the same centre. Phenotypes in reported cases: polyhydramnios and large size for gestational age (Fu 2022 PMID: 36307859, case 229); growth restriction, polyhydramnios, pre-term birth at 31 weeks (Zhou 2023 PMID: 36495297, patient 5); microcephaly (Wang 2023 PMID: 37229200, patient 18). No definitive evidence that this variant is pathogenic. As all prenatal reports are of the same variant and from the same centre, concern that these may be incidental findings due to variant frequency in the local population (variant absent from gnomAD).
Sources: Literature
Fetal anomalies v4.3 ARV1 Sarah Graham gene: ARV1 was added
gene: ARV1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ARV1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARV1 were set to PMID: 36307859; 34296759
Review for gene: ARV1 was set to AMBER
Added comment: Biallelic loss-of-function variants associated with autosomal recessive developmental and epileptic encephalopathy-38 (DEE38). Biallelic variants reported prenatally in 3 families (4 fetuses) in association with abnormal scan findings, particularly renal abnormalities. Renal abnormalities are not a common postnatal finding in this disorder, so causal relationship to scan findings is unclear.

Salian 2021 PMID: 34296759, patient 3 - compound heterozygous frameshift and missense variants, p.(Pro174Alafs*14) and p.(Cys34Tyr), with prenatal hydronephrosis, postnatally profound ID, seizures, genitourinary abnormalities. Salian 2021 PMID: 34296759, Patients 5/6 (successive pregnancies of consanguineous parents) - homozygous c.674-1G>A; patient 5 termination at week 22 due to megaureter, small femora and humeri and narrow thorax; patient 6 NT 6.3 mm at week 14, bilaterally dilated renal pelvis at week 16+1. Fu 2022 PMID: 36307859 - compound het frameshift variants, p.(Glu137Asnfs*13) and p.(Pro174Alafs*14), reported in a fetus with dilation of lateral ventricles and polyhydramnios.
Sources: Literature
Fetal anomalies v4.3 KCNK9 Sarah Graham gene: KCNK9 was added
gene: KCNK9 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: KCNK9 was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Publications for gene: KCNK9 were set to PMID: 36307859
Review for gene: KCNK9 was set to GREEN
Added comment: The recurrent p.(Gly236Arg) variant is well established as the cause of KCNK9 Imprinting Syndrome / Birk-Barel Syndrome (OMIM #612292) when present on the maternal allele. This variant has been reported as a de novo finding on exome sequencing in a fetus with scan findings consistent with this disorder (micrognathia, cleft palate). PMID: 36307859
Sources: Literature
Retinal disorders v5.6 SUMF1 Siying Lin gene: SUMF1 was added
gene: SUMF1 was added to Retinal disorders. Sources: Literature
Mode of inheritance for gene: SUMF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUMF1 were set to PMID 38863195
Phenotypes for gene: SUMF1 were set to Retinal dystrophy
Mode of pathogenicity for gene: SUMF1 was set to Other
Review for gene: SUMF1 was set to GREEN
Added comment: 3 cases published in literature with biallelic variants in SUMF1 and retinal dystrophy, one paediatric patient had an attenuated phenotype, the other two adult patients had non-syndromic retinal dystrophy.

Retinal dystrophy is part of the multiple sulfatase deficiency phenotype typically associated with biallelic variants in SUMF1, and these cases show that presumed hypomorphic variants in SUMF1 may also be associated with non-syndromic retinal dystrophy
Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 IL1R1 Dmitrijs Rots gene: IL1R1 was added
gene: IL1R1 was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: IL1R1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IL1R1 were set to PMID: 37315560
Phenotypes for gene: IL1R1 were set to chronic recurrent multifocal osteomyelitis
Penetrance for gene: IL1R1 were set to unknown
Mode of pathogenicity for gene: IL1R1 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: IL1R1 was set to AMBER
Added comment: PMID: 37315560 reported a patient with a de novo missense variant in IL1R1 with functional evidence. Should be amber till further cases?
Sources: Literature
Undiagnosed metabolic disorders v1.620 SLC6A19 Achchuthan Shanmugasundram Mode of inheritance for gene: SLC6A19 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Undiagnosed metabolic disorders v1.619 SLC6A19 Achchuthan Shanmugasundram Tag Q2_24_MOI was removed from gene: SLC6A19.
Tag Q2_24_expert_review was removed from gene: SLC6A19.
Undiagnosed metabolic disorders v1.619 SLC6A19 Achchuthan Shanmugasundram changed review comment from: Comment on mode of inheritance: As reviewed by Tracy Lester, SLC6A19 is associated with Hartnup disorder (MIM #234500), which is caused by biallelic variants. SLC6A19 is currently associated with Hyperglycinuria (MIM #138500) and Iminoglycinuria (MIM #242600) in both PanelApp and PanelApp Australia and hence the MOI was set to both monoallelic and biallelic. However, these phenotypes are caused by SLC36A2.

The association in PanelApp was due to the speculation in PMID:19033659 that combination of variants in SLC36A2 with variants in SLC6A20 or SLC6A19 may have contributed to these phenotypes in three of the reported families. The identified variant from SLC6A19 has now been classified as polymorphism because it was present in 62,195 of 282,492 alleles and in 7,227 homozygotes in the gnomAD database (v2.1.1), for an allele frequency of 0.2202 (https://www.omim.org/entry/608893?search=slc6a19&highlight=slc6a19#allelicVariants).

Hence, the MOI should be updated to 'BIALLELIC, autosomal or pseudoautosomal' in the next GMS update.; to: Comment on mode of inheritance: As reviewed by Tracy Lester, SLC6A19 is associated with Hartnup disorder (MIM #234500), which is caused by biallelic variants. SLC6A19 is currently associated with Hyperglycinuria (MIM #138500) and Iminoglycinuria (MIM #242600) in both PanelApp and PanelApp Australia and hence the MOI was set to both monoallelic and biallelic. However, these phenotypes are caused by SLC36A2.

The association in PanelApp was due to the speculation in PMID:19033659 that combination of variants in SLC36A2 with variants in SLC6A20 or SLC6A19 may have contributed to these phenotypes in three of the reported families. The identified variant from SLC6A19 has now been classified as polymorphism because it was present in 62,195 of 282,492 alleles and in 7,227 homozygotes in the gnomAD database (v2.1.1), for an allele frequency of 0.2202 (https://www.omim.org/entry/608893?search=slc6a19&highlight=slc6a19#allelicVariants).

Hence, the MOI should be updated to 'BIALLELIC, autosomal or pseudoautosomal' in this panel.
Likely inborn error of metabolism v5.4 SLC6A19 Achchuthan Shanmugasundram Phenotypes for gene: SLC6A19 were changed from Hartnup disorder, OMIM:234500 to Hartnup disorder, OMIM:234500
Undiagnosed metabolic disorders v1.619 SLC6A19 Achchuthan Shanmugasundram Tag Q2_24_NHS_review was removed from gene: SLC6A19.
Likely inborn error of metabolism v5.5 SLC6A19 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: As reviewed by Tracy Lester, SLC6A19 is associated with Hartnup disorder (MIM #234500), which is caused by biallelic variants. SLC6A19 is currently associated with Hyperglycinuria (MIM #138500) and Iminoglycinuria (MIM #242600) in both PanelApp and PanelApp Australia and hence the MOI was set to both monoallelic and biallelic. However, these phenotypes are caused by SLC36A2.

The association in PanelApp was due to the speculation in PMID:19033659 that combination of variants in SLC36A2 with variants in SLC6A20 or SLC6A19 may have contributed to these phenotypes in three of the reported families. The identified variant from SLC6A19 has now been classified as polymorphism because it was present in 62,195 of 282,492 alleles and in 7,227 homozygotes in the gnomAD database (v2.1.1), for an allele frequency of 0.2202 (https://www.omim.org/entry/608893?search=slc6a19&highlight=slc6a19#allelicVariants)nts).

Hence, the MOI should be updated to 'BIALLELIC, autosomal or pseudoautosomal' in the next GMS update.
Likely inborn error of metabolism v5.5 SLC6A19 Achchuthan Shanmugasundram Mode of inheritance for gene: SLC6A19 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Likely inborn error of metabolism v5.4 SLC6A19 Achchuthan Shanmugasundram Phenotypes for gene: SLC6A19 were changed from Hartnup disorder, OMIM:234500 to Hartnup disorder, OMIM:234500
Likely inborn error of metabolism v5.4 SLC6A19 Achchuthan Shanmugasundram Phenotypes for gene: SLC6A19 were changed from Hartnup disorder, OMIM:234500 to Hartnup disorder, OMIM:234500
Likely inborn error of metabolism v5.4 SLC6A19 Achchuthan Shanmugasundram Phenotypes for gene: SLC6A19 were changed from Iminoglycinuria, digenic; Hartnup disorder AD to Hartnup disorder, OMIM:234500
Likely inborn error of metabolism v5.3 SLC6A19 Achchuthan Shanmugasundram Tag Q2_24_NHS_review tag was added to gene: SLC6A19.
Likely inborn error of metabolism v5.3 SLC6A19 Achchuthan Shanmugasundram Tag Q2_24_MOI tag was added to gene: SLC6A19.
Tag Q2_24_expert_review tag was added to gene: SLC6A19.
Likely inborn error of metabolism v5.3 SLC6A19 Achchuthan Shanmugasundram reviewed gene: SLC6A19: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hartnup disorder, OMIM:234500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Undiagnosed metabolic disorders v1.619 SLC6A19 Achchuthan Shanmugasundram Tag Q2_24_expert_review tag was added to gene: SLC6A19.
Tag Q2_24_NHS_review tag was added to gene: SLC6A19.
Undiagnosed metabolic disorders v1.619 SLC6A19 Achchuthan Shanmugasundram Tag Q2_24_MOI tag was added to gene: SLC6A19.
Undiagnosed metabolic disorders v1.619 SLC6A19 Achchuthan Shanmugasundram Phenotypes for gene: SLC6A19 were changed from Hartnup disorder 234500 AR; Hyperglycinuria 138500 AD; Iminoglycinuria, digenic 242600 AR to Hartnup disorder, OMIM:234500
Undiagnosed metabolic disorders v1.618 SLC6A19 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: As reviewed by Tracy Lester, SLC6A19 is associated with Hartnup disorder (MIM #234500), which is caused by biallelic variants. SLC6A19 is currently associated with Hyperglycinuria (MIM #138500) and Iminoglycinuria (MIM #242600) in both PanelApp and PanelApp Australia and hence the MOI was set to both monoallelic and biallelic. However, these phenotypes are caused by SLC36A2.

The association in PanelApp was due to the speculation in PMID:19033659 that combination of variants in SLC36A2 with variants in SLC6A20 or SLC6A19 may have contributed to these phenotypes in three of the reported families. The identified variant from SLC6A19 has now been classified as polymorphism because it was present in 62,195 of 282,492 alleles and in 7,227 homozygotes in the gnomAD database (v2.1.1), for an allele frequency of 0.2202 (https://www.omim.org/entry/608893?search=slc6a19&highlight=slc6a19#allelicVariants).

Hence, the MOI should be updated to 'BIALLELIC, autosomal or pseudoautosomal' in the next GMS update.
Undiagnosed metabolic disorders v1.618 SLC6A19 Achchuthan Shanmugasundram Mode of inheritance for gene: SLC6A19 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Undiagnosed metabolic disorders v1.617 SLC6A19 Achchuthan Shanmugasundram reviewed gene: SLC6A19: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hartnup disorder, OMIM:234500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v5.6 TANGO2 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Asma Hamad, biallelic TANGO2 variants are associated with a syndromic disorder characterized by neurodevelopmental delays, seizures, intermittent ataxia, hypothyroidism and life-threatening metabolic and cardiac crises. Hence, there is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.; to: Comment on list classification: As reviewed by Asma Hamad, biallelic TANGO2 variants are associated with a syndromic disorder characterized by neurodevelopmental delays, seizures, intermittent ataxia, hypothyroidism and life-threatening metabolic and cardiac crises.

Hence, there is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.
Ataxia and cerebellar anomalies - narrow panel v5.6 TANGO2 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Asma Hamad, biallelic TANGO2 variants are associated with a syndromic disorder comprising characterized by neurodevelopmental delays, seizures, intermittent ataxia, hypothyroidism and life-threatening metabolic and cardiac crises. Hence, there is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.; to: Comment on list classification: As reviewed by Asma Hamad, biallelic TANGO2 variants are associated with a syndromic disorder characterized by neurodevelopmental delays, seizures, intermittent ataxia, hypothyroidism and life-threatening metabolic and cardiac crises. Hence, there is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.
Ataxia and cerebellar anomalies - narrow panel v5.6 TANGO2 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: TANGO2.
Tag Q2_24_NHS_review tag was added to gene: TANGO2.
Ataxia and cerebellar anomalies - narrow panel v5.6 TANGO2 Achchuthan Shanmugasundram Classified gene: TANGO2 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v5.6 TANGO2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Asma Hamad, biallelic TANGO2 variants are associated with a syndromic disorder comprising characterized by neurodevelopmental delays, seizures, intermittent ataxia, hypothyroidism and life-threatening metabolic and cardiac crises. Hence, there is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.
Ataxia and cerebellar anomalies - narrow panel v5.6 TANGO2 Achchuthan Shanmugasundram Gene: tango2 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v5.5 TANGO2 Achchuthan Shanmugasundram Publications for gene: TANGO2 were set to
Ataxia and cerebellar anomalies - narrow panel v5.4 TANGO2 Achchuthan Shanmugasundram Phenotypes for gene: TANGO2 were changed from to Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration, OMIM:616878
Ataxia and cerebellar anomalies - narrow panel v5.3 TANGO2 Achchuthan Shanmugasundram reviewed gene: TANGO2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30245509, 31276219, 32527145, 36473599; Phenotypes: Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration, OMIM:616878; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric or syndromic cardiomyopathy v4.7 NEXN Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: As reviewed by Hannah Robinson, there is sufficient evidence available for updating the MOI from 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' to 'BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal' in the next GMS update.
Paediatric or syndromic cardiomyopathy v4.7 NEXN Achchuthan Shanmugasundram Mode of inheritance for gene: NEXN was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Paediatric or syndromic cardiomyopathy v4.6 NEXN Achchuthan Shanmugasundram edited their review of gene: NEXN: Added comment: PMID:32058062 - One male foetus was reported with compound heterozygous NEXN variants (c.1756A > T & c.1909_1912del) and dilated cardiomyopathy.

PMID:33027564 - One case was identified with dilated and hypertrophic cardiomyopathy and with compound heterozygous NEXN variants (p.Arg216Ter & p.Lys536fs). However, it was not possible to determine the phase (whether cis or trans) on the basis of exome sequencing.

PMID:33949776 - One patient presented with fetal hydrops at 33  weeks gestation requiring emergency caesarian delivery. Postnatally she required ventilation and continuous inotropic support for left ventricle systolic dysfunction. She died after 2 weeks when therapy was withdrawn. Homozygous c.1174C > T (p.Arg392Ter) variant in the NEXN gene was identified in this patient.

PMID:35166435 - A female from a four-generation Swedish family comprising 42 individuals had three three consecutive pregnancies with intrauterine fetal deaths caused by a lethal form of dilated cardiomyopathy. Homozygous NEXN variant (c.1302del/ p.Ile435Serfs*3) was identified in these foetuses.

In addition to these peer reviewed cases, additional biallelic cases were reported in the following reports: 10.1016/j.jsha.2013.03.180 & 10.1016/j.gimo.2023.100620.

The phenotypes associated with monoallelic variants are already reported in OMIM. However, phenotypes associated with biallelic variants are not yet reported either in OMIM or in Gene2Phenotype.; Changed publications to: 32058062, 33027564, 33949776, 35166435
Paediatric or syndromic cardiomyopathy v4.6 NEXN Achchuthan Shanmugasundram Tag Q2_24_NHS_review tag was added to gene: NEXN.
Paediatric or syndromic cardiomyopathy v4.6 NEXN Achchuthan Shanmugasundram Tag Q2_24_MOI tag was added to gene: NEXN.
Paediatric or syndromic cardiomyopathy v4.6 NEXN Achchuthan Shanmugasundram reviewed gene: NEXN: Rating: GREEN; Mode of pathogenicity: None; Publications: 32058062, 32058062, 35166435; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Intellectual disability v6.21 ITSN1 Achchuthan Shanmugasundram Classified gene: ITSN1 as Amber List (moderate evidence)
Intellectual disability v6.21 ITSN1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.
Intellectual disability v6.21 ITSN1 Achchuthan Shanmugasundram Gene: itsn1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v6.21 ITSN1 Achchuthan Shanmugasundram Classified gene: ITSN1 as Amber List (moderate evidence)
Intellectual disability v6.21 ITSN1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.
Intellectual disability v6.21 ITSN1 Achchuthan Shanmugasundram Gene: itsn1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v6.21 ITSN1 Achchuthan Shanmugasundram Classified gene: ITSN1 as Amber List (moderate evidence)
Intellectual disability v6.21 ITSN1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.
Intellectual disability v6.21 ITSN1 Achchuthan Shanmugasundram Gene: itsn1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v6.21 ITSN1 Achchuthan Shanmugasundram Classified gene: ITSN1 as Amber List (moderate evidence)
Intellectual disability v6.21 ITSN1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.
Intellectual disability v6.21 ITSN1 Achchuthan Shanmugasundram Gene: itsn1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v6.20 ITSN1 Achchuthan Shanmugasundram Phenotypes for gene: ITSN1 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v6.21 ITSN1 Achchuthan Shanmugasundram Classified gene: ITSN1 as Amber List (moderate evidence)
Intellectual disability v6.21 ITSN1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS update
Intellectual disability v6.21 ITSN1 Achchuthan Shanmugasundram Gene: itsn1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v6.20 ITSN1 Achchuthan Shanmugasundram Phenotypes for gene: ITSN1 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v6.20 ITSN1 Achchuthan Shanmugasundram Phenotypes for gene: ITSN1 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v6.20 ITSN1 Achchuthan Shanmugasundram Phenotypes for gene: ITSN1 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v6.20 ITSN1 Achchuthan Shanmugasundram Phenotypes for gene: ITSN1 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v6.20 ITSN1 Achchuthan Shanmugasundram Phenotypes for gene: ITSN1 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v6.20 ITSN1 Achchuthan Shanmugasundram Phenotypes for gene: ITSN1 were changed from autism spectrum disorders; intellectual disability; epilepsy. to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v6.19 ITSN1 Achchuthan Shanmugasundram Publications for gene: ITSN1 were set to Bruel et al., 2021 (PMID: 34707297):
Intellectual disability v6.18 ITSN1 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: ITSN1.
Tag Q2_24_NHS_review tag was added to gene: ITSN1.
Intellectual disability v6.18 ITSN1 Achchuthan Shanmugasundram reviewed gene: ITSN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34707297; Phenotypes: neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Severe microcephaly v5.8 RNU4-2 Arina Puzriakova Entity copied from Intellectual disability v6.18
Severe microcephaly v5.8 RNU4-2 Arina Puzriakova gene: RNU4-2 was added
gene: RNU4-2 was added to Severe microcephaly. Sources: Expert Review Amber,Literature
locus-type-rna-small-nuclear, Q2_24_promote_green tags were added to gene: RNU4-2.
Mode of inheritance for gene: RNU4-2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RNU4-2 were set to 38821540; 38645094
Phenotypes for gene: RNU4-2 were set to Neurodevelopmental disorder, MONDO:0700092, RNU4-2 related
Early onset or syndromic epilepsy v5.14 RNU4-2 Arina Puzriakova Entity copied from Intellectual disability v6.18
Early onset or syndromic epilepsy v5.14 RNU4-2 Arina Puzriakova gene: RNU4-2 was added
gene: RNU4-2 was added to Early onset or syndromic epilepsy. Sources: Expert Review Amber,Literature
locus-type-rna-small-nuclear, Q2_24_promote_green tags were added to gene: RNU4-2.
Mode of inheritance for gene: RNU4-2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RNU4-2 were set to 38821540; 38645094
Phenotypes for gene: RNU4-2 were set to Neurodevelopmental disorder, MONDO:0700092, RNU4-2 related
Intellectual disability v6.18 RNU4-2 Arina Puzriakova Classified gene: RNU4-2 as Amber List (moderate evidence)
Intellectual disability v6.18 RNU4-2 Arina Puzriakova Added comment: Comment on list classification: The two papers (PMID: 38821540; 38645094) corroborate mutual findings and report over 100 unrelated individuals with a clinically overlapping neurological disorder and variants the non-coding gene RNU4-2.

Overall there is sufficient evidence to promote this gene to Green status at the next GMS panel update.
Intellectual disability v6.18 RNU4-2 Arina Puzriakova Gene: rnu4-2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v6.17 RNU4-2 Arina Puzriakova Tag locus-type-rna-small-nuclear tag was added to gene: RNU4-2.
Tag Q2_24_promote_green tag was added to gene: RNU4-2.
Intellectual disability v6.17 RNU4-2 Arina Puzriakova Publications for gene: RNU4-2 were set to 38645094
Intellectual disability v6.16 RNU4-2 Arina Puzriakova reviewed gene: RNU4-2: Rating: GREEN; Mode of pathogenicity: None; Publications: 38821540, 38645094; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Thoracic aortic aneurysm or dissection (GMS) v3.16 THBS2 Arina Puzriakova Publications for gene: THBS2 were set to https://doi.org/10.1038/s41431-024-01559-1
Thoracic aortic aneurysm or dissection (GMS) v3.15 THBS2 Arina Puzriakova Classified gene: THBS2 as Red List (low evidence)
Thoracic aortic aneurysm or dissection (GMS) v3.15 THBS2 Arina Puzriakova Added comment: Comment on list classification: New gene added by Neeti Ghali (NWTRGS). Rating Red as only a single family has been reported to date (see below) but this is a good candidate for future promotion if additional cases are identified.

- PMID: 38433265 (2024) reports on a three-generation family of Ashkenazi Jewish ancestry with a previously uncharacterised connective tissue disorder with features of EDS with prominent vascular involvement, caused by a heterozygous pathogenic variant (c.2686T>C, p.Cys896Arg) in THBS2.
Thoracic aortic aneurysm or dissection (GMS) v3.15 THBS2 Arina Puzriakova Gene: thbs2 has been classified as Red List (Low Evidence).
Ehlers Danlos syndrome with a likely monogenic cause v3.15 THBS2 Arina Puzriakova Classified gene: THBS2 as Red List (low evidence)
Ehlers Danlos syndrome with a likely monogenic cause v3.15 THBS2 Arina Puzriakova Gene: thbs2 has been classified as Red List (Low Evidence).
Ehlers Danlos syndrome with a likely monogenic cause v3.14 THBS2 Arina Puzriakova Publications for gene: THBS2 were set to https://doi.org/10.1038/s41431-024-01559-1
Ehlers Danlos syndrome with a likely monogenic cause v3.13 THBS2 Arina Puzriakova Classified gene: THBS2 as No list
Ehlers Danlos syndrome with a likely monogenic cause v3.13 THBS2 Arina Puzriakova Added comment: Comment on list classification: New gene added by Neeti Ghali (NWTRGS). Rating Red as only a single family has been reported to date (see below) but this is a good candidate for future promotion if additional cases are identified.

- PMID: 38433265 (2024) reports on a three-generation family of Ashkenazi Jewish ancestry with a previously uncharacterised connective tissue disorder with features of EDS with prominent vascular involvement, caused by a heterozygous pathogenic variant (c.2686T>C, p.Cys896Arg) in THBS2.
Ehlers Danlos syndrome with a likely monogenic cause v3.13 THBS2 Arina Puzriakova Gene: thbs2 has been removed from the panel.
Thoracic aortic aneurysm or dissection (GMS) v3.14 COL1A1 Arina Puzriakova changed review comment from: Comment on list classification: This gene was reassessed in light of the Green review by Neeti Ghali (NWTRGS). The evidence suggests that vascular complications are observed in a subset of cases. Colman et al. 2022 (PMID: 35587586) reviewed previously reported cases and show that 10/35 individuals presented with vascular phenotypes (4 artery dissection, 3 aneurysms (1 requiring embolisation), 2 aortic root dilation, 1 ascending aorta dilation, 3 arterial tortuosity).

In cases where vascular abnormalities are present, this panel may serve as an important diagnostic pathway, as highlighted by Neeti Ghali.

Upgrading from Red to Amber; however, due to conflicting expert reviews, this gene will be flagged for further GMS specialist assessment during the next iteration of GMS panel updates to determine if it should be made Green.; to: Comment on list classification: This gene was reassessed in light of the Green review by Neeti Ghali (NWTRGS). The evidence suggests that vascular complications can be observed in a subset of cases. Colman et al. 2022 (PMID: 35587586) reviewed previously reported cases and showed that 10/35 individuals presented with vascular phenotypes (4 artery dissection, 3 aneurysms (1 requiring embolisation), 2 aortic root dilation, 1 ascending aorta dilation, 3 arterial tortuosity).

In cases where vascular abnormalities are present, this panel may serve as an important diagnostic pathway, as highlighted by Neeti Ghali.

Upgrading from Red to Amber; however, due to conflicting expert reviews, this gene will be flagged for further GMS specialist assessment during the next iteration of GMS panel updates to determine if it should be made Green.
Thoracic aortic aneurysm or dissection (GMS) v3.14 COL1A1 Arina Puzriakova Tag Q2_24_expert_review tag was added to gene: COL1A1.
Thoracic aortic aneurysm or dissection (GMS) v3.14 COL1A1 Arina Puzriakova Classified gene: COL1A1 as Amber List (moderate evidence)
Thoracic aortic aneurysm or dissection (GMS) v3.14 COL1A1 Arina Puzriakova Added comment: Comment on list classification: This gene was reassessed in light of the Green review by Neeti Ghali (NWTRGS). The evidence suggests that vascular complications are observed in a subset of cases. Colman et al. 2022 (PMID: 35587586) reviewed previously reported cases and show that 10/35 individuals presented with vascular phenotypes (4 artery dissection, 3 aneurysms (1 requiring embolisation), 2 aortic root dilation, 1 ascending aorta dilation, 3 arterial tortuosity).

In cases where vascular abnormalities are present, this panel may serve as an important diagnostic pathway, as highlighted by Neeti Ghali.

Upgrading from Red to Amber; however, due to conflicting expert reviews, this gene will be flagged for further GMS specialist assessment during the next iteration of GMS panel updates to determine if it should be made Green.
Thoracic aortic aneurysm or dissection (GMS) v3.14 COL1A1 Arina Puzriakova Gene: col1a1 has been classified as Amber List (Moderate Evidence).
Thoracic aortic aneurysm or dissection (GMS) v3.13 COL1A1 Arina Puzriakova Phenotypes for gene: COL1A1 were changed from Ehlers-Danlos syndrome, classic, 130000; Ehlers-Danlos syndrome, type VIIA, 130060 to Ehlers-Danlos syndrome, arthrochalasia type, 1, OMIM:130060
Thoracic aortic aneurysm or dissection (GMS) v3.12 COL1A1 Arina Puzriakova Publications for gene: COL1A1 were set to
Thoracic aortic aneurysm or dissection (GMS) v3.11 COL1A1 Arina Puzriakova Tag Q2_24_promote_green tag was added to gene: COL1A1.
Tag Q2_24_NHS_review tag was added to gene: COL1A1.
Thoracic aortic aneurysm or dissection (GMS) v3.11 COL1A1 Neeti Ghali reviewed gene: COL1A1: Rating: GREEN; Mode of pathogenicity: Other; Publications: 35587586; Phenotypes: skin (soft, doughy, hyperextensible, fragile) with atrophic scarring, musculoskeletal (joint hypermobility, dislocations, spinal and chest wall deformities), vascular complications (see below); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ehlers Danlos syndrome with a likely monogenic cause v3.12 THBS2 Neeti Ghali gene: THBS2 was added
gene: THBS2 was added to Ehlers Danlos syndrome with a likely monogenic cause. Sources: Literature
Mode of inheritance for gene: THBS2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: THBS2 were set to https://doi.org/10.1038/s41431-024-01559-1
Phenotypes for gene: THBS2 were set to vascular phenotype; joint hypermobility, tendon rupture, joint dislocations; prolonged bleeding; atrophic scarring, aortopathy
Penetrance for gene: THBS2 were set to unknown
Mode of pathogenicity for gene: THBS2 was set to Other
Review for gene: THBS2 was set to AMBER
Added comment: For R101, I would consider this to be 'amber' (ie low-ish evidence at present). There is only one recently (March 2024) published family but mouse work was also described in this publication. The phenotype is described as a novel form of EDS with vascular features as well as musculoskeletal (joint hypermobility, tendon rupture and joint dislocations), haematological (prolonged bleeding) and dermatological features (atrophic scarring). One patient had cerebral aneurysms and died from an abdominal aorta dissection at the age of 70 (but therefore was not genetically confirmed) and one displayed an enlarged ascending aortic arch at 50 (4.2cm). Lifestyle factors were not discussed and the two younger relatives (30s) did not have aortopathy. Electron microscopy revealed abnormally disorganised collagen fibres. The variant described is a missense (Cys to Arg in highly conserved region) and a CRISPR/Cas9 knock-in mouse demonstrated phenotypic traits correlating with those observed in human subjects (but not aortopathy). Protein has been found to be mainly expressed in large blood vessels such as aorta.
Sources: Literature
Thoracic aortic aneurysm or dissection (GMS) v3.11 THBS2 Neeti Ghali gene: THBS2 was added
gene: THBS2 was added to Thoracic aortic aneurysm or dissection (GMS). Sources: Literature
Mode of inheritance for gene: THBS2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: THBS2 were set to https://doi.org/10.1038/s41431-024-01559-1
Phenotypes for gene: THBS2 were set to aortic dilatation and rupture; prolonged bleeding time; atrophic scarring, joint hypermobility and frequent joint dislocations
Penetrance for gene: THBS2 were set to unknown
Mode of pathogenicity for gene: THBS2 was set to Other
Review for gene: THBS2 was set to RED
Added comment: For R125, I would consider this to be 'red' (ie low evidence at present) but with a view to observing for other publications. There is only one recently (March 2024) published family but mouse work was also described in this publication. The phenotype is described as a novel form of EDS with vascular features as well as musculoskeletal (joint hypermobility, tendon rupture and joint dislocations), haematological (prolonged bleeding) and dermatological features (atrophic scarring). One patient had cerebral aneurysms and died from an abdominal aorta dissection at the age of 70 (but therefore was not genetically confirmed) and one displayed an enlarged ascending aortic arch at 50 (4.2cm). Lifestyle factors were not discussed and the two younger relatives (30s) did not have aortopathy. Electron microscopy revealed abnormally disorganised collagen fibres. The variant described is a missense (Cys to Arg in highly conserved region) and a CRISPR/Cas9 knock-in mouse demonstrated phenotypic traits correlating with those observed in human subjects (but not aortopathy). Protein has been found to be mainly expressed in large blood vessels such as aorta.
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v5.3 TANGO2 Asma Hamad changed review comment from: PMID 30245509
- Report of 14 individuals with TANGO2-related disorder. One of the patients discussed developed ataxia and dizziness at the age of 2 yeas (Patient 10)

PMID 31276219
- 2019 paper which reports 11 new cases of TANGO2-related disease. All 11 patients showed developmental delay with ataxia

PMID 36473599
- Data collected from 73 individuals studying the natural history of TANGO2 deficiency disorder. 94% of individuals (65/69) had ataxia as a feature. Ataxia was one of the symptoms found to occur between the ages of 1 to 3 years and of the first symptoms noted.

PMID 32527145
- Case report of a 6-year old girl diagnosed with TANGO2-related disease. By the age of 29 months, she had developed ataxia that worsened with viral illnesses and seizures and was recurrent in nature

I am a NHS Clinician and have clinical Experience of a patient who had episodic ataxia as one of their presenting features. Testing in the hereditary ataxia panel did not find any pathogenic variants as the TANGO2 gene is not present on the panel. A diagnosis was later achieved over 4 years later when it became evident they had learning difficulties and the R29 panel was activated.
Sources: Literature; to: PMID 30245509
- Report of 14 individuals with TANGO2-related disorder. One of the patients discussed developed ataxia and dizziness at the age of 2 yeas (Patient 10)

PMID 31276219
- 2019 paper which reports 11 new cases of TANGO2-related disease. All 11 patients showed developmental delay with ataxia

PMID 36473599
- Data collected from 73 individuals studying the natural history of TANGO2 deficiency disorder. 94% of individuals (65/69) had ataxia as a feature. Ataxia was one of the symptoms found to occur between the ages of 1 to 3 years and of the first symptoms noted.

PMID 32527145
- Case report of a 6-year old girl diagnosed with TANGO2-related disease. By the age of 29 months, she had developed ataxia that worsened with viral illnesses and seizures and was recurrent in nature

I am a NHS Clinician and have clinical experience of a patient who had episodic ataxia as one of their presenting features. Testing in the hereditary ataxia panel did not find any pathogenic variants as the TANGO2 gene was not present on the panel. A diagnosis was later achieved over 4 years later when it became evident they had learning difficulties and the R29 panel was activated.
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v5.3 TANGO2 Asma Hamad changed review comment from: PMID 30245509
- Report of 14 individuals with TANGO2-related disorder. One of the patients discussed developed ataxia and dizziness at the age of 2 yeas (Patient 10)

PMID 31276219
- 2019 paper which reports 11 new cases of TANGO2-related disease. All 11 patients showed developmental delay with ataxia

PMID 36473599
- Data collected from 73 individuals studying the natural history of TANGO2 deficiency disorder. 94% of individuals (65/69) had ataxia as a feature. Ataxia was one of the symptoms found to occur between the ages of 1 to 3 years and of the first symptoms noted.

PMID 32527145
- Case report of a 6-year old girl diagnosed with TANGO2-related disease. By the age of 29 months, she had developed ataxia that worsened with viral illnesses and seizures and was recurrent in nature

Clinical Experience of a patient who had episodic ataxia as one of their presenting features. Testing in the hereditary ataxia panel did not find any pathogenic variants as the TANGO2 gene is not present on the panel. A diagnosis was later achieved over 4 years later when it became evident they had learning difficulties and the R29 panel was activated.
Sources: Literature; to: PMID 30245509
- Report of 14 individuals with TANGO2-related disorder. One of the patients discussed developed ataxia and dizziness at the age of 2 yeas (Patient 10)

PMID 31276219
- 2019 paper which reports 11 new cases of TANGO2-related disease. All 11 patients showed developmental delay with ataxia

PMID 36473599
- Data collected from 73 individuals studying the natural history of TANGO2 deficiency disorder. 94% of individuals (65/69) had ataxia as a feature. Ataxia was one of the symptoms found to occur between the ages of 1 to 3 years and of the first symptoms noted.

PMID 32527145
- Case report of a 6-year old girl diagnosed with TANGO2-related disease. By the age of 29 months, she had developed ataxia that worsened with viral illnesses and seizures and was recurrent in nature

I am a NHS Clinician and have clinical Experience of a patient who had episodic ataxia as one of their presenting features. Testing in the hereditary ataxia panel did not find any pathogenic variants as the TANGO2 gene is not present on the panel. A diagnosis was later achieved over 4 years later when it became evident they had learning difficulties and the R29 panel was activated.
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v5.3 TANGO2 Asma Hamad gene: TANGO2 was added
gene: TANGO2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: TANGO2 was set to BIALLELIC, autosomal or pseudoautosomal
Review for gene: TANGO2 was set to AMBER
Added comment: PMID 30245509
- Report of 14 individuals with TANGO2-related disorder. One of the patients discussed developed ataxia and dizziness at the age of 2 yeas (Patient 10)

PMID 31276219
- 2019 paper which reports 11 new cases of TANGO2-related disease. All 11 patients showed developmental delay with ataxia

PMID 36473599
- Data collected from 73 individuals studying the natural history of TANGO2 deficiency disorder. 94% of individuals (65/69) had ataxia as a feature. Ataxia was one of the symptoms found to occur between the ages of 1 to 3 years and of the first symptoms noted.

PMID 32527145
- Case report of a 6-year old girl diagnosed with TANGO2-related disease. By the age of 29 months, she had developed ataxia that worsened with viral illnesses and seizures and was recurrent in nature

Clinical Experience of a patient who had episodic ataxia as one of their presenting features. Testing in the hereditary ataxia panel did not find any pathogenic variants as the TANGO2 gene is not present on the panel. A diagnosis was later achieved over 4 years later when it became evident they had learning difficulties and the R29 panel was activated.
Sources: Literature
Intellectual disability v6.16 ITSN1 John Taylor gene: ITSN1 was added
gene: ITSN1 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: ITSN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ITSN1 were set to Bruel et al., 2021 (PMID: 34707297):
Phenotypes for gene: ITSN1 were set to autism spectrum disorders; intellectual disability; epilepsy.
Penetrance for gene: ITSN1 were set to unknown
Review for gene: ITSN1 was set to GREEN
gene: ITSN1 was marked as current diagnostic
Added comment: Bruel et al 2021 (PMID: 34707297):
Recent studies in large cohorts of subjects with neurodevelopmental disorders have identified de novo variants in ITSN1 gene thereby suggesting that this gene is involved in the development of such disorders.

A worldwide collaboration identified ten novel patients from eight families with heterozygous truncating or missense variants in ITSN1 gene. All patients underwent detailed phenotypic and genetic assessment and data was collected and shared by healthcare givers.

In addition, four previously published patients from large meta-analysis studies were included.
In total, 7/14 patients presented a de novo variant in ITSN1. Frameshift, nonsense and splice site variants would be consistent with haploinsufficiency. gnomADv4.1 indicates the ITSN1 gene is intolerant to LoF variants and Decipher indicates a high haploinsufficiency index score.

All patients showed neurodevelopmental disorders from autism spectrum disorders (90%), intellectual disability (86%), and epilepsy (30%). Minor and inconstant dysmorphic features were observed. Gastro-intestinal problems including constipation, diarrhoea, and gastroesophageal reflux was reported in some patients. Intellectual disability (IQ test) was reported to range from mild to moderate. In two families, the ITSN1 variant was inherited from a paucisymptomatic father, who were reported to present with ADHD, or learning difficulties and autistic features. Patients 8,9, and 10 (Bruel et al., 2021) inherited the familial nonsense variant from their father (learning difficulties and autistic features) and one unaffected sibling was not found to have the variant.
Sources: Literature
Fetal anomalies v4.3 TLL1 Arina Puzriakova Classified gene: TLL1 as Green List (high evidence)
Fetal anomalies v4.3 TLL1 Arina Puzriakova Added comment: Comment on list classification: TLL1 was re-reviewed by the GMS specialist team and it was decided that this gene should be demoted from Green to Amber, in line with the review by Stephanie Allen (Birmingham Women's Hospital).
Fetal anomalies v4.3 TLL1 Arina Puzriakova Gene: tll1 has been classified as Green List (High Evidence).
Fetal anomalies v4.2 TLL1 Arina Puzriakova Tag Q2_24_demote_amber tag was added to gene: TLL1.
Tag Q2_24_NHS_review tag was added to gene: TLL1.
Fetal anomalies v4.2 CELSR1 Arina Puzriakova Classified gene: CELSR1 as Green List (high evidence)
Fetal anomalies v4.2 CELSR1 Arina Puzriakova Added comment: Comment on list classification: CELSR1 was re-reviewed by the GMS specialist team and it was decided that this gene should be demoted from Green to Amber, in line with the review by Stephanie Allen (Birmingham Women's Hospital).
Fetal anomalies v4.2 CELSR1 Arina Puzriakova Gene: celsr1 has been classified as Green List (High Evidence).
Fetal anomalies v4.1 CELSR1 Arina Puzriakova Tag Q2_24_demote_amber tag was added to gene: CELSR1.
Tag Q2_24_NHS_review tag was added to gene: CELSR1.
Hypertrophic cardiomyopathy v4.13 TBX20 Sarah Leigh Entity copied from Dilated and arrhythmogenic cardiomyopathy v2.31
Hypertrophic cardiomyopathy v4.13 TBX20 Sarah Leigh gene: TBX20 was added
gene: TBX20 was added to Hypertrophic cardiomyopathy. Sources: Expert Review Amber,NHS GMS
Q2_24_promote_green tags were added to gene: TBX20.
Mode of inheritance for gene: TBX20 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TBX20 were set to 17668378; 19762328; 37657916; 33585493; 29089047; 35282022
Phenotypes for gene: TBX20 were set to Atrial septal defect 4, OMIM:611363; atrial septal defect 4, MONDO:0012654; Dilated cardiomyopathy, MONDO:0005021
Dilated and arrhythmogenic cardiomyopathy v2.31 TBX20 Sarah Leigh Tag Q2_24_promote_green tag was added to gene: TBX20.
Familial non syndromic congenital heart disease v1.86 TBX20 Sarah Leigh Classified gene: TBX20 as Green List (high evidence)
Familial non syndromic congenital heart disease v1.86 TBX20 Sarah Leigh Gene: tbx20 has been classified as Green List (High Evidence).
Dilated Cardiomyopathy and conduction defects v1.94 TBX20 Sarah Leigh Mode of inheritance for gene: TBX20 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Familial non syndromic congenital heart disease v1.85 TBX20 Sarah Leigh Mode of inheritance for gene: TBX20 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Dilated and arrhythmogenic cardiomyopathy v2.31 TBX20 Sarah Leigh commented on gene: TBX20: Three TBX20 variants have been associated with Atrial septal defect 4, in OMIM and Gen2Phen (PMID:17668378; 19762328) and seven TBX20 variants have been associated with Left ventricular noncompaction (LVNC)(PMID:37657916; 29089047; 35282022).
Dilated Cardiomyopathy and conduction defects v1.93 TBX20 Sarah Leigh Mode of inheritance for gene: TBX20 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Familial non syndromic congenital heart disease v1.84 TBX20 Sarah Leigh reviewed gene: TBX20: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Dilated Cardiomyopathy and conduction defects v1.92 TBX20 Sarah Leigh Mode of inheritance for gene: TBX20 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Dilated Cardiomyopathy and conduction defects v1.91 TBX20 Sarah Leigh Classified gene: TBX20 as Green List (high evidence)
Dilated Cardiomyopathy and conduction defects v1.91 TBX20 Sarah Leigh Gene: tbx20 has been classified as Green List (High Evidence).
Dilated Cardiomyopathy and conduction defects v1.90 TBX20 Sarah Leigh reviewed gene: TBX20: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Dilated and arrhythmogenic cardiomyopathy v2.31 TBX20 Sarah Leigh reviewed gene: TBX20: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Dilated and arrhythmogenic cardiomyopathy v2.31 TBX20 Sarah Leigh Publications for gene: TBX20 were set to 17668378; 19762328; 37657916
Dilated Cardiomyopathy and conduction defects v1.90 TBX20 Sarah Leigh Publications for gene: TBX20 were set to
Familial non syndromic congenital heart disease v1.84 TBX20 Sarah Leigh Publications for gene: TBX20 were set to 17668378; 19762328; 37657916
Dilated Cardiomyopathy and conduction defects v1.89 TBX20 Sarah Leigh Phenotypes for gene: TBX20 were changed from to Atrial septal defect 4, OMIM:611363; atrial septal defect 4, MONDO:0012654; Dilated cardiomyopathy, MONDO:0005021
Familial non syndromic congenital heart disease v1.83 TBX20 Sarah Leigh Phenotypes for gene: TBX20 were changed from Atrial septal defect 4, OMIM:611363; atrial septal defect 4, MONDO:0012654 to Atrial septal defect 4, OMIM:611363; atrial septal defect 4, MONDO:0012654; Dilated cardiomyopathy, MONDO:0005021
Dilated and arrhythmogenic cardiomyopathy v2.30 TBX20 Sarah Leigh Phenotypes for gene: TBX20 were changed from Atrial septal defect 4, OMIM:611363; atrial septal defect 4, MONDO:0012654 to Atrial septal defect 4, OMIM:611363; atrial septal defect 4, MONDO:0012654; Dilated cardiomyopathy, MONDO:0005021
Inherited pancreatic cancer v2.7 STK11 Sarah Leigh Phenotypes for gene: STK11 were changed from Pancreatic cancer, somatic, OMIM:260350 to Pancreatic cancer, somatic, OMIM:260350; familial pancreatic carcinoma, MONDO:0015278
Inherited pancreatic cancer v2.6 STK11 Sarah Leigh Publications for gene: STK11 were set to 30558719
Inherited pancreatic cancer v2.5 STK11 Sarah Leigh reviewed gene: STK11: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Inherited pancreatic cancer v2.5 STK11 Sarah Leigh Tag Q2_24_promote_green tag was added to gene: STK11.
Tag Q2_24_NHS_review tag was added to gene: STK11.
Inherited pancreatic cancer v2.5 STK11 Sarah Leigh Classified gene: STK11 as Amber List (moderate evidence)
Inherited pancreatic cancer v2.5 STK11 Sarah Leigh Gene: stk11 has been classified as Amber List (Moderate Evidence).
Inherited pancreatic cancer v2.4 ATM Sarah Leigh reviewed gene: ATM: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Inherited pancreatic cancer v2.4 ATM Sarah Leigh Tag Q2_24_promote_green tag was added to gene: ATM.
Tag Q2_24_MOI tag was added to gene: ATM.
Tag Q2_24_NHS_review tag was added to gene: ATM.
Inherited pancreatic cancer v2.4 ATM Sarah Leigh Classified gene: ATM as Amber List (moderate evidence)
Inherited pancreatic cancer v2.4 ATM Sarah Leigh Gene: atm has been classified as Amber List (Moderate Evidence).
Laterality disorders and isomerism v3.15 ARL2BP Sarah Leigh Tag Q2_24_promote_green tag was added to gene: ARL2BP.
Tag Q2_24_MOI tag was added to gene: ARL2BP.
Tag Q2_24_NHS_review tag was added to gene: ARL2BP.
Laterality disorders and isomerism v3.15 ARL2BP Sarah Leigh Publications for gene: ARL2BP were set to 36507858; 38649918; 23849777; 31425546
Laterality disorders and isomerism v3.14 ARL2BP Sarah Leigh reviewed gene: ARL2BP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Laterality disorders and isomerism v3.14 ARL2BP Sarah Leigh Phenotypes for gene: ARL2BP were changed from Retinitis pigmentosa with or without situs inversus, OMIM:615434 to Retinitis pigmentosa with or without situs inversus, OMIM:615434; retinitis pigmentosa with or without situs inversus, MONDO:0014186
Laterality disorders and isomerism v3.13 ARL2BP Sarah Leigh Phenotypes for gene: ARL2BP were changed from Situs Inversus to Retinitis pigmentosa with or without situs inversus, OMIM:615434
Laterality disorders and isomerism v3.12 ARL2BP Sarah Leigh Publications for gene: ARL2BP were set to 36507858; 38649918; 38649918
Laterality disorders and isomerism v3.11 ARL2BP Sarah Leigh Classified gene: ARL2BP as Amber List (moderate evidence)
Laterality disorders and isomerism v3.11 ARL2BP Sarah Leigh Gene: arl2bp has been classified as Amber List (Moderate Evidence).
Dilated and arrhythmogenic cardiomyopathy v2.29 PRDM16 Sarah Leigh Tag Q2_24_promote_green tag was added to gene: PRDM16.
Tag Q2_24_NHS_review tag was added to gene: PRDM16.
Dilated and arrhythmogenic cardiomyopathy v2.29 PRDM16 Sarah Leigh reviewed gene: PRDM16: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Dilated Cardiomyopathy and conduction defects v1.88 PRDM16 Sarah Leigh reviewed gene: PRDM16: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Dilated Cardiomyopathy and conduction defects v1.88 PRDM16 Sarah Leigh Classified gene: PRDM16 as Green List (high evidence)
Dilated Cardiomyopathy and conduction defects v1.88 PRDM16 Sarah Leigh Gene: prdm16 has been classified as Green List (High Evidence).
Dilated Cardiomyopathy and conduction defects v1.87 PRDM16 Sarah Leigh Phenotypes for gene: PRDM16 were changed from Cardiomyopathy, dilated, 1LL to Cardiomyopathy, dilated, 1LL, OMIM:615373; Left ventricular noncompaction 8, OMIM:615373; left ventricular noncompaction 8, MONDO:0014152
Dilated and arrhythmogenic cardiomyopathy v2.29 PRDM16 Sarah Leigh Phenotypes for gene: PRDM16 were changed from to Cardiomyopathy, dilated, 1LL, OMIM:615373; Left ventricular noncompaction 8, OMIM:615373; left ventricular noncompaction 8, MONDO:0014152
Dilated and arrhythmogenic cardiomyopathy v2.28 PRDM16 Sarah Leigh Publications for gene: PRDM16 were set to
Dilated Cardiomyopathy and conduction defects v1.86 PRDM16 Sarah Leigh Publications for gene: PRDM16 were set to
Skeletal dysplasia v5.4 CBFB Sarah Leigh Entity copied from Cleidocranial Dysplasia v1.4
Skeletal dysplasia v5.4 CBFB Sarah Leigh gene: CBFB was added
gene: CBFB was added to Skeletal dysplasia. Sources: Literature,Expert Review Amber
Q2_24_promote_green, Q2_24_MOI, Q2_24_NHS_review tags were added to gene: CBFB.
Mode of inheritance for gene: CBFB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CBFB were set to 36241386
Phenotypes for gene: CBFB were set to Cleidocranial dysplasia 2, OMIM:620099; cleidocranial dysplasia 2, MONDO:0859307
Penetrance for gene: CBFB were set to Complete
Cleidocranial Dysplasia v1.4 CBFB Sarah Leigh Phenotypes for gene: CBFB were changed from cleidocranial dysplasia; dental anomalies such as supernumery teeth and eruption failure; developmental delay (variable); shortening of the distal phalanges to Cleidocranial dysplasia 2, OMIM:620099; cleidocranial dysplasia 2, MONDO:0859307
Cleidocranial Dysplasia v1.3 CBFB Sarah Leigh Publications for gene: CBFB were set to PMID: 36241386
Cleidocranial Dysplasia v1.2 CBFB Sarah Leigh Tag Q2_24_promote_green tag was added to gene: CBFB.
Tag Q2_24_MOI tag was added to gene: CBFB.
Tag Q2_24_NHS_review tag was added to gene: CBFB.
Cleidocranial Dysplasia v1.2 CBFB Sarah Leigh Classified gene: CBFB as Amber List (moderate evidence)
Cleidocranial Dysplasia v1.2 CBFB Sarah Leigh Gene: cbfb has been classified as Amber List (Moderate Evidence).
Cleidocranial Dysplasia v1.1 CBFB Sarah Leigh reviewed gene: CBFB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Familial non syndromic congenital heart disease v1.82 TBX20 Sarah Leigh Publications for gene: TBX20 were set to 17668378, 19762328
Dilated and arrhythmogenic cardiomyopathy v2.27 TBX20 Sarah Leigh Publications for gene: TBX20 were set to
Familial non syndromic congenital heart disease v1.81 TBX20 Sarah Leigh Phenotypes for gene: TBX20 were changed from Atrial septal defect 4 611363 to Atrial septal defect 4, OMIM:611363; atrial septal defect 4, MONDO:0012654
Dilated and arrhythmogenic cardiomyopathy v2.26 TBX20 Sarah Leigh Phenotypes for gene: TBX20 were changed from to Atrial septal defect 4, OMIM:611363; atrial septal defect 4, MONDO:0012654
Early onset or syndromic epilepsy v5.13 ANO4 Sarah Leigh commented on gene: ANO4: To date, no phenotype has been associated with ANO4 variants in OMIM, Gen2Phen or Mondo.
Intellectual disability v6.16 ANO4 Sarah Leigh commented on gene: ANO4: To date, no phenotype has been associated with ANO4 variants in OMIM, Gen2Phen or Mondo.
Early onset or syndromic epilepsy v5.13 ANO4 Sarah Leigh Phenotypes for gene: ANO4 were changed from to sporadic encephalopathic and familial epilepsy
Intellectual disability v6.16 ANO4 Sarah Leigh Phenotypes for gene: ANO4 were changed from to sporadic encephalopathic and familial epilepsy
Intellectual disability v6.15 ANO4 Sarah Leigh Classified gene: ANO4 as Amber List (moderate evidence)
Intellectual disability v6.15 ANO4 Sarah Leigh Gene: ano4 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v5.12 ANO4 Sarah Leigh Classified gene: ANO4 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v5.12 ANO4 Sarah Leigh Gene: ano4 has been classified as Amber List (Moderate Evidence).
Intellectual disability v6.14 ANO4 Sarah Leigh gene: ANO4 was added
gene: ANO4 was added to Intellectual disability. Sources: Literature
Q2_24_promote_green, Q2_24_MOI tags were added to gene: ANO4.
Mode of inheritance for gene: ANO4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ANO4 were set to 38744284
Mode of pathogenicity for gene: ANO4 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: ANO4 was set to GREEN
Added comment: PMID: 38744284 reports five de novo ANO4 missense variants in patients (I1–I5) with a phenotype that includes intellectual disability, developmental and epileptic or epileptic encephalopathy (DEE/EE) and hypotonia. A further two ANO4 missenses variants were observed, one had been inherited from unaffected mother (patient F7) and with a penetrance of 73% in members of a large pedigree with a milder phenotype (PMID: 38744284: Supplementary figure S2). Febrile seizures plus (GEFS+) or temporal lobe epilepsy were associated with these inherited variants. A dominant negative mechanism was proposed by Yang et al (PMID: 38744284) as a result of functional studies of one of the variants causing DEE/EE and one causing GEFS+.
Sources: Literature
Early onset or syndromic epilepsy v5.11 ANO4 Sarah Leigh gene: ANO4 was added
gene: ANO4 was added to Early onset or syndromic epilepsy. Sources: Literature
Q2_24_promote_green, Q2_24_MOI tags were added to gene: ANO4.
Mode of inheritance for gene: ANO4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ANO4 were set to 38744284
Mode of pathogenicity for gene: ANO4 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: ANO4 was set to GREEN
Added comment: PMID: 38744284 reports five de novo ANO4 missense variants in patients (I1–I5) with a phenotype that includes intellectual disability, developmental and epileptic or epileptic encephalopathy (DEE/EE) and hypotonia. A further two ANO4 missenses variants were observed, one had been inherited from unaffected mother (patient F7) and with a penetrance of 73% in members of a large pedigree with a milder phenotype (PMID: 38744284: Supplementary figure S2). Febrile seizures plus (GEFS+) or temporal lobe epilepsy were associated with these inherited variants. A dominant negative mechanism was proposed by Yang et al (PMID: 38744284) as a result of functional studies of one of the variants causing DEE/EE and one causing GEFS+.
Sources: Literature
Monogenic short stature v0.176 PAPPA2 Arina Puzriakova Publications for gene: PAPPA2 were set to 26902202; 33875846
Monogenic short stature v0.175 PAPPA2 Arina Puzriakova commented on gene: PAPPA2: Inclusion of the PAPPA2 gene on this panel was previously reviewed and disagreed by the GMS expert group. However, this should now be re-evaluated in light of the new review Melissa Connolly (WMRGL GLH) stating that inclusion would benefit GLH interpretation.
Monogenic short stature v0.175 PAPPA2 Arina Puzriakova Tag Q1_24_promote_green tag was added to gene: PAPPA2.
Tag Q1_24_NHS_review tag was added to gene: PAPPA2.
Tag Q1_24_expert_review tag was added to gene: PAPPA2.
Autoinflammatory disorders v2.3 OGFRL1 Arina Puzriakova Classified gene: OGFRL1 as Amber List (moderate evidence)
Autoinflammatory disorders v2.3 OGFRL1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Hannah Knight. Rating Amber, awaiting further cases. To date, a single publication (PMID: 38699440) has reported two unrelated cherubism families with homozygous variants in this gene.
Autoinflammatory disorders v2.3 OGFRL1 Arina Puzriakova Gene: ogfrl1 has been classified as Amber List (Moderate Evidence).
Autoinflammatory disorders v2.2 OGFRL1 Arina Puzriakova Publications for gene: OGFRL1 were set to PMID: 38699440
Fetal anomalies v4.1 MDFIC Dmitrijs Rots gene: MDFIC was added
gene: MDFIC was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: MDFIC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MDFIC were set to PMID: 35235341
Phenotypes for gene: MDFIC were set to conducting lymphatic anomaly with lymphedema
Review for gene: MDFIC was set to GREEN
Added comment: Six independet families with specific phenotype and AR inheritance + mouse model. Enough for green rating.
Sources: Literature
Fetal anomalies v4.1 CELSR1 Stephanie Allen changed review comment from: This gene and phenotype were re-reviewed by the fetal anomaly panel review group in May 2024. Suggest downgrade to amber:
Clingen presentation - 3 phenotypes linked NTD as a susceptibility locus only, epilepsy no obvious prenatal link. Lymphatic malformations good evidence for truncating variants only. Variable expressivity/penetrance in males. Females earliest onset reported form birth but no evidence of hydrops. Usual onset adolescents. Not enough evidence, suggest Amber to watch for link to hydrops.; to: This gene and phenotype were re-reviewed by the fetal anomaly panel review group in May 2024. Suggest downgrade to amber:
Clingen presentation - 3 phenotypes linked NTD as a susceptibility locus only, epilepsy no obvious prenatal link. Lymphatic malformations good evidence for truncating variants only. Variable expressivity/penetrance in males. Females earliest onset reported form birth but no evidence of hydrops. Usual onset adolescents. Not enough evidence, suggest Amber to watch for link to hydrops.
Fetal anomalies v4.1 TLL1 Stephanie Allen reviewed gene: TLL1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Fetal anomalies v4.1 CELSR1 Stephanie Allen reviewed gene: CELSR1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Diagnostic testing for MCADD - Medium-chain acyl-CoA dehydrogenase deficiency - full ACADM sequencing v0.3 Achchuthan Shanmugasundram Panel name changed from Diagnostic testing for MCADD - Medium-chain acyl-CoA dehydrogenase deficiency – full ACADM sequencing to Diagnostic testing for MCADD - Medium-chain acyl-CoA dehydrogenase deficiency - full ACADM sequencing
Likely inborn error of metabolism v5.3 RNASEH2C Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: RNASEH2C.
Tag Q1_24_NHS_review tag was added to gene: RNASEH2C.
Likely inborn error of metabolism v5.3 RNASEH2C Achchuthan Shanmugasundram Tag Q1_22_NHS_review was removed from gene: RNASEH2C.
Tag Q1_24_promote_green was removed from gene: RNASEH2C.
NARP syndrome or maternally inherited Leigh syndrome v1.3 MT-ND6 Achchuthan Shanmugasundram Tag curated_removed tag was added to gene: MT-ND6.
NARP syndrome or maternally inherited Leigh syndrome v1.3 MT-ND6 Achchuthan Shanmugasundram edited their review of gene: MT-ND6: Changed rating: RED
NARP syndrome or maternally inherited Leigh syndrome v1.3 MT-ND6 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreyfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to grey following NHS Genomic Medicine Service approval.
NARP syndrome or maternally inherited Leigh syndrome v1.3 MT-ND6 Achchuthan Shanmugasundram commented on gene: MT-ND6: The rating of this gene has been updated togreyfollowing NHS Genomic Medicine Service approval.
NARP syndrome or maternally inherited Leigh syndrome v1.2 MT-ND6 Achchuthan Shanmugasundram Source Expert Review Removed was added to MT-ND6.
Rating Changed from Green List (high evidence) to No List (delete)
Inherited phaeochromocytoma and paraganglioma excluding NF1 v2.8 SLC25A11 Achchuthan Shanmugasundram Tag curated_removed tag was added to gene: SLC25A11.
Inherited phaeochromocytoma and paraganglioma excluding NF1 v2.8 MDH2 Achchuthan Shanmugasundram Tag curated_removed tag was added to gene: MDH2.
Inherited phaeochromocytoma and paraganglioma excluding NF1 v2.8 SLC25A11 Achchuthan Shanmugasundram Tag Q4_23_demote_red was removed from gene: SLC25A11.
Tag Q4_23_NHS_review was removed from gene: SLC25A11.
Tag Q4_23_expert_review was removed from gene: SLC25A11.
Inherited phaeochromocytoma and paraganglioma excluding NF1 v2.8 SLC25A11 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreyfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to grey following NHS Genomic Medicine Service approval.
Inherited phaeochromocytoma and paraganglioma excluding NF1 v2.8 MDH2 Achchuthan Shanmugasundram Tag Q4_23_demote_red was removed from gene: MDH2.
Tag Q4_23_NHS_review was removed from gene: MDH2.
Tag Q4_23_expert_review was removed from gene: MDH2.
Inherited phaeochromocytoma and paraganglioma excluding NF1 v2.8 MDH2 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreyfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to grey following NHS Genomic Medicine Service approval.
Inherited phaeochromocytoma and paraganglioma excluding NF1 v2.8 DLST Achchuthan Shanmugasundram Tag Q4_23_demote_red was removed from gene: DLST.
Tag Q4_23_NHS_review was removed from gene: DLST.
Tag Q4_23_expert_review was removed from gene: DLST.
Tag curated_removed tag was added to gene: DLST.
Inherited phaeochromocytoma and paraganglioma excluding NF1 v2.8 DLST Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreyfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to grey following NHS Genomic Medicine Service approval.
Inherited phaeochromocytoma and paraganglioma excluding NF1 v2.8 DLST Achchuthan Shanmugasundram commented on gene: DLST
Inherited phaeochromocytoma and paraganglioma excluding NF1 v2.8 SLC25A11 Achchuthan Shanmugasundram commented on gene: SLC25A11
Inherited phaeochromocytoma and paraganglioma excluding NF1 v2.8 MDH2 Achchuthan Shanmugasundram commented on gene: MDH2
Inherited phaeochromocytoma and paraganglioma excluding NF1 v2.7 DLST Achchuthan Shanmugasundram Source Expert Review Removed was added to DLST.
Rating Changed from Green List (high evidence) to No List (delete)
Inherited phaeochromocytoma and paraganglioma excluding NF1 v2.7 SLC25A11 Achchuthan Shanmugasundram Source Expert Review Removed was added to SLC25A11.
Rating Changed from Green List (high evidence) to No List (delete)
Inherited phaeochromocytoma and paraganglioma excluding NF1 v2.7 MDH2 Achchuthan Shanmugasundram Source Expert Review Removed was added to MDH2.
Rating Changed from Green List (high evidence) to No List (delete)
Diagnostic testing for MCADD - Medium-chain acyl-CoA dehydrogenase deficiency - full ACADM sequencing v0.2 ACADM Achchuthan Shanmugasundram reviewed gene: ACADM: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Diagnostic testing for MCADD - Medium-chain acyl-CoA dehydrogenase deficiency - full ACADM sequencing v0.2 ACADM Achchuthan Shanmugasundram Classified gene: ACADM as Green List (high evidence)
Diagnostic testing for MCADD - Medium-chain acyl-CoA dehydrogenase deficiency - full ACADM sequencing v0.2 ACADM Achchuthan Shanmugasundram Gene: acadm has been classified as Green List (High Evidence).
Diagnostic testing for Isovaleric acidaemia v0.4 IVD Achchuthan Shanmugasundram reviewed gene: IVD: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Diagnostic testing for Isovaleric acidaemia v0.3 IVD Achchuthan Shanmugasundram Source Expert Review Green was added to IVD.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Diagnostic testing for Glutaric acidaemia I v0.3 GCDH Achchuthan Shanmugasundram reviewed gene: GCDH: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Diagnostic testing for Glutaric acidaemia I v0.2 GCDH Achchuthan Shanmugasundram Source Expert Review Green was added to GCDH.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Monogenic short stature v0.175 PAPPA2 Achchuthan Shanmugasundram changed review comment from: The following is the review left by Melissa Connolly (WMRGL GLH) for this gene in R147 Growth failure in early childhood panel (https://panelapp.genomicsengland.co.uk/panels/473/gene/PAPPA2/):

The addition of this gene to the panel would be useful from a GLH perspective for interpretation purposes. ACGS guidelines state that when trying to incorporate phenotypic data into classification of variants that all other known causes of the phenotype should be excluded. In practice we often receive biochemical data for patients who have abnormal endocrine results in the GH-IGF axis and using this information for assessment of variants becomes easier if all the genes known to cause defects in the GH-IGF1 axis have been included in the analysis.

Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal

Phenotypes: Short stature; dysmorphism; mild microcephaly

Publications: 31555216; Durkie et al, 2024 https://www.acgs.uk.com/media/12533/uk-practice-guidelines-for-variant-classification-v12-2024.pdf; to: The following is the review left by Melissa Connolly (WMRGL GLH) for this gene in R147 Growth failure in early childhood panel (https://panelapp.genomicsengland.co.uk/panels/473/gene/PAPPA2/):

The addition of this gene to the panel would be useful from a GLH perspective for interpretation purposes. ACGS guidelines state that when trying to incorporate phenotypic data into classification of variants that all other known causes of the phenotype should be excluded. In practice we often receive biochemical data for patients who have abnormal endocrine results in the GH-IGF axis and using this information for assessment of variants becomes easier if all the genes known to cause defects in the GH-IGF1 axis have been included in the analysis.

Rating: Green List (high evidence)
Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Phenotypes: Short stature; dysmorphism; mild microcephaly
Publications: 31555216; Durkie et al, 2024 https://www.acgs.uk.com/media/12533/uk-practice-guidelines-for-variant-classification-v12-2024.pdf
Monogenic short stature v0.175 PAPPA2 Achchuthan Shanmugasundram commented on gene: PAPPA2: The following is the review left by Melissa Connolly (WMRGL GLH) for this gene in R147 Growth failure in early childhood panel (https://panelapp.genomicsengland.co.uk/panels/473/gene/PAPPA2/):

The addition of this gene to the panel would be useful from a GLH perspective for interpretation purposes. ACGS guidelines state that when trying to incorporate phenotypic data into classification of variants that all other known causes of the phenotype should be excluded. In practice we often receive biochemical data for patients who have abnormal endocrine results in the GH-IGF axis and using this information for assessment of variants becomes easier if all the genes known to cause defects in the GH-IGF1 axis have been included in the analysis.

Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal

Phenotypes: Short stature; dysmorphism; mild microcephaly

Publications: 31555216; Durkie et al, 2024 https://www.acgs.uk.com/media/12533/uk-practice-guidelines-for-variant-classification-v12-2024.pdf
Arthrogryposis v6.7 SLC35A3 Achchuthan Shanmugasundram Classified gene: SLC35A3 as Amber List (moderate evidence)
Arthrogryposis v6.7 SLC35A3 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Hannah Knight, there are 12 affected individuals from four different families reported with biallelic SLC35A3 variants and arthrogryposis. Hence, this gene can be promoted to green rating in the next GMS review.
Arthrogryposis v6.7 SLC35A3 Achchuthan Shanmugasundram Gene: slc35a3 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v6.6 SLC35A3 Achchuthan Shanmugasundram Phenotypes for gene: SLC35A3 were changed from Arthrogryposis, impaired intellectual development, and seizures, OMIM:615553 to Arthrogryposis, impaired intellectual development, and seizures, OMIM:615553
Arthrogryposis v6.5 SLC35A3 Achchuthan Shanmugasundram Phenotypes for gene: SLC35A3 were changed from Arthrogryposis, mental retardation, and seizures 615553 to Arthrogryposis, impaired intellectual development, and seizures, OMIM:615553
Arthrogryposis v6.4 SLC35A3 Achchuthan Shanmugasundram Publications for gene: SLC35A3 were set to 24031089
Arthrogryposis v6.3 SLC35A3 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: SLC35A3.
Tag Q2_24_NHS_review tag was added to gene: SLC35A3.
Arthrogryposis v6.3 SLC35A3 Achchuthan Shanmugasundram reviewed gene: SLC35A3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Arthrogryposis, impaired intellectual development, and seizures, OMIM:615553; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v5.6 PQLC2 Achchuthan Shanmugasundram Classified gene: PQLC2 as Amber List (moderate evidence)
Retinal disorders v5.6 PQLC2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are six unrelated families/ cases reported with biallelic SLC66A1 variants and retinal disorders. Hence, this gene should be promoted to green rating in the next GMS review.
Retinal disorders v5.6 PQLC2 Achchuthan Shanmugasundram Gene: pqlc2 has been classified as Amber List (Moderate Evidence).
Retinal disorders v5.5 PQLC2 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: PQLC2.
Retinal disorders v5.5 PQLC2 Achchuthan Shanmugasundram commented on gene: PQLC2: HGNC Gene Symbol: SLC66A1. Hence, 'new-gene-name' tag added.
Retinal disorders v5.5 PQLC2 Achchuthan Shanmugasundram Tag new-gene-name tag was added to gene: PQLC2.
Retinal disorders v5.5 PQLC2 Achchuthan Shanmugasundram gene: PQLC2 was added
gene: PQLC2 was added to Retinal disorders. Sources: Literature
Mode of inheritance for gene: PQLC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PQLC2 were set to 35486108
Phenotypes for gene: PQLC2 were set to Retinitis pigmentosa, MONDO:0019200
Review for gene: PQLC2 was set to GREEN
Added comment: PMID:35486108 reported whole-exome sequencing with targeted analysis of SLC genes in 913 cases from 785 families with inherited retinal dystrophy. This identified 2 different homozygous variants in SLC66A1 in three individuals from two families with adult-onset retinal dystrophy.

Olinger et al. (2024) (https://www.sciencedirect.com/science/article/pii/S2949774424009804) reported CNV analysis of trio and non-trio WGS data from Genomics England 100K genomes project. This identified homozygous 21kb deletion spanning nearly entire SLC66A1 gene in 2 siblings with adult-onset rod-cone dystrophy, while parents are heterozygous carriers. Review of cohort data then identified homozygous loss-of-function variants (1 nonsense, 2 frameshift) in another 3 unrelated individuals with rod-cone dystrophy.

This gene has not yet been associated with any relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Paediatric or syndromic cardiomyopathy v4.6 MT-TI Achchuthan Shanmugasundram Classified gene: MT-TI as Amber List (moderate evidence)
Paediatric or syndromic cardiomyopathy v4.6 MT-TI Achchuthan Shanmugasundram Added comment: Comment on list classification: There are at least three unrelated cases reported with infantile-onset/ paediatric-onset cardiomyopathy and hence this gene can be promoted to green rating in the next GMS update.
Paediatric or syndromic cardiomyopathy v4.6 MT-TI Achchuthan Shanmugasundram Gene: mt-ti has been classified as Amber List (Moderate Evidence).
Paediatric or syndromic cardiomyopathy v4.5 MT-TI Achchuthan Shanmugasundram Phenotypes for gene: MT-TI were changed from to familial hypertrophic cardiomyopathy, MONDO:0024573; familial dilated cardiomyopathy, MONDO:0016333
Paediatric or syndromic cardiomyopathy v4.4 MT-TI Achchuthan Shanmugasundram Publications for gene: MT-TI were set to
Paediatric or syndromic cardiomyopathy v4.3 MT-TI Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: MT-TI.
Paediatric or syndromic cardiomyopathy v4.3 MT-TI Achchuthan Shanmugasundram reviewed gene: MT-TI: Rating: GREEN; Mode of pathogenicity: None; Publications: 12767666, 21945886, 23332932, 29481798, 30025578; Phenotypes: familial hypertrophic cardiomyopathy, MONDO:0024573, familial dilated cardiomyopathy, MONDO:0016333; Mode of inheritance: MITOCHONDRIAL
Malformations of cortical development v5.5 COL3A1 Eleanor Williams Classified gene: COL3A1 as Amber List (moderate evidence)
Malformations of cortical development v5.5 COL3A1 Eleanor Williams Added comment: Comment on list classification: Promoting this gene to amber, with a recommendation for green rating following GMS review.
Malformations of cortical development v5.5 COL3A1 Eleanor Williams Gene: col3a1 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v5.4 COL3A1 Eleanor Williams Tag Q2_24_promote_green tag was added to gene: COL3A1.
Malformations of cortical development v5.4 COL3A1 Eleanor Williams changed review comment from: Associated with Polymicrogyria with or without vascular-type EDS in OMIM (OMIM:618343) with a autosomal recessive mode of inheritance.

Several cases reported:

PMID: 19455184 Plancke et al 2009 - report an 11 year old female with consangiuneous parents, who had vascular EDS. The phenotype also included diffuse cortical dysplasia. A homozygous nucleotide duplication (c.479dupT) in COL3A1 resulting in a premature termination codon (p.Lys161GlnfsX45) was identified. Both parents were heterozygous for this variant.

PMID: 25205403 Jørgensen et al 2015 - report 2 siblings who are compound heterozygous for COL3A1 sequence variants. One sibling died suddenly due to extensive aortic dissection at age 15. The younger sibling was cerebral cortical dysplasia with thickened frontoparietal cortices bilaterally, small gyri and findings consistent with pachy micropolygyria

PMID:28742248 - Horn et al 2017 identified biallelic COL3A1 variants in two unrelated families. A 3-year-old female with developmental delay was compound het for a nonsense variant c.1282C>T, p.(Arg428*) and a frameshift variant c.2057delC, p.(Pro686Leufs*105). The patient phenotype at birth was bilateral clubfoot, joint laxity, and dysmorphic facial features an at age 2 years cerebral MRI showed a profound cerebral abnormalities including bilateral frontoparietal polymicrogyria of the cobblestone variant. In the second family, the two affected siblings were homozygous for the missense variant c.145C<G, p.(Pro49Ala) of COL3A1 and showed cobblestone-like cortical malformation, cerebellar cysts, and white matter abnormalities, developmental delay, and seizures.

PMID: 28258187 - Vandervore et al 2017 - exome analysis of a family consisting of two affected and two non-affected siblings identified a novel homozygous variant c.145C>G (p.Pro49Ala) in exon 2 of COL3A1 in the affected siblings. Both patients had cobblestone-like malformation of the cortex and the white matter was severely abnormal.
; to: Associated with Polymicrogyria with or without vascular-type EDS in OMIM (OMIM:618343) with a autosomal recessive mode of inheritance.

Several cases reported:

PMID: 19455184 Plancke et al 2009 - report an 11 year old female with consangiuneous parents, who had vascular EDS. The phenotype also included diffuse cortical dysplasia. A homozygous nucleotide duplication (c.479dupT) in COL3A1 resulting in a premature termination codon (p.Lys161GlnfsX45) was identified. Both parents were heterozygous for this variant.

PMID: 25205403 Jørgensen et al 2015 - report 2 siblings who are compound heterozygous for COL3A1 sequence variants. One sibling died suddenly due to extensive aortic dissection at age 15. The younger sibling was cerebral cortical dysplasia with thickened frontoparietal cortices bilaterally, small gyri and findings consistent with pachy micropolygyria

PMID:28742248 - Horn et al 2017 identified biallelic COL3A1 variants in two unrelated families. A 3-year-old female with developmental delay was compound het for a nonsense variant c.1282C>T, p.(Arg428*) and a frameshift variant c.2057delC, p.(Pro686Leufs*105). The patient phenotype at birth was bilateral clubfoot, joint laxity, and dysmorphic facial features an at age 2 years cerebral MRI showed a profound cerebral abnormalities including bilateral frontoparietal polymicrogyria of the cobblestone variant. In the second family (born of unrelated parents from Chechnya and Ingushetia), the two affected siblings were homozygous for the missense variant c.145C<G, p.(Pro49Ala) of COL3A1 and showed cobblestone-like cortical malformation, cerebellar cysts, and white matter abnormalities, developmental delay, and seizures.

PMID: 28258187 - Vandervore et al 2017 - exome analysis of a family with unrelated parents from the same mountain village in Chechnya, consisting of two affected and two non-affected siblings identified a novel homozygous variant c.145C>G (p.Pro49Ala) in exon 2 of COL3A1 in the affected siblings. Both patients had cobblestone-like malformation of the cortex and the white matter was severely abnormal.
Malformations of cortical development v5.4 COL3A1 Eleanor Williams changed review comment from: Associated with Polymicrogyria with or without vascular-type EDS in OMIM (OMIM:618343) with a autosomal recessive mode of inheritance.

Several cases reported:

PMID: 19455184 Plancke et al 2009 - report an 11 year old female with consangiuneous parents, who had vascular EDS. The phenotype also included diffuse cortical dysplasia. A homozygous nucleotide duplication (c.479dupT) in COL3A1 resulting in a premature termination codon (p.Lys161GlnfsX45) was identified. Both parents were heterozygous for this variant.

PMID: 25205403 Jørgensen et al 2015 - report 2 siblings who are compound heterozygous for COL3A1 sequence variants. One sibling died suddenly due to extensive aortic dissection at age 15. The younger sibling was cerebral cortical dysplasia with thickened frontoparietal cortices bilaterally, small gyri and findings consistent with pachy micropolygyria
Sources: Literature; to: Associated with Polymicrogyria with or without vascular-type EDS in OMIM (OMIM:618343) with a autosomal recessive mode of inheritance.

Several cases reported:

PMID: 19455184 Plancke et al 2009 - report an 11 year old female with consangiuneous parents, who had vascular EDS. The phenotype also included diffuse cortical dysplasia. A homozygous nucleotide duplication (c.479dupT) in COL3A1 resulting in a premature termination codon (p.Lys161GlnfsX45) was identified. Both parents were heterozygous for this variant.

PMID: 25205403 Jørgensen et al 2015 - report 2 siblings who are compound heterozygous for COL3A1 sequence variants. One sibling died suddenly due to extensive aortic dissection at age 15. The younger sibling was cerebral cortical dysplasia with thickened frontoparietal cortices bilaterally, small gyri and findings consistent with pachy micropolygyria

PMID:28742248 - Horn et al 2017 identified biallelic COL3A1 variants in two unrelated families. A 3-year-old female with developmental delay was compound het for a nonsense variant c.1282C>T, p.(Arg428*) and a frameshift variant c.2057delC, p.(Pro686Leufs*105). The patient phenotype at birth was bilateral clubfoot, joint laxity, and dysmorphic facial features an at age 2 years cerebral MRI showed a profound cerebral abnormalities including bilateral frontoparietal polymicrogyria of the cobblestone variant. In the second family, the two affected siblings were homozygous for the missense variant c.145C<G, p.(Pro49Ala) of COL3A1 and showed cobblestone-like cortical malformation, cerebellar cysts, and white matter abnormalities, developmental delay, and seizures.

PMID: 28258187 - Vandervore et al 2017 - exome analysis of a family consisting of two affected and two non-affected siblings identified a novel homozygous variant c.145C>G (p.Pro49Ala) in exon 2 of COL3A1 in the affected siblings. Both patients had cobblestone-like malformation of the cortex and the white matter was severely abnormal.
Monogenic hearing loss v4.41 MYO1A Barbara Vona reviewed gene: MYO1A: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 24616153; Phenotypes: ; Mode of inheritance: Other
Monogenic hearing loss v4.41 PKHD1L1 Barbara Vona gene: PKHD1L1 was added
gene: PKHD1L1 was added to Monogenic hearing loss. Sources: Literature
Mode of inheritance for gene: PKHD1L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PKHD1L1 were set to PMID: 38459354
Phenotypes for gene: PKHD1L1 were set to Hearing loss
Penetrance for gene: PKHD1L1 were set to Complete
Review for gene: PKHD1L1 was set to GREEN
gene: PKHD1L1 was marked as current diagnostic
Added comment: Through exome sequencing of four probands with autosomal recessive non-syndromic sensorineural hearing loss, biallelic variants were identified in PKHD1L1 (Redfield et al., 2024; PMID: 38459354). Hearing loss was of highly variable severities and ranged from mild to profound. It had a congenital (or suspected congenital) onset and was progressive. This work benefitted from two previously published models: a mouse model, showing progressive hearing loss in homozygous conditional knockout animals (Wu et al., 2019; PMID: 31444330) and a zebrafish study with zebrafish homozygous for knockout of both pkhd1l1-alpha and -beta having deficits in auditory startle response (Makrogkikas et al., 2023; PMID: 36960824). PKHD1L1 has been curated in OMIM as causing Autosomal Recessive Deafness 124 (DFNB124). Note that PKHD1L1 is a rather large gene, so variants should be carefully assessed for pathogenicity.
Sources: Literature
Laterality disorders and isomerism v3.10 ARL2BP Nour Elkhateeb changed review comment from: Biallelic ARL2BP variants are reported to be associated with Retinitis pigmentosa with or without situs inversus. Situs inversus is reported in several reports including PMID 36507858, 38649918, 38649918. ARL2BP is a ciliary gene associated with multiple ciliopathy phenotypes. ARL2BP murine knockout model showed similar phenotypes to humans, including retinal degeneration, immotile sperm cells and impaired spermatogenesis, as well as situs inversus and increased brain ventricular volume (PMID: 31425546).
Sources: Literature; to: Biallelic ARL2BP variants are reported to be associated with Retinitis pigmentosa with or without situs inversus. Situs inversus is reported in several reports including PMID 36507858, 38649918, 23849777. ARL2BP is a ciliary gene associated with multiple ciliopathy phenotypes. ARL2BP murine knockout model showed similar phenotypes to humans, including retinal degeneration, immotile sperm cells and impaired spermatogenesis, as well as situs inversus and increased brain ventricular volume (PMID: 31425546).
Sources: Literature
Laterality disorders and isomerism v3.10 ARL2BP Nour Elkhateeb gene: ARL2BP was added
gene: ARL2BP was added to Laterality disorders and isomerism. Sources: Literature
Mode of inheritance for gene: ARL2BP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARL2BP were set to 36507858; 38649918; 38649918
Phenotypes for gene: ARL2BP were set to Situs Inversus
Review for gene: ARL2BP was set to GREEN
Added comment: Biallelic ARL2BP variants are reported to be associated with Retinitis pigmentosa with or without situs inversus. Situs inversus is reported in several reports including PMID 36507858, 38649918, 38649918. ARL2BP is a ciliary gene associated with multiple ciliopathy phenotypes. ARL2BP murine knockout model showed similar phenotypes to humans, including retinal degeneration, immotile sperm cells and impaired spermatogenesis, as well as situs inversus and increased brain ventricular volume (PMID: 31425546).
Sources: Literature
Diagnostic testing for MCADD - Medium-chain acyl-CoA dehydrogenase deficiency - full ACADM sequencing v0.1 ACADM Achchuthan Shanmugasundram Deleted their review
Diagnostic testing for MCADD - Medium-chain acyl-CoA dehydrogenase deficiency - full ACADM sequencing v0.1 ACADM Achchuthan Shanmugasundram Deleted their comment
Diagnostic testing for MCADD - Medium-chain acyl-CoA dehydrogenase deficiency - full ACADM sequencing v0.1 ACADM Achchuthan Shanmugasundram gene: ACADM was added
gene: ACADM was added to Diagnostic testing for MCADD - Medium-chain acyl-CoA dehydrogenase deficiency – full ACADM sequencing. Sources: NHS GMS
Mode of inheritance for gene: ACADM was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ACADM were set to Acyl-CoA dehydrogenase, medium chain, deficiency of, OMIM:201450
Review for gene: ACADM was set to RED
Added comment: Sources: NHS GMS
Diagnostic testing for MCADD - Medium-chain acyl-CoA dehydrogenase deficiency - full ACADM sequencing v0.0 Achchuthan Shanmugasundram Added Panel Diagnostic testing for MCADD - Medium-chain acyl-CoA dehydrogenase deficiency – full ACADM sequencing
Set list of related panels to R451
Set panel types to: GMS Rare Disease
Diagnostic testing for Glutaric acidaemia I v0.1 GCDH Achchuthan Shanmugasundram gene: GCDH was added
gene: GCDH was added to Diagnostic testing for Glutaric acidaemia I. Sources: NHS GMS
Mode of inheritance for gene: GCDH was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GCDH were set to Glutaricaciduria, type I, OMIM:231670
Diagnostic testing for Glutaric acidaemia I v0.0 Achchuthan Shanmugasundram Added Panel Diagnostic testing for Glutaric acidaemia I
Set list of related panels to R449
Set panel types to: GMS Rare Disease
Diagnostic testing for Isovaleric acidaemia v0.2 Achchuthan Shanmugasundram Panel name changed from Isovaleric acidaemia to Diagnostic testing for Isovaleric acidaemia
Diagnostic testing for Isovaleric acidaemia v0.1 IVD Achchuthan Shanmugasundram gene: IVD was added
gene: IVD was added to Isovaleric acidaemia. Sources: NHS GMS
Mode of inheritance for gene: IVD was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IVD were set to Isovaleric acidemia, OMIM:243500
Diagnostic testing for Isovaleric acidaemia v0.0 Achchuthan Shanmugasundram Added Panel Isovaleric acidaemia
Set list of related panels to R450
Set panel types to: GMS Rare Disease
Intellectual disability v6.13 RNU4-2 Eleanor Williams commented on gene: RNU4-2
Hypertrophic cardiomyopathy v4.12 MT-TI Achchuthan Shanmugasundram Classified gene: MT-TI as Amber List (moderate evidence)
Hypertrophic cardiomyopathy v4.12 MT-TI Achchuthan Shanmugasundram Added comment: Comment on list classification: There are at least four unrelated cases with hypertrophic cardiomyopathy and hence this gene can be promoted to green rating in the next GMS review.
Hypertrophic cardiomyopathy v4.12 MT-TI Achchuthan Shanmugasundram Gene: mt-ti has been classified as Amber List (Moderate Evidence).
Hypertrophic cardiomyopathy v4.11 MT-TI Achchuthan Shanmugasundram Phenotypes for gene: MT-TI were changed from to familial hypertrophic cardiomyopathy, MONDO:0024573; familial dilated cardiomyopathy, MONDO:0016333
Hypertrophic cardiomyopathy v4.10 MT-TI Achchuthan Shanmugasundram Publications for gene: MT-TI were set to 12767666; 30025578
Hypertrophic cardiomyopathy v4.9 MT-TI Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: MT-TI.
Hypertrophic cardiomyopathy v4.9 MT-TI Achchuthan Shanmugasundram reviewed gene: MT-TI: Rating: GREEN; Mode of pathogenicity: None; Publications: 12767666, 21945886, 23332932, 29481798, 30025578; Phenotypes: familial hypertrophic cardiomyopathy, MONDO:0024573, familial dilated cardiomyopathy, MONDO:0016333; Mode of inheritance: MITOCHONDRIAL
Inherited pancreatic cancer v2.3 ATM Terri McVeigh gene: ATM was added
gene: ATM was added to Inherited pancreatic cancer. Sources: Other
Mode of inheritance for gene: ATM was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATM were set to 34529012; 33509806
Phenotypes for gene: ATM were set to Breast, prostate, pancreatic cancer predisposition; recessive trait for ataxia telangiectasia
Penetrance for gene: ATM were set to Incomplete
Mode of pathogenicity for gene: ATM was set to Other
Review for gene: ATM was set to GREEN
Added comment: Discussed at UKCGG/Cancer Leads meeting 29th February 2024 - consensus that ATM should be added to this panel for diagnostic testing in individuals with pancreatic cancer fulfilling eligibility criteria. Reporting of variants should be restricted to truncating variants, high-risk missense c.7271T/G and exceptional variants as determined by Can-VIG UK, as per other panels where ATM is tested for cancer predisposition (R208/430)
Sources: Other
Inherited pancreatic cancer v2.3 STK11 Terri McVeigh reviewed gene: STK11: Rating: GREEN; Mode of pathogenicity: None; Publications: 33513864, 11113065, 16707622, 23240097, 23415580; Phenotypes: Peutz-Jeghers syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital muscular dystrophy v4.24 FHL1 Sarah Leigh edited their review of gene: FHL1: Changed rating: GREEN
Congenital muscular dystrophy v4.24 FHL1 Sarah Leigh changed review comment from: In response to Zornitza Starks' review, Helen Brittain (Genomics England Clinical Fellow) was asked the following question: are the phenotypes of Reducing body myopathy, X-linked 1a, severe, infantile or early childhood onset (OMIM:300717) and/or Reducing body myopathy, X-linked 1b, with late childhood or adult onset (OMIM:300718), which are associated with FHL1 variants, appropriate for this panel - Congenital muscular dystrophy (R79)?
Helen Brittain replied that in PMID: 19181672, the patients present with weakness and a raised CK - this would make clinicians think of a muscular dystrophy primarily. Although technically it may be a myopathy, I think it is enough of a mimic to be included on both the dystrophy and myopathy panels. Therefore this gene should remain green on Congenital muscular dystrophy; to: In response to Zornitza Starks' review, Helen Brittain (Genomics England Clinical Fellow) was asked the following question: are the phenotypes of Reducing body myopathy, X-linked 1a, severe, infantile or early childhood onset (OMIM:300717) and/or Reducing body myopathy, X-linked 1b, with late childhood or adult onset (OMIM:300718), which are associated with FHL1 variants, appropriate for this panel - Congenital muscular dystrophy (R79)?
Helen Brittain replied that in PMID: 19181672, the patients present with weakness and a raised CK - this would make clinicians think of a muscular dystrophy primarily. Although technically it may be a myopathy, I think it is enough of a mimic to be included on both the dystrophy and myopathy panels. Therefore this gene should remain green on Congenital muscular dystrophy
Cleidocranial Dysplasia v1.1 CBFB Alistair Pagnamenta gene: CBFB was added
gene: CBFB was added to Cleidocranial Dysplasia. Sources: Literature
Mode of inheritance for gene: CBFB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CBFB were set to PMID: 36241386
Phenotypes for gene: CBFB were set to cleidocranial dysplasia; dental anomalies such as supernumery teeth and eruption failure; developmental delay (variable); shortening of the distal phalanges
Penetrance for gene: CBFB were set to Complete
Review for gene: CBFB was set to GREEN
gene: CBFB was marked as current diagnostic
Added comment: Beyltjens et al describe 8 individuals from 5 families (ascertained via GeneMatcher) with cleidocranial dysplasia and rare severe consequence variants in CBFB. Previous analysis of RUNX2 had been negative. CBFB encodes the core-binding factor β subunit, which can interact with RUNX2 to form a heterodimeric transcription factor - so biologically was a good candidate gene, even before the Beyltjens et al study. Aware of data in 100kGP that supports this new gene-disease association.
Sources: Literature
Monogenic short stature v0.175 Achchuthan Shanmugasundram Panel status changed from public to internal
Monogenic short stature v0.174 Achchuthan Shanmugasundram Panel status changed from internal to public
Dilated and arrhythmogenic cardiomyopathy v2.25 PRDM16 Mike Spiller reviewed gene: PRDM16: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Autoinflammatory disorders v2.1 OGFRL1 Hannah Knight gene: OGFRL1 was added
gene: OGFRL1 was added to Autoinflammatory disorders. Sources: Literature
Mode of inheritance for gene: OGFRL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OGFRL1 were set to PMID: 38699440
Phenotypes for gene: OGFRL1 were set to Cherubism
Review for gene: OGFRL1 was set to AMBER
Added comment: PMID: 38699440 (2024) identified two different homozygous LOF mutations in two unrelated families with cherubism. Functional work carried out, but inconclusive - mouse model did not recapitulate human cherubism
Sources: Literature
Adult onset hereditary spastic paraplegia v4.3 SPG7 Sarah Leigh changed review comment from: The mode of inheritance of this gene has been updated to SPG7 following NHS Genomic Medicine Service approval.; to: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal, following NHS Genomic Medicine Service approval.
Adult onset hereditary spastic paraplegia v4.3 SPG7 Sarah Leigh changed review comment from: The mode of inheritance of this gene has been updated to XX following NHS Genomic Medicine Service approval.; to: The mode of inheritance of this gene has been updated to SPG7 following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v4.11 RTN2 Sarah Leigh Tag Q2_24_NHS_review tag was added to gene: RTN2.
Hereditary neuropathy or pain disorder v4.11 SPTBN4 Sarah Leigh Tag Q2_24_promote_green was removed from gene: SPTBN4.
Tag Q2_24_NHS_review was removed from gene: SPTBN4.
Hereditary neuropathy or pain disorder v4.11 ABHD12 Sarah Leigh Tag Q2_24_promote_green tag was added to gene: ABHD12.
Tag Q2_24_NHS_review tag was added to gene: ABHD12.
Hereditary neuropathy or pain disorder v4.11 AGXT Sarah Leigh Tag Q2_24_promote_green tag was added to gene: AGXT.
Tag Q2_24_NHS_review tag was added to gene: AGXT.
Hereditary neuropathy or pain disorder v4.11 APOA1 Sarah Leigh Tag Q2_24_promote_green tag was added to gene: APOA1.
Tag Q2_24_NHS_review tag was added to gene: APOA1.
Hereditary neuropathy or pain disorder v4.11 B4GALNT1 Sarah Leigh Tag Q2_24_promote_green tag was added to gene: B4GALNT1.
Tag Q2_24_NHS_review tag was added to gene: B4GALNT1.
Hereditary neuropathy or pain disorder v4.11 BCKDHB Sarah Leigh Tag Q2_24_promote_green tag was added to gene: BCKDHB.
Tag Q2_24_NHS_review tag was added to gene: BCKDHB.
Hereditary neuropathy or pain disorder v4.11 FXN Sarah Leigh Tag Q2_24_promote_green tag was added to gene: FXN.
Tag Q2_24_NHS_review tag was added to gene: FXN.
Hereditary neuropathy or pain disorder v4.11 GALC Sarah Leigh Tag Q2_24_promote_green tag was added to gene: GALC.
Tag Q2_24_NHS_review tag was added to gene: GALC.
Hereditary neuropathy or pain disorder v4.11 GBA2 Sarah Leigh Tag Q2_24_promote_green tag was added to gene: GBA2.
Tag Q2_24_NHS_review tag was added to gene: GBA2.
Hereditary neuropathy or pain disorder v4.11 IARS2 Sarah Leigh Tag Q2_24_promote_green tag was added to gene: IARS2.
Tag Q2_24_NHS_review tag was added to gene: IARS2.
Hereditary neuropathy or pain disorder v4.11 LYST Sarah Leigh Tag Q2_24_promote_green tag was added to gene: LYST.
Tag Q2_24_NHS_review tag was added to gene: LYST.
Hereditary neuropathy or pain disorder v4.11 MMACHC Sarah Leigh Tag Q2_24_promote_green tag was added to gene: MMACHC.
Tag Q2_24_NHS_review tag was added to gene: MMACHC.
Hereditary neuropathy or pain disorder v4.11 MTTP Sarah Leigh Tag Q2_24_promote_green tag was added to gene: MTTP.
Tag Q2_24_NHS_review tag was added to gene: MTTP.
Hereditary neuropathy or pain disorder v4.11 NAGA Sarah Leigh Tag Q2_24_promote_green tag was added to gene: NAGA.
Tag Q2_24_NHS_review tag was added to gene: NAGA.
Hereditary neuropathy or pain disorder v4.11 PDYN Sarah Leigh Tag Q2_24_promote_green tag was added to gene: PDYN.
Tag Q2_24_NHS_review tag was added to gene: PDYN.
Hereditary neuropathy or pain disorder v4.11 PEX10 Sarah Leigh Tag Q2_24_promote_green tag was added to gene: PEX10.
Tag Q2_24_NHS_review tag was added to gene: PEX10.
Hereditary neuropathy or pain disorder v4.11 PEX7 Sarah Leigh Tag Q2_24_promote_green tag was added to gene: PEX7.
Tag Q2_24_NHS_review tag was added to gene: PEX7.
Hereditary neuropathy or pain disorder v4.11 PLP1 Sarah Leigh Tag Q2_24_promote_green tag was added to gene: PLP1.
Tag Q2_24_NHS_review tag was added to gene: PLP1.
Hereditary neuropathy or pain disorder v4.11 PMM2 Sarah Leigh Tag Q2_24_promote_green tag was added to gene: PMM2.
Tag Q2_24_NHS_review tag was added to gene: PMM2.
Hereditary neuropathy or pain disorder v4.11 PNPLA6 Sarah Leigh Tag Q2_24_promote_green tag was added to gene: PNPLA6.
Tag Q2_24_NHS_review tag was added to gene: PNPLA6.
Hereditary neuropathy or pain disorder v4.11 POLR3A Sarah Leigh Tag Q2_24_promote_green tag was added to gene: POLR3A.
Tag Q2_24_NHS_review tag was added to gene: POLR3A.
Hereditary neuropathy or pain disorder v4.11 SACS Sarah Leigh Tag Q2_24_promote_green tag was added to gene: SACS.
Tag Q2_24_NHS_review tag was added to gene: SACS.
Hereditary neuropathy or pain disorder v4.11 SCARB2 Sarah Leigh Tag Q2_24_promote_green tag was added to gene: SCARB2.
Tag Q2_24_NHS_review tag was added to gene: SCARB2.
Hereditary neuropathy or pain disorder v4.11 SLC25A19 Sarah Leigh Tag Q2_24_promote_green tag was added to gene: SLC25A19.
Tag Q2_24_NHS_review tag was added to gene: SLC25A19.
Hereditary neuropathy or pain disorder v4.11 SPTBN4 Sarah Leigh Tag Q2_24_promote_green tag was added to gene: SPTBN4.
Tag Q2_24_NHS_review tag was added to gene: SPTBN4.
Hereditary neuropathy or pain disorder v4.11 SURF1 Sarah Leigh Tag Q2_24_promote_green tag was added to gene: SURF1.
Tag Q2_24_NHS_review tag was added to gene: SURF1.
Hereditary neuropathy or pain disorder v4.11 TYMP Sarah Leigh Tag Q2_24_promote_green tag was added to gene: TYMP.
Tag Q2_24_NHS_review tag was added to gene: TYMP.
Hereditary neuropathy or pain disorder v4.11 XK Sarah Leigh Tag Q2_24_promote_green tag was added to gene: XK.
Tag Q2_24_NHS_review tag was added to gene: XK.
Hereditary neuropathy or pain disorder v4.11 XK Sarah Leigh reviewed gene: XK: Rating: GREEN; Mode of pathogenicity: ; Publications: 8619554, 11261514; Phenotypes: McLeod syndrome, OMIM:300842; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Hereditary neuropathy or pain disorder v4.11 TYMP Sarah Leigh reviewed gene: TYMP: Rating: GREEN; Mode of pathogenicity: ; Publications: 14757860, 12177387, 9924029; Phenotypes: Mitochondrial DNA depletion syndrome 1 (MNGIE type), OMIM:603041; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 SURF1 Sarah Leigh reviewed gene: SURF1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Charcot-Marie-Tooth disease, type 4K, OMIM:616684, Mitochondrial complex IV deficiency, nuclear type 1, OMIM:220110; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 SPTBN4 Sarah Leigh edited their review of gene: SPTBN4: Added comment: At least six SPTBN4 variants have been associated with OMIM:617519, which includes axonal and demyelinating peripheral neuropathy as one of the clinical features. Six SPTBN4 variants have been reported by PMID: 28540413;29861105 in five unrelated cases of OMIM:617519.; Changed rating: GREEN; Changed publications to: 28540413, 29861105; Changed phenotypes to: Neurodevelopmental disorder with hypotonia, neuropathy, and deafness, OMIM:617519; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 SLC25A19 Sarah Leigh reviewed gene: SLC25A19: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Thiamine metabolism dysfunction syndrome 4 (progressive polyneuropathy type), OMIM:613710; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 SCARB2 Sarah Leigh reviewed gene: SCARB2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Epilepsy, progressive myoclonic 4, with or without renal failure, OMIM:254900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 SACS Sarah Leigh reviewed gene: SACS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Spastic ataxia, Charlevoix-Saguenay type, OMIM:270550; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 POLR3A Sarah Leigh reviewed gene: POLR3A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Wiedemann-Rautenstrauch syndrome, OMIM:264090, Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism OMIM:607694; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 PNPLA6 Sarah Leigh reviewed gene: PNPLA6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Oliver-McFarlane syndrome, OMIM:275400, Spastic paraplegia 39, autosomal recessive, OMIM:612020, Boucher-Neuhauser syndrome, OMIM:215470; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 PMM2 Sarah Leigh reviewed gene: PMM2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Congenital disorder of glycosylation, type Ia, OMIM:212065; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 PLP1 Sarah Leigh reviewed gene: PLP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Spastic paraplegia 2, X-linked, OMIM:312920, Pelizaeus-Merzbacher disease, OMIM:312080; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Hereditary neuropathy or pain disorder v4.11 PEX7 Sarah Leigh reviewed gene: PEX7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Peroxisome biogenesis disorder 9B, OMIM:14879; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 PEX10 Sarah Leigh reviewed gene: PEX10: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Peroxisome biogenesis disorder 6A (Zellweger), OMIM:614870, Peroxisome biogenesis disorder 6B, OMIM:614871; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 PDYN Sarah Leigh reviewed gene: PDYN: Rating: GREEN; Mode of pathogenicity: ; Publications: 21035104; Phenotypes: Spinocerebellar ataxia 23, OMIM:610245; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v4.11 NAGA Sarah Leigh reviewed gene: NAGA: Rating: GREEN; Mode of pathogenicity: ; Publications: 8782044, 11251574; Phenotypes: Kanzaki disease, OMIM:609242; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 MTTP Sarah Leigh reviewed gene: MTTP: Rating: GREEN; Mode of pathogenicity: ; Publications: 8361539, 10446076, 8111381; Phenotypes: Abetalipoproteinemia, OMIM:200100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 MMACHC Sarah Leigh reviewed gene: MMACHC: Rating: GREEN; Mode of pathogenicity: ; Publications: 17431913, 16311595, 19370762; Phenotypes: Methylmalonic aciduria and homocystinuria, cblC type, OMIM:277400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 LYST Sarah Leigh reviewed gene: LYST: Rating: GREEN; Mode of pathogenicity: ; Publications: 9215680, 8896560, 9215679, 11857544; Phenotypes: Chediak-Higashi syndrome, OMIM:214500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 IARS2 Sarah Leigh reviewed gene: IARS2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia, OMIM:616007; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 GBA2 Sarah Leigh reviewed gene: GBA2: Rating: GREEN; Mode of pathogenicity: ; Publications: 24252062, 23332917, 23332916; Phenotypes: Spastic paraplegia 46, autosomal recessive, OMIM:614409; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 GALC Sarah Leigh reviewed gene: GALC: Rating: GREEN; Mode of pathogenicity: ; Publications: 20886637, 21070211; Phenotypes: Krabbe disease, OMIM:245200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 FXN Sarah Leigh reviewed gene: FXN: Rating: GREEN; Mode of pathogenicity: ; Publications: 21830088, 9737785, 8596916; Phenotypes: Friedreich ataxia, OMIM:229300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 BCKDHB Sarah Leigh reviewed gene: BCKDHB: Rating: GREEN; Mode of pathogenicity: ; Publications: 14742428, 2022752, 11509994; Phenotypes: Maple syrup urine disease, type Ib,OMIM:620698; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 B4GALNT1 Sarah Leigh reviewed gene: B4GALNT1: Rating: GREEN; Mode of pathogenicity: ; Publications: 23746551; Phenotypes: Spastic paraplegia 26, autosomal recessive, OMIM:609195; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 APOA1 Sarah Leigh reviewed gene: APOA1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Amyloidosis, 3 or more types, OMIM:105200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v4.11 AGXT Sarah Leigh reviewed gene: AGXT: Rating: GREEN; Mode of pathogenicity: ; Publications: 1961759, 10960483, 15464418; Phenotypes: Hyperoxaluria, primary, type 1, OMIM:259900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 ABHD12 Sarah Leigh reviewed gene: ABHD12: Rating: GREEN; Mode of pathogenicity: ; Publications: 20797687, 24697911; Phenotypes: Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract, OMIM:612674; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Adult onset hereditary spastic paraplegia v4.3 SPG7 Eleanor Williams Tag Q2_23_MOI was removed from gene: SPG7.
Hereditary neuropathy or pain disorder v4.10 SLC12A6 Eleanor Williams Tag for-review was removed from gene: SLC12A6.
Tag to_be_confirmed_NHSE was removed from gene: SLC12A6.
Tag Q4_23_promote_green was removed from gene: SLC12A6.
Tag Q4_23_NHS_review was removed from gene: SLC12A6.
Intellectual disability v6.13 ZBTB47 Eleanor Williams Tag gene-checked tag was added to gene: ZBTB47.
Intellectual disability v6.13 KDM5A Eleanor Williams Phenotypes for gene: KDM5A were changed from autism spectrum disorder, MONDO:0005258; intellectual disability, MONDO:0001071 to autism spectrum disorder, MONDO:0005258; intellectual disability, MONDO:0001071; El Hayek-Chahrour neurodevelopmental syndrome, OMIM:620820
Intellectual disability v6.12 KDM5A Eleanor Williams Tag gene-checked was removed from gene: KDM5A.
Monogenic short stature v0.173 Eleanor Williams Panel status changed from public to internal
Monogenic short stature v0.172 Eleanor Williams Panel status changed from internal to public
Early onset or syndromic epilepsy v5.10 ZBTB47 Eleanor Williams Tag gene-checked tag was added to gene: ZBTB47.
Intellectual disability v6.12 TMEM63B Eleanor Williams Tag gene-checked tag was added to gene: TMEM63B.
Early onset or syndromic epilepsy v5.10 TMEM63B Eleanor Williams Tag gene-checked tag was added to gene: TMEM63B.
Childhood onset dystonia, chorea or related movement disorder v4.3 TMEM151A Eleanor Williams Tag gene-checked tag was added to gene: TMEM151A.
Ataxia and cerebellar anomalies - narrow panel v5.3 THG1L Eleanor Williams Tag gene-checked tag was added to gene: THG1L.
Intellectual disability v6.12 PPP1R3F Eleanor Williams Tag gene-checked tag was added to gene: PPP1R3F.
Early onset or syndromic epilepsy v5.10 PPP1R3F Eleanor Williams Tag gene-checked tag was added to gene: PPP1R3F.
Intellectual disability v6.12 MAST4 Eleanor Williams Tag gene-checked tag was added to gene: MAST4.
Early onset or syndromic epilepsy v5.10 MAST4 Eleanor Williams Tag gene-checked tag was added to gene: MAST4.
Retinal disorders v5.4 CFAP20 Eleanor Williams Tag gene-checked tag was added to gene: CFAP20.
Paediatric or syndromic cardiomyopathy v4.3 CAP2 Eleanor Williams Tag gene-checked tag was added to gene: CAP2.
Early onset or syndromic epilepsy v5.10 RAB5C Eleanor Williams Tag gene-checked tag was added to gene: RAB5C.
Intellectual disability v6.12 RAB5C Eleanor Williams Tag gene-checked tag was added to gene: RAB5C.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 PTPN2 Eleanor Williams Tag gene-checked tag was added to gene: PTPN2.
Intellectual disability v6.12 PABPC1 Eleanor Williams Tag gene-checked tag was added to gene: PABPC1.
Early onset or syndromic epilepsy v5.10 PABPC1 Eleanor Williams Tag gene-checked tag was added to gene: PABPC1.
Neonatal diabetes v4.6 ONECUT1 Eleanor Williams Tag gene-checked tag was added to gene: ONECUT1.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 NFAT5 Eleanor Williams Tag gene-checked tag was added to gene: NFAT5.
Intellectual disability v6.12 MYH10 Eleanor Williams Tag gene-checked tag was added to gene: MYH10.
Inherited polyposis and early onset colorectal cancer - germline testing v2.11 GREM1 Eleanor Williams Tag gene-checked tag was added to gene: GREM1.
Lipodystrophy - childhood onset v4.52 EPHX1 Eleanor Williams Tag gene-checked tag was added to gene: EPHX1.
Adult onset neurodegenerative disorder v5.3 DNAJC7 Eleanor Williams Tag gene-checked tag was added to gene: DNAJC7.
Adult onset neurodegenerative disorder v5.3 DNAJC7 Eleanor Williams reviewed gene: DNAJC7: Rating: ; Mode of pathogenicity: None; Publications: 31768050, 35039179, 34233860, 32897108, 37870677, 35456894; Phenotypes: ; Mode of inheritance: None
Hereditary neuropathy or pain disorder v4.10 DHX9 Eleanor Williams Tag gene-checked tag was added to gene: DHX9.
Intellectual disability v6.12 DHX9 Eleanor Williams Tag gene-checked tag was added to gene: DHX9.
Intellectual disability v6.12 CNOT9 Eleanor Williams Tag gene-checked tag was added to gene: CNOT9.
Early onset or syndromic epilepsy v5.10 CNOT9 Eleanor Williams Tag gene-checked tag was added to gene: CNOT9.
Unexplained young onset end-stage renal disease v4.3 CFHR2 Eleanor Williams Tag gene-checked tag was added to gene: CFHR2.
Intellectual disability v6.12 CDK16 Eleanor Williams Tag gene-checked tag was added to gene: CDK16.
Structural eye disease v3.79 ARHGAP35 Eleanor Williams Tag gene-checked tag was added to gene: ARHGAP35.
Intellectual disability v6.12 ARF3 Eleanor Williams Tag gene-checked tag was added to gene: ARF3.
Early onset or syndromic epilepsy v5.10 ARF3 Eleanor Williams Tag gene-checked tag was added to gene: ARF3.
Severe microcephaly v5.7 ARF3 Eleanor Williams Tag gene-checked tag was added to gene: ARF3.
Clefting v5.3 AMOTL1 Eleanor Williams Tag gene-checked tag was added to gene: AMOTL1.
Likely inborn error of metabolism v5.3 ATP5E Eleanor Williams Tag new-gene-name tag was added to gene: ATP5E.
Monogenic short stature v0.171 Eleanor Williams Panel status changed from public to internal
Hereditary neuropathy or pain disorder v4.10 SLC12A6 Eleanor Williams commented on gene: SLC12A6
Hereditary neuropathy or pain disorder v4.10 SLC12A6 Eleanor Williams Mode of inheritance for gene: SLC12A6 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Monogenic short stature v0.170 Eleanor Williams Panel status changed from internal to public
Hereditary neuropathy or pain disorder v4.9 SURF1 Sarah Leigh Publications for gene: SURF1 were set to
Intellectual disability v6.12 MAST3 Sarah Leigh Tag Q2_24_NHS_review tag was added to gene: MAST3.
Early onset or syndromic epilepsy v5.10 MAST3 Sarah Leigh Tag Q2_24_NHS_review tag was added to gene: MAST3.
Intellectual disability v6.12 MAST3 Sarah Leigh Tag Q2_24_MOI was removed from gene: MAST3.
Intellectual disability v6.12 MAST3 Sarah Leigh Entity copied from Early onset or syndromic epilepsy v5.10
Intellectual disability v6.12 MAST3 Sarah Leigh gene: MAST3 was added
gene: MAST3 was added to Intellectual disability. Sources: Expert Review Amber,Literature
Q2_24_promote_green, Q2_24_MOI tags were added to gene: MAST3.
Mode of inheritance for gene: MAST3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MAST3 were set to 34185323; 35095415
Mode of pathogenicity for gene: MAST3 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Early onset or syndromic epilepsy v5.10 MAST3 Sarah Leigh changed review comment from: MAST3 variants have been associated with Developmental and epileptic encephalopathy 108 (OMIM:620115). PMID:34185323 reports five de novo missense MAST3 variants in eleven unrelated individuals with developmental and epileptic encephalopathy, with a range of seizure types. Functional studies suggest that the MAST3 variants have a gain-of-function effect.
Sources: Literature; to: MAST3 variants have been associated with Developmental and epileptic encephalopathy 108 (OMIM:620115). PMID:34185323 reports five de novo missense MAST3 variants in eleven unrelated individuals with developmental and epileptic encephalopathy, with a range of seizure types. These variants are within the serine-threonine kinases (STK) domain. PMID: 35095415 reports a further four de novo missense MAST3 variants, within the domain of unknown function (DUF). It would appear that the variants within the STK domain are associated with a neurodevelopmental disorder with a epilepsy phenotype, while variants within the DUF domain have a autistic spectrum disorder phenotype (PMID: 35095415)
Functional studies suggest that the MAST3 variants have a gain-of-function effect (PMID:34185323; 35095415).
Early onset or syndromic epilepsy v5.10 MAST3 Sarah Leigh Publications for gene: MAST3 were set to 34185323
Early onset or syndromic epilepsy v5.9 MAST3 Sarah Leigh Added comment: Comment on mode of pathogenicity: It would appear that MAST3 variants have a gain-of-function effect (PMID:34185323).
Early onset or syndromic epilepsy v5.9 MAST3 Sarah Leigh Mode of pathogenicity for gene: MAST3 was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Early onset or syndromic epilepsy v5.8 MAST3 Sarah Leigh Classified gene: MAST3 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v5.8 MAST3 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Early onset or syndromic epilepsy v5.8 MAST3 Sarah Leigh Gene: mast3 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v5.7 MAST3 Sarah Leigh Tag Q2_24_promote_green tag was added to gene: MAST3.
Tag Q2_24_MOI tag was added to gene: MAST3.
Early onset or syndromic epilepsy v5.7 MAST3 Sarah Leigh gene: MAST3 was added
gene: MAST3 was added to Early onset or syndromic epilepsy. Sources: Literature
Mode of inheritance for gene: MAST3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MAST3 were set to 34185323
Mode of pathogenicity for gene: MAST3 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: MAST3 was set to GREEN
Added comment: MAST3 variants have been associated with Developmental and epileptic encephalopathy 108 (OMIM:620115). PMID:34185323 reports five de novo missense MAST3 variants in eleven unrelated individuals with developmental and epileptic encephalopathy, with a range of seizure types. Functional studies suggest that the MAST3 variants have a gain-of-function effect.
Sources: Literature
Paediatric or syndromic cardiomyopathy v4.3 NEXN Hannah Robinson reviewed gene: NEXN: Rating: ; Mode of pathogenicity: None; Publications: 35166435, 33949776, 33027564, 32058062; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Limb disorders v5.4 FBXW11 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 SLC5A6 Eleanor Williams changed review comment from: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remainsred.; to: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains red.
Early onset or syndromic epilepsy v5.6 ZBTB47 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 U2AF2 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 TRIT1 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 TMEM63B Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 SHQ1 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 SHQ1 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated togreenand the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 SCN8A Eleanor Williams changed review comment from: The mode of inheritance of this gene has been updated to'BOTH monoallelic and biallelic, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 RAB5C Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 PTCD3 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 PPP1R3F Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'X-LINKED: hemizygous mutation in males, biallelic mutations in females'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'X-LINKED: hemizygous mutation in males, biallelic mutations in females' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 PLA2G6 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 PIP5K1C Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 PIGM Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 PABPC1 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'BOTH monoallelic and biallelic, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 MAST4 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 LETM1 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 KDM6B Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 KCNH5 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 HECTD4 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 ESAM Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 EIF4A2 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'BOTH monoallelic and biallelic, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 DNAJC6 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 CRELD1 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 ATP6V0C Eleanor Williams changed review comment from: The rating of this gene has been updated to green and the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 ASL Eleanor Williams changed review comment from: The rating of this gene has been updated to green and the mode of inheritance set to'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 ARF3 Eleanor Williams changed review comment from: The rating of this gene has been updated to green and the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown' following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 AGO1 Eleanor Williams changed review comment from: The rating of this gene has been updated to green and the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown' following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 CNOT9 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 ATP6V0C Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 ASL Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 ARF3 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 AGO1 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 CACNB4 Eleanor Williams edited their review of gene: CACNB4: Changed rating: RED
Early onset or syndromic epilepsy v5.6 CACNB4 Eleanor Williams changed review comment from: The rating of this gene has been updated from green to redfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated from green to red following NHS Genomic Medicine Service approval.
Childhood onset hereditary spastic paraplegia v5.3 RETREG1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: RETREG1.
Tag Q4_23_NHS_review was removed from gene: RETREG1.
Childhood onset hereditary spastic paraplegia v5.3 RETREG1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Childhood onset hereditary spastic paraplegia v5.3 PPFIBP1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Childhood onset hereditary spastic paraplegia v5.3 PPFIBP1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: PPFIBP1.
Childhood onset hereditary spastic paraplegia v5.3 HECTD4 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: HECTD4.
Childhood onset hereditary spastic paraplegia v5.3 HECTD4 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Childhood onset hereditary spastic paraplegia v5.3 CLDN11 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CLDN11.
Childhood onset hereditary spastic paraplegia v5.3 CLDN11 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.
Childhood onset hereditary spastic paraplegia v5.3 UCHL1 Achchuthan Shanmugasundram Tag Q3_23_MOI was removed from gene: UCHL1.
Childhood onset hereditary spastic paraplegia v5.3 UCHL1 Achchuthan Shanmugasundram changed review comment from: The mode of inheritance of this gene has been updated toBOTH monoallelic and biallelic, autosomal or pseudoautosomalfollowing NHS Genomic Medicine Service approval.; to: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Childhood onset hereditary spastic paraplegia v5.3 LETM1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Childhood onset hereditary spastic paraplegia v5.3 LETM1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: LETM1.
Tag Q3_23_MOI was removed from gene: LETM1.
Childhood onset hereditary spastic paraplegia v5.3 AMFR Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: AMFR.
Childhood onset hereditary spastic paraplegia v5.3 AMFR Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Childhood onset hereditary spastic paraplegia v5.3 UCHL1 Achchuthan Shanmugasundram reviewed gene: UCHL1: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia v5.3 RETREG1 Achchuthan Shanmugasundram commented on gene: RETREG1: The rating of this gene has been updated togreenand the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.
Childhood onset hereditary spastic paraplegia v5.3 PPFIBP1 Achchuthan Shanmugasundram commented on gene: PPFIBP1: The rating of this gene has been updated togreenand the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.
Childhood onset hereditary spastic paraplegia v5.3 LETM1 Achchuthan Shanmugasundram reviewed gene: LETM1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia v5.3 HECTD4 Achchuthan Shanmugasundram commented on gene: HECTD4: The rating of this gene has been updated togreenand the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.
Childhood onset hereditary spastic paraplegia v5.3 CLDN11 Achchuthan Shanmugasundram commented on gene: CLDN11: The rating of this gene has been updated togreenand the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.
Childhood onset hereditary spastic paraplegia v5.3 AMFR Achchuthan Shanmugasundram commented on gene: AMFR: The rating of this gene has been updated togreenand the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.
Childhood onset hereditary spastic paraplegia v5.2 UCHL1 Achchuthan Shanmugasundram Mode of inheritance for gene UCHL1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia v5.2 RETREG1 Achchuthan Shanmugasundram Source Expert Review Green was added to RETREG1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset hereditary spastic paraplegia v5.2 PPFIBP1 Achchuthan Shanmugasundram Source NHS GMS was added to PPFIBP1.
Source Expert Review Green was added to PPFIBP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset hereditary spastic paraplegia v5.2 LETM1 Achchuthan Shanmugasundram Source NHS GMS was added to LETM1.
Source Expert Review Green was added to LETM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset hereditary spastic paraplegia v5.2 HECTD4 Achchuthan Shanmugasundram Source Expert Review Green was added to HECTD4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset hereditary spastic paraplegia v5.2 CLDN11 Achchuthan Shanmugasundram Source NHS GMS was added to CLDN11.
Source Expert Review Green was added to CLDN11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset hereditary spastic paraplegia v5.2 AMFR Achchuthan Shanmugasundram Source NHS GMS was added to AMFR.
Source Expert Review Green was added to AMFR.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v4.3 AFG3L2 Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE was removed from gene: AFG3L2.
Childhood onset dystonia, chorea or related movement disorder v4.3 AFG3L2 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated from green toamberfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated from green to amber following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v4.3 SHQ1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SHQ1.
Childhood onset dystonia, chorea or related movement disorder v4.3 SHQ1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v4.3 ASL Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ASL.
Tag Q4_23_NHS_review was removed from gene: ASL.
Childhood onset dystonia, chorea or related movement disorder v4.3 ASL Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v4.3 ARX Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ARX.
Childhood onset dystonia, chorea or related movement disorder v4.3 ARX Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v4.3 OCLN Achchuthan Shanmugasundram Tag Q3_23_expert_review was removed from gene: OCLN.
Tag Q3_23_demote_red was removed from gene: OCLN.
Childhood onset dystonia, chorea or related movement disorder v4.3 OCLN Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated from green toredfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated from green to red following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v4.3 TSPOAP1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: TSPOAP1.
Childhood onset dystonia, chorea or related movement disorder v4.3 TSPOAP1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v4.3 TMEM151A Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v4.3 TMEM151A Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: TMEM151A.
Tag Q3_23_NHS_review was removed from gene: TMEM151A.
Childhood onset dystonia, chorea or related movement disorder v4.3 TBC1D24 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: TBC1D24.
Childhood onset dystonia, chorea or related movement disorder v4.3 TBC1D24 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v4.3 SYT1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: SYT1.
Childhood onset dystonia, chorea or related movement disorder v4.3 SYT1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v4.3 SQSTM1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: SQSTM1.
Childhood onset dystonia, chorea or related movement disorder v4.3 SQSTM1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v4.3 SLC30A9 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: SLC30A9.
Childhood onset dystonia, chorea or related movement disorder v4.3 SLC30A9 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v4.3 SLC18A2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: SLC18A2.
Childhood onset dystonia, chorea or related movement disorder v4.3 SLC18A2 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v4.3 L2HGDH Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: L2HGDH.
Childhood onset dystonia, chorea or related movement disorder v4.3 L2HGDH Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v4.3 KCNQ2 Achchuthan Shanmugasundram Tag Q3_23_expert_review was removed from gene: KCNQ2.
Tag Q3_23_demote_red was removed from gene: KCNQ2.
Childhood onset dystonia, chorea or related movement disorder v4.3 DNAJC6 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: DNAJC6.
Childhood onset dystonia, chorea or related movement disorder v4.3 DNAJC6 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v4.3 KCNQ2 Achchuthan Shanmugasundram commented on gene: KCNQ2
Childhood onset dystonia, chorea or related movement disorder v4.3 TSPOAP1 Achchuthan Shanmugasundram reviewed gene: TSPOAP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder v4.3 TMEM151A Achchuthan Shanmugasundram commented on gene: TMEM151A: The rating of this gene has been updated togreenand the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v4.3 TBC1D24 Achchuthan Shanmugasundram commented on gene: TBC1D24: The rating of this gene has been updated togreenand the mode of inheritance set to'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v4.3 SYT1 Achchuthan Shanmugasundram commented on gene: SYT1: The rating of this gene has been updated togreenand the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v4.3 SQSTM1 Achchuthan Shanmugasundram commented on gene: SQSTM1: The rating of this gene has been updated togreenand the mode of inheritance set to'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v4.3 SLC30A9 Achchuthan Shanmugasundram commented on gene: SLC30A9: The rating of this gene has been updated togreenand the mode of inheritance set to'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v4.3 SLC18A2 Achchuthan Shanmugasundram commented on gene: SLC18A2: The rating of this gene has been updated togreenand the mode of inheritance set to'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v4.3 SHQ1 Achchuthan Shanmugasundram reviewed gene: SHQ1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder v4.3 OCLN Achchuthan Shanmugasundram reviewed gene: OCLN: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Childhood onset dystonia, chorea or related movement disorder v4.3 L2HGDH Achchuthan Shanmugasundram commented on gene: L2HGDH: The rating of this gene has been updated togreenand the mode of inheritance set to'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v4.3 DNAJC6 Achchuthan Shanmugasundram reviewed gene: DNAJC6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder v4.3 ASL Achchuthan Shanmugasundram reviewed gene: ASL: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder v4.3 ARX Achchuthan Shanmugasundram reviewed gene: ARX: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Childhood onset dystonia, chorea or related movement disorder v4.3 AFG3L2 Achchuthan Shanmugasundram reviewed gene: AFG3L2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Childhood onset dystonia, chorea or related movement disorder v4.2 TSPOAP1 Achchuthan Shanmugasundram Source Expert Review Green was added to TSPOAP1.
Source NHS GMS was added to TSPOAP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v4.2 TMEM151A Achchuthan Shanmugasundram Source Expert Review Green was added to TMEM151A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v4.2 TBC1D24 Achchuthan Shanmugasundram Source Expert Review Green was added to TBC1D24.
Source NHS GMS was added to TBC1D24.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v4.2 SYT1 Achchuthan Shanmugasundram Source Expert Review Green was added to SYT1.
Source NHS GMS was added to SYT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v4.2 SQSTM1 Achchuthan Shanmugasundram Source Expert Review Green was added to SQSTM1.
Source NHS GMS was added to SQSTM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v4.2 SLC30A9 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC30A9.
Source NHS GMS was added to SLC30A9.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v4.2 SLC18A2 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC18A2.
Source NHS GMS was added to SLC18A2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v4.2 SHQ1 Achchuthan Shanmugasundram Source Expert Review Green was added to SHQ1.
Source NHS GMS was added to SHQ1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v4.2 OCLN Achchuthan Shanmugasundram Source Expert Review Red was added to OCLN.
Source NHS GMS was added to OCLN.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Childhood onset dystonia, chorea or related movement disorder v4.2 L2HGDH Achchuthan Shanmugasundram Source Expert Review Green was added to L2HGDH.
Source NHS GMS was added to L2HGDH.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v4.2 DNAJC6 Achchuthan Shanmugasundram Source Expert Review Green was added to DNAJC6.
Source NHS GMS was added to DNAJC6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v4.2 ASL Achchuthan Shanmugasundram Source Expert Review Green was added to ASL.
Source NHS GMS was added to ASL.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v4.2 ARX Achchuthan Shanmugasundram Source Expert Review Green was added to ARX.
Source NHS GMS was added to ARX.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v4.2 AFG3L2 Achchuthan Shanmugasundram Source NHS GMS was added to AFG3L2.
Source Expert Review Amber was added to AFG3L2.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Arthrogryposis v6.3 ACTC1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ACTC1.
Arthrogryposis v6.3 ACTC1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.
Arthrogryposis v6.3 ACTC1 Achchuthan Shanmugasundram commented on gene: ACTC1: The rating of this gene has been updated togreenand the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.
Arthrogryposis v6.2 ACTC1 Achchuthan Shanmugasundram Source NHS GMS was added to ACTC1.
Source Expert Review Green was added to ACTC1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset leukodystrophy v4.3 RNASET2 Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE was removed from gene: RNASET2.
Adult onset leukodystrophy v4.3 RNASET2 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toamberfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to amber following NHS Genomic Medicine Service approval.
Adult onset leukodystrophy v4.3 POLR1C Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE was removed from gene: POLR1C.
Adult onset leukodystrophy v4.3 POLR1C Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toamberfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to amber following NHS Genomic Medicine Service approval.
Adult onset leukodystrophy v4.3 MARS Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE was removed from gene: MARS.
Adult onset leukodystrophy v4.3 MARS Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toamberfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to amber following NHS Genomic Medicine Service approval.
Adult onset leukodystrophy v4.3 COL4A2 Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE was removed from gene: COL4A2.
Adult onset leukodystrophy v4.3 AARS Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE was removed from gene: AARS.
Adult onset leukodystrophy v4.3 OCRL Achchuthan Shanmugasundram Tag Q4_23_demote_amber was removed from gene: OCRL.
Tag Q4_23_expert_review was removed from gene: OCRL.
Adult onset leukodystrophy v4.3 OCRL Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toamberfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to amber following NHS Genomic Medicine Service approval.
Adult onset leukodystrophy v4.3 HMGCL Achchuthan Shanmugasundram Tag Q4_23_demote_amber was removed from gene: HMGCL.
Tag Q4_23_expert_review was removed from gene: HMGCL.
Adult onset leukodystrophy v4.3 HMGCL Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toamberfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to amber following NHS Genomic Medicine Service approval.
Adult onset leukodystrophy v4.3 RPS6KA3 Achchuthan Shanmugasundram Tag Q3_23_expert_review was removed from gene: RPS6KA3.
Tag Q3_23_demote_red was removed from gene: RPS6KA3.
Adult onset leukodystrophy v4.3 RPS6KA3 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toredfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to red following NHS Genomic Medicine Service approval.
Adult onset leukodystrophy v4.3 RNF216 Achchuthan Shanmugasundram Tag Q3_23_expert_review was removed from gene: RNF216.
Tag Q3_23_demote_amber was removed from gene: RNF216.
Adult onset leukodystrophy v4.3 GCDH Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: GCDH.
Tag Q3_23_MOI was removed from gene: GCDH.
Adult onset leukodystrophy v4.3 GCDH Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated to greenand the mode of inheritance set to'BOTH monoallelic and biallelic, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Adult onset neurodegenerative disorder v5.3 DNAJC7 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: DNAJC7.
Adult onset neurodegenerative disorder v5.3 GBA Achchuthan Shanmugasundram reviewed gene: GBA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Adult onset neurodegenerative disorder v5.3 DNAJC7 Achchuthan Shanmugasundram reviewed gene: DNAJC7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Adult onset leukodystrophy v4.3 RPS6KA3 Achchuthan Shanmugasundram reviewed gene: RPS6KA3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v4.3 RNF216 Achchuthan Shanmugasundram commented on gene: RNF216
Adult onset leukodystrophy v4.3 RNASET2 Achchuthan Shanmugasundram reviewed gene: RNASET2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v4.3 POLR1C Achchuthan Shanmugasundram reviewed gene: POLR1C: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v4.3 OCRL Achchuthan Shanmugasundram reviewed gene: OCRL: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v4.3 MARS Achchuthan Shanmugasundram reviewed gene: MARS: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v4.3 HMGCL Achchuthan Shanmugasundram reviewed gene: HMGCL: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v4.3 COL4A2 Achchuthan Shanmugasundram commented on gene: COL4A2
Adult onset leukodystrophy v4.3 AARS Achchuthan Shanmugasundram commented on gene: AARS
Adult onset leukodystrophy v4.3 GCDH Achchuthan Shanmugasundram reviewed gene: GCDH: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Adult onset neurodegenerative disorder v5.2 GBA Achchuthan Shanmugasundram Source Expert Review Green was added to GBA.
Mode of inheritance for gene GBA was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset neurodegenerative disorder v5.2 DNAJC7 Achchuthan Shanmugasundram Source NHS GMS was added to DNAJC7.
Source Expert Review Green was added to DNAJC7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset leukodystrophy v4.2 RPS6KA3 Achchuthan Shanmugasundram Source Expert Review Red was added to RPS6KA3.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset leukodystrophy v4.2 RNASET2 Achchuthan Shanmugasundram Source Expert Review Amber was added to RNASET2.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Adult onset leukodystrophy v4.2 POLR1C Achchuthan Shanmugasundram Source Expert Review Amber was added to POLR1C.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Adult onset leukodystrophy v4.2 OCRL Achchuthan Shanmugasundram Source Expert Review Amber was added to OCRL.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Adult onset leukodystrophy v4.2 MARS Achchuthan Shanmugasundram Source Expert Review Amber was added to MARS.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Adult onset leukodystrophy v4.2 HMGCL Achchuthan Shanmugasundram Source Expert Review Amber was added to HMGCL.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Adult onset leukodystrophy v4.2 GCDH Achchuthan Shanmugasundram Source NHS GMS was added to GCDH.
Source Expert Review Green was added to GCDH.
Mode of inheritance for gene GCDH was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset hereditary spastic paraplegia v4.3 UCHL1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: UCHL1.
Tag Q3_23_MOI was removed from gene: UCHL1.
Adult onset hereditary spastic paraplegia v4.3 UCHL1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'BOTH monoallelic and biallelic, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Adult onset hereditary spastic paraplegia v4.3 PRNP Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PRNP.
Adult onset hereditary spastic paraplegia v4.3 PRNP Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.
Adult onset hereditary spastic paraplegia v4.3 AP4S1 Achchuthan Shanmugasundram Tag for-review was removed from gene: AP4S1.
Tag to_be_confirmed_NHSE was removed from gene: AP4S1.
Adult onset hereditary spastic paraplegia v4.3 AP4S1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toamberfollowing NHS Genomic Medicine Service approval. The associated phenotype has childhood onset.; to: The rating of this gene has been updated to amber following NHS Genomic Medicine Service approval. The associated phenotype has childhood onset.
Adult onset hereditary spastic paraplegia v4.3 AP4M1 Achchuthan Shanmugasundram Tag for-review was removed from gene: AP4M1.
Tag to_be_confirmed_NHSE was removed from gene: AP4M1.
Adult onset hereditary spastic paraplegia v4.3 AP4M1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toamberfollowing NHS Genomic Medicine Service approval. The associated phenotype has childhood onset.; to: The rating of this gene has been updated to amber following NHS Genomic Medicine Service approval. The associated phenotype has childhood onset.
Adult onset hereditary spastic paraplegia v4.3 AP4B1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated to amber following NHS Genomic Medicine Service approval. The associated phenotype has childhood onset.; to: The rating of this gene has been updated to amber following NHS Genomic Medicine Service approval. The associated phenotype has childhood onset.
Adult onset hereditary spastic paraplegia v4.3 AP4E1 Achchuthan Shanmugasundram Tag for-review was removed from gene: AP4E1.
Tag to_be_confirmed_NHSE was removed from gene: AP4E1.
Adult onset hereditary spastic paraplegia v4.3 AP4E1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toamberfollowing NHS Genomic Medicine Service approval. The associated phenotype has childhood onset.; to: The rating of this gene has been updated to amber following NHS Genomic Medicine Service approval. The associated phenotype has childhood onset.
Adult onset hereditary spastic paraplegia v4.3 AP4B1 Achchuthan Shanmugasundram Tag for-review was removed from gene: AP4B1.
Tag to_be_confirmed_NHSE was removed from gene: AP4B1.
Adult onset hereditary spastic paraplegia v4.3 AP4B1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toamberfollowing NHS Genomic Medicine Service approval. The associated phenotype has childhood onset.; to: The rating of this gene has been updated to amber following NHS Genomic Medicine Service approval. The associated phenotype has childhood onset.
Adult onset hereditary spastic paraplegia v4.3 UCHL1 Achchuthan Shanmugasundram reviewed gene: UCHL1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Adult onset hereditary spastic paraplegia v4.3 PRNP Achchuthan Shanmugasundram reviewed gene: PRNP: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Adult onset hereditary spastic paraplegia v4.3 AP4S1 Achchuthan Shanmugasundram reviewed gene: AP4S1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset hereditary spastic paraplegia v4.3 AP4M1 Achchuthan Shanmugasundram reviewed gene: AP4M1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset hereditary spastic paraplegia v4.3 AP4E1 Achchuthan Shanmugasundram reviewed gene: AP4E1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset hereditary spastic paraplegia v4.3 AP4B1 Achchuthan Shanmugasundram reviewed gene: AP4B1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset hereditary spastic paraplegia v4.2 UCHL1 Achchuthan Shanmugasundram Source Expert Review Green was added to UCHL1.
Mode of inheritance for gene UCHL1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset hereditary spastic paraplegia v4.2 PRNP Achchuthan Shanmugasundram Source Expert Review Green was added to PRNP.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset hereditary spastic paraplegia v4.2 AP4S1 Achchuthan Shanmugasundram Source Expert Review Amber was added to AP4S1.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Adult onset hereditary spastic paraplegia v4.2 AP4M1 Achchuthan Shanmugasundram Source Expert Review Amber was added to AP4M1.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Adult onset hereditary spastic paraplegia v4.2 AP4E1 Achchuthan Shanmugasundram Source Expert Review Amber was added to AP4E1.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Adult onset hereditary spastic paraplegia v4.2 AP4B1 Achchuthan Shanmugasundram Source Expert Review Amber was added to AP4B1.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Adult onset dystonia, chorea or related movement disorder v3.19 GBA Achchuthan Shanmugasundram reviewed gene: GBA: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Adult onset dystonia, chorea or related movement disorder v3.19 GBA Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE was removed from gene: GBA.
Adult onset dystonia, chorea or related movement disorder v3.19 GBA Achchuthan Shanmugasundram Mode of inheritance for gene GBA was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v5.3 TNFRSF11A Achchuthan Shanmugasundram Tag for-review was removed from gene: TNFRSF11A.
Tag to_be_confirmed_NHSE was removed from gene: TNFRSF11A.
Skeletal dysplasia v5.3 TNFRSF11A Achchuthan Shanmugasundram changed review comment from: The mode of inheritance of this gene has been updated to'BOTH monoallelic and biallelic, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Skeletal dysplasia v5.3 ANAPC1 Achchuthan Shanmugasundram Tag for-review was removed from gene: ANAPC1.
Tag to_be_confirmed_NHSE was removed from gene: ANAPC1.
Skeletal dysplasia v5.3 ANAPC1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Skeletal dysplasia v5.3 UBA2 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Skeletal dysplasia v5.3 UBA2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: UBA2.
Tag Q4_23_NHS_review was removed from gene: UBA2.
Skeletal dysplasia v5.3 PSMC3 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: PSMC3.
Skeletal dysplasia v5.3 PSMC3 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance updated to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance updated to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.
Skeletal dysplasia v5.3 ERI1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance updated to 'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance updated to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Skeletal dysplasia v5.3 FBXW11 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: FBXW11.
Tag Q4_23_NHS_review was removed from gene: FBXW11.
Skeletal dysplasia v5.3 FBXW11 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance updated to 'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance updated to 'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown' following NHS Genomic Medicine Service approval.
Skeletal dysplasia v5.3 ERI1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ERI1.
Tag Q4_23_NHS_review was removed from gene: ERI1.
Skeletal dysplasia v5.3 AXIN1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: AXIN1.
Skeletal dysplasia v5.3 AXIN1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance updated to 'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance updated to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Skeletal dysplasia v5.3 SETD5 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: SETD5.
Tag Q3_23_NHS_review was removed from gene: SETD5.
Skeletal dysplasia v5.3 SETD5 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance updated to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance updated to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.
Skeletal dysplasia v5.3 UBA2 Achchuthan Shanmugasundram reviewed gene: UBA2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v5.3 TNFRSF11A Achchuthan Shanmugasundram reviewed gene: TNFRSF11A: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v5.3 SETD5 Achchuthan Shanmugasundram commented on gene: SETD5: The rating of this gene has been updated togreenand the mode of inheritance updated to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.
Skeletal dysplasia v5.3 PSMC3 Achchuthan Shanmugasundram commented on gene: PSMC3: The rating of this gene has been updated togreenand the mode of inheritance updated to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.
Skeletal dysplasia v5.3 FBXW11 Achchuthan Shanmugasundram reviewed gene: FBXW11: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Skeletal dysplasia v5.3 ERI1 Achchuthan Shanmugasundram commented on gene: ERI1: The rating of this gene has been updated togreenand the mode of inheritance updated to 'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.
Skeletal dysplasia v5.3 AXIN1 Achchuthan Shanmugasundram commented on gene: AXIN1: The rating of this gene has been updated togreenand the mode of inheritance updated to 'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.
Skeletal dysplasia v5.3 ANAPC1 Achchuthan Shanmugasundram reviewed gene: ANAPC1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v5.2 UBA2 Achchuthan Shanmugasundram Source NHS GMS was added to UBA2.
Source Expert Review Green was added to UBA2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v5.2 TNFRSF11A Achchuthan Shanmugasundram Mode of inheritance for gene TNFRSF11A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v5.2 SETD5 Achchuthan Shanmugasundram Source Expert Review Green was added to SETD5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v5.2 PSMC3 Achchuthan Shanmugasundram Source NHS GMS was added to PSMC3.
Source Expert Review Green was added to PSMC3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v5.2 FBXW11 Achchuthan Shanmugasundram Source NHS GMS was added to FBXW11.
Source Expert Review Green was added to FBXW11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v5.2 ERI1 Achchuthan Shanmugasundram Source Expert Review Green was added to ERI1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v5.2 AXIN1 Achchuthan Shanmugasundram Source NHS GMS was added to AXIN1.
Source Expert Review Green was added to AXIN1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v5.2 ANAPC1 Achchuthan Shanmugasundram Source NHS GMS was added to ANAPC1.
Source Expert Review Green was added to ANAPC1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal ciliopathies v4.3 KIAA0586 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Skeletal ciliopathies v4.3 KIAA0586 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: KIAA0586.
Skeletal ciliopathies v4.3 PMM2 Achchuthan Shanmugasundram Tag Q3_23_expert_review was removed from gene: PMM2.
Tag Q3_23_demote_red was removed from gene: PMM2.
Skeletal ciliopathies v4.3 PMM2 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated to redfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to red following NHS Genomic Medicine Service approval.
Skeletal ciliopathies v4.3 PMM2 Achchuthan Shanmugasundram reviewed gene: PMM2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal ciliopathies v4.3 KIAA0586 Achchuthan Shanmugasundram reviewed gene: KIAA0586: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal ciliopathies v4.2 PMM2 Achchuthan Shanmugasundram Source Expert Review Red was added to PMM2.
Source NHS GMS was added to PMM2.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Skeletal ciliopathies v4.2 KIAA0586 Achchuthan Shanmugasundram Source Expert Review Green was added to KIAA0586.
Source NHS GMS was added to KIAA0586.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Limb disorders v5.4 FBXW11 Achchuthan Shanmugasundram Tag Q4_21_NHS_review was removed from gene: FBXW11.
Tag Q4_23_promote_green was removed from gene: FBXW11.
Limb disorders v5.4 FBXW11 Eleanor Williams edited their review of gene: FBXW11: Added comment: The rating of this gene has been updated togreenand the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown'following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Limb disorders v5.3 FBXW11 Achchuthan Shanmugasundram Source NHS GMS was added to FBXW11.
Source Expert Review Green was added to FBXW11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v5.3 SLC6A20 Achchuthan Shanmugasundram Tag Q4_23_demote_red was removed from gene: SLC6A20.
Tag Q4_23_expert_review was removed from gene: SLC6A20.
Likely inborn error of metabolism v5.3 VPS33A Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: VPS33A.
Likely inborn error of metabolism v5.3 VPS16 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: VPS16.
Likely inborn error of metabolism v5.3 SEC23B Achchuthan Shanmugasundram Tag Q4_23_MOI was removed from gene: SEC23B.
Likely inborn error of metabolism v5.3 PTCD3 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: PTCD3.
Likely inborn error of metabolism v5.3 PIGM Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: PIGM.
Tag Q4_23_NHS_review was removed from gene: PIGM.
Likely inborn error of metabolism v5.3 NUS1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: NUS1.
Likely inborn error of metabolism v5.3 MRM2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: MRM2.
Likely inborn error of metabolism v5.3 LMF1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: LMF1.
Likely inborn error of metabolism v5.3 HSPA9 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: HSPA9.
Tag Q4_23_NHS_review was removed from gene: HSPA9.
Likely inborn error of metabolism v5.3 GRN Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: GRN.
Likely inborn error of metabolism v5.3 GPIHBP1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: GPIHBP1.
Likely inborn error of metabolism v5.3 EDEM3 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: EDEM3.
Likely inborn error of metabolism v5.3 CTSF Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CTSF.
Likely inborn error of metabolism v5.3 COX5A Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: COX5A.
Likely inborn error of metabolism v5.3 ATP5E Achchuthan Shanmugasundram Tag new-gene-name was removed from gene: ATP5E.
Tag Q4_23_promote_green was removed from gene: ATP5E.
Likely inborn error of metabolism v5.3 ACACA Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ACACA.
Tag Q4_23_NHS_review was removed from gene: ACACA.
Likely inborn error of metabolism v5.3 VPS33A Sarah Leigh commented on gene: VPS33A: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Likely inborn error of metabolism v5.3 VPS16 Sarah Leigh commented on gene: VPS16: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Likely inborn error of metabolism v5.3 SLC6A20 Sarah Leigh commented on gene: SLC6A20: The rating of this gene has been updated to red following NHS Genomic Medicine Service approval. Comment from GMS: 'Demotion of a green gene - disease association refuted in OMIM, as the single variant has been classified as common in gnomAD database.'
Likely inborn error of metabolism v5.3 SEC23B Sarah Leigh reviewed gene: SEC23B: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v5.3 PTCD3 Sarah Leigh edited their review of gene: PTCD3: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v5.3 PIGM Sarah Leigh edited their review of gene: PIGM: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v5.3 NUS1 Sarah Leigh reviewed gene: NUS1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Likely inborn error of metabolism v5.3 MRM2 Sarah Leigh edited their review of gene: MRM2: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v5.3 LMF1 Sarah Leigh commented on gene: LMF1: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Likely inborn error of metabolism v5.3 HSPA9 Sarah Leigh edited their review of gene: HSPA9: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v5.3 GRN Sarah Leigh edited their review of gene: GRN: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v5.3 GPIHBP1 Sarah Leigh commented on gene: GPIHBP1: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Likely inborn error of metabolism v5.3 EDEM3 Sarah Leigh commented on gene: EDEM3: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Likely inborn error of metabolism v5.3 CTSF Sarah Leigh edited their review of gene: CTSF: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v5.3 COX5A Sarah Leigh edited their review of gene: COX5A: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v5.3 ATP5E Sarah Leigh edited their review of gene: ATP5E: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v5.3 ACACA Sarah Leigh edited their review of gene: ACACA: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v5.2 VPS33A Achchuthan Shanmugasundram Source Expert Review Green was added to VPS33A.
Source NHS GMS was added to VPS33A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v5.2 VPS16 Achchuthan Shanmugasundram Source Expert Review Green was added to VPS16.
Source NHS GMS was added to VPS16.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v5.2 SLC6A20 Achchuthan Shanmugasundram Source Expert Review Red was added to SLC6A20.
Source NHS GMS was added to SLC6A20.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Likely inborn error of metabolism v5.2 SEC23B Achchuthan Shanmugasundram Mode of inheritance for gene SEC23B was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v5.2 PTCD3 Achchuthan Shanmugasundram Source Expert Review Green was added to PTCD3.
Source NHS GMS was added to PTCD3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v5.2 PIGM Achchuthan Shanmugasundram Source Expert Review Green was added to PIGM.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v5.2 NUS1 Achchuthan Shanmugasundram Source Expert Review Green was added to NUS1.
Source NHS GMS was added to NUS1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v5.2 MRM2 Achchuthan Shanmugasundram Source Expert Review Green was added to MRM2.
Source NHS GMS was added to MRM2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v5.2 LMF1 Achchuthan Shanmugasundram Source Expert Review Green was added to LMF1.
Source NHS GMS was added to LMF1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v5.2 HSPA9 Achchuthan Shanmugasundram Source Expert Review Green was added to HSPA9.
Source NHS GMS was added to HSPA9.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v5.2 GRN Achchuthan Shanmugasundram Source Expert Review Green was added to GRN.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v5.2 GPIHBP1 Achchuthan Shanmugasundram Source Expert Review Green was added to GPIHBP1.
Source NHS GMS was added to GPIHBP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v5.2 EDEM3 Achchuthan Shanmugasundram Source Expert Review Green was added to EDEM3.
Source NHS GMS was added to EDEM3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v5.2 CTSF Achchuthan Shanmugasundram Source Expert Review Green was added to CTSF.
Source NHS GMS was added to CTSF.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v5.2 COX5A Achchuthan Shanmugasundram Source Expert Review Green was added to COX5A.
Source NHS GMS was added to COX5A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v5.2 ATP5E Achchuthan Shanmugasundram Source Expert Review Green was added to ATP5E.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v5.2 ACACA Achchuthan Shanmugasundram Source Expert Review Green was added to ACACA.
Source NHS GMS was added to ACACA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Congenital disorders of glycosylation v5.3 SEC23B Achchuthan Shanmugasundram Tag Q4_23_MOI was removed from gene: SEC23B.
Congenital disorders of glycosylation v5.3 PIGM Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: PIGM.
Congenital disorders of glycosylation v5.3 SEC23B Sarah Leigh edited their review of gene: SEC23B: Added comment: The mode of inheritance of this gene has been updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital disorders of glycosylation v5.3 PIGM Sarah Leigh edited their review of gene: PIGM: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital disorders of glycosylation v5.2 SEC23B Achchuthan Shanmugasundram Source NHS GMS was added to SEC23B.
Mode of inheritance for gene SEC23B was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Congenital disorders of glycosylation v5.2 PIGM Achchuthan Shanmugasundram Source Expert Review Green was added to PIGM.
Source NHS GMS was added to PIGM.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 SPI1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SPI1.
Tag Q4_23_NHS_review was removed from gene: SPI1.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 TRAF3IP2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: TRAF3IP2.
Tag Q4_23_NHS_review was removed from gene: TRAF3IP2.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 TFRC Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: TFRC.
Tag Q4_23_NHS_review was removed from gene: TFRC.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 STAT6 Achchuthan Shanmugasundram Tag watchlist was removed from gene: STAT6.
Tag Q4_23_promote_green was removed from gene: STAT6.
Tag treatable tag was added to gene: STAT6.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 SEC61A1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SEC61A1.
Tag Q4_23_NHS_review was removed from gene: SEC61A1.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 SAMD9L Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SAMD9L.
Tag Q4_23_NHS_review was removed from gene: SAMD9L.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 RELA Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: RELA.
Tag Q4_23_NHS_review was removed from gene: RELA.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 REL Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: REL.
Tag Q4_23_NHS_review was removed from gene: REL.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 RANBP2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: RANBP2.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 PTPN2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: PTPN2.
Tag Q4_23_NHS_review was removed from gene: PTPN2.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 PSMB10 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: PSMB10.
Tag Q4_23_NHS_review was removed from gene: PSMB10.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 POLD1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: POLD1.
Tag Q4_23_NHS_review was removed from gene: POLD1.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 NLRP1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: NLRP1.
Tag Q4_23_NHS_review was removed from gene: NLRP1.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 NFAT5 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: NFAT5.
Tag Q4_23_NHS_review was removed from gene: NFAT5.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 MECOM Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: MECOM.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 MCTS1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: MCTS1.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 LYN Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: LYN.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 JAK1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: JAK1.
Tag Q4_23_NHS_review was removed from gene: JAK1.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 IRF4 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: IRF4.
Tag Q4_23_NHS_review was removed from gene: IRF4.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 IRF2BP2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: IRF2BP2.
Tag Q4_23_NHS_review was removed from gene: IRF2BP2.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 IL23R Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: IL23R.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 HYOU1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: HYOU1.
Tag Q4_23_NHS_review was removed from gene: HYOU1.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 HMOX1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: HMOX1.
Tag Q4_23_NHS_review was removed from gene: HMOX1.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 DUT Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: DUT.
Tag Q4_23_NHS_review was removed from gene: DUT.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 CXCR2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CXCR2.
Tag Q4_23_NHS_review was removed from gene: CXCR2.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 CR2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CR2.
Tag Q4_23_NHS_review was removed from gene: CR2.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 CD81 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CD81.
Tag Q4_23_NHS_review was removed from gene: CD81.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 CD4 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CD4.
Tag Q4_23_NHS_review was removed from gene: CD4.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 CBLB Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CBLB.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 AICDA Achchuthan Shanmugasundram Tag Q4_23_MOI was removed from gene: AICDA.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 OTULIN Achchuthan Shanmugasundram Tag Q3_23_MOI was removed from gene: OTULIN.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 DOCK11 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: DOCK11.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 DIAPH1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: DIAPH1.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 ARPC5 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: ARPC5.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 DCLRE1B Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE was removed from gene: DCLRE1B.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 STAT5B Achchuthan Shanmugasundram Tag for-review was removed from gene: STAT5B.
Tag to_be_confirmed_NHSE was removed from gene: STAT5B.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 TRAF3IP2 Sarah Leigh reviewed gene: TRAF3IP2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 TFRC Sarah Leigh reviewed gene: TFRC: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 STAT6 Sarah Leigh reviewed gene: STAT6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 STAT5B Sarah Leigh reviewed gene: STAT5B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 SPI1 Sarah Leigh reviewed gene: SPI1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 SEC61A1 Sarah Leigh reviewed gene: SEC61A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 SAMD9L Sarah Leigh reviewed gene: SAMD9L: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 RELA Sarah Leigh reviewed gene: RELA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 REL Sarah Leigh reviewed gene: REL: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 RANBP2 Sarah Leigh reviewed gene: RANBP2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 PTPN2 Sarah Leigh reviewed gene: PTPN2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 PSMB10 Sarah Leigh edited their review of gene: PSMB10: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 POLD1 Sarah Leigh reviewed gene: POLD1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 OTULIN Sarah Leigh edited their review of gene: OTULIN: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 NLRP1 Sarah Leigh reviewed gene: NLRP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 NFAT5 Sarah Leigh edited their review of gene: NFAT5: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 MECOM Sarah Leigh reviewed gene: MECOM: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 MCTS1 Sarah Leigh reviewed gene: MCTS1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 LYN Sarah Leigh reviewed gene: LYN: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 JAK1 Sarah Leigh reviewed gene: JAK1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 IRF4 Sarah Leigh reviewed gene: IRF4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 IRF2BP2 Sarah Leigh reviewed gene: IRF2BP2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 IL23R Sarah Leigh reviewed gene: IL23R: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 HYOU1 Sarah Leigh reviewed gene: HYOU1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 HMOX1 Sarah Leigh reviewed gene: HMOX1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 DUT Sarah Leigh reviewed gene: DUT: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 DOCK11 Sarah Leigh reviewed gene: DOCK11: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 DIAPH1 Sarah Leigh reviewed gene: DIAPH1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 DCLRE1B Sarah Leigh reviewed gene: DCLRE1B: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 CXCR2 Sarah Leigh reviewed gene: CXCR2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 CR2 Sarah Leigh edited their review of gene: CR2: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 CD81 Sarah Leigh reviewed gene: CD81: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 CD4 Sarah Leigh reviewed gene: CD4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 CBLB Sarah Leigh reviewed gene: CBLB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 ARPC5 Sarah Leigh reviewed gene: ARPC5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 AICDA Sarah Leigh reviewed gene: AICDA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 TRAF3IP2 Achchuthan Shanmugasundram Source NHS GMS was added to TRAF3IP2.
Source Expert Review Green was added to TRAF3IP2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 TFRC Achchuthan Shanmugasundram Source NHS GMS was added to TFRC.
Source Expert Review Green was added to TFRC.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 STAT6 Achchuthan Shanmugasundram Source NHS GMS was added to STAT6.
Source Expert Review Green was added to STAT6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 STAT5B Achchuthan Shanmugasundram Mode of inheritance for gene STAT5B was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 SPI1 Achchuthan Shanmugasundram Source NHS GMS was added to SPI1.
Source Expert Review Green was added to SPI1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 SEC61A1 Achchuthan Shanmugasundram Source NHS GMS was added to SEC61A1.
Source Expert Review Green was added to SEC61A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 SAMD9L Achchuthan Shanmugasundram Source Expert Review Green was added to SAMD9L.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 RELA Achchuthan Shanmugasundram Source NHS GMS was added to RELA.
Source Expert Review Green was added to RELA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 REL Achchuthan Shanmugasundram Source NHS GMS was added to REL.
Source Expert Review Green was added to REL.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 RANBP2 Achchuthan Shanmugasundram Source Expert Review Green was added to RANBP2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 PTPN2 Achchuthan Shanmugasundram Source NHS GMS was added to PTPN2.
Source Expert Review Green was added to PTPN2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 PSMB10 Achchuthan Shanmugasundram Source NHS GMS was added to PSMB10.
Source Expert Review Green was added to PSMB10.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 POLD1 Achchuthan Shanmugasundram Source NHS GMS was added to POLD1.
Source Expert Review Green was added to POLD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 OTULIN Achchuthan Shanmugasundram Mode of inheritance for gene OTULIN was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 NLRP1 Achchuthan Shanmugasundram Source Expert Review Green was added to NLRP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 NFAT5 Achchuthan Shanmugasundram Source NHS GMS was added to NFAT5.
Source Expert Review Green was added to NFAT5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 MECOM Achchuthan Shanmugasundram Source NHS GMS was added to MECOM.
Source Expert Review Green was added to MECOM.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 MCTS1 Achchuthan Shanmugasundram Source NHS GMS was added to MCTS1.
Source Expert Review Green was added to MCTS1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 LYN Achchuthan Shanmugasundram Source NHS GMS was added to LYN.
Source Expert Review Green was added to LYN.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 JAK1 Achchuthan Shanmugasundram Source NHS GMS was added to JAK1.
Source Expert Review Green was added to JAK1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 IRF4 Achchuthan Shanmugasundram Source NHS GMS was added to IRF4.
Source Expert Review Green was added to IRF4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 IRF2BP2 Achchuthan Shanmugasundram Source NHS GMS was added to IRF2BP2.
Source Expert Review Green was added to IRF2BP2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 IL23R Achchuthan Shanmugasundram Source NHS GMS was added to IL23R.
Source Expert Review Green was added to IL23R.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 HYOU1 Achchuthan Shanmugasundram Source NHS GMS was added to HYOU1.
Source Expert Review Green was added to HYOU1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 HMOX1 Achchuthan Shanmugasundram Source NHS GMS was added to HMOX1.
Source Expert Review Green was added to HMOX1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 DUT Achchuthan Shanmugasundram Source NHS GMS was added to DUT.
Source Expert Review Green was added to DUT.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 DOCK11 Achchuthan Shanmugasundram Source NHS GMS was added to DOCK11.
Source Expert Review Green was added to DOCK11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 DIAPH1 Achchuthan Shanmugasundram Source NHS GMS was added to DIAPH1.
Source Expert Review Green was added to DIAPH1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 DCLRE1B Achchuthan Shanmugasundram Source Expert Review Amber was added to DCLRE1B.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 CXCR2 Achchuthan Shanmugasundram Source NHS GMS was added to CXCR2.
Source Expert Review Green was added to CXCR2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 CR2 Achchuthan Shanmugasundram Source NHS GMS was added to CR2.
Source Expert Review Green was added to CR2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 CD81 Achchuthan Shanmugasundram Source NHS GMS was added to CD81.
Source Expert Review Green was added to CD81.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 CD4 Achchuthan Shanmugasundram Source NHS GMS was added to CD4.
Source Expert Review Green was added to CD4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 CBLB Achchuthan Shanmugasundram Source NHS GMS was added to CBLB.
Source Expert Review Green was added to CBLB.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 ARPC5 Achchuthan Shanmugasundram Source NHS GMS was added to ARPC5.
Source Expert Review Green was added to ARPC5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 AICDA Achchuthan Shanmugasundram Mode of inheritance for gene AICDA was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sickle cell, thalassaemia and other haemoglobinopathies v1.9 HBG2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: HBG2.
Sickle cell, thalassaemia and other haemoglobinopathies v1.9 HBG1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: HBG1.
Sickle cell, thalassaemia and other haemoglobinopathies v1.9 HBA2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: HBA2.
Sickle cell, thalassaemia and other haemoglobinopathies v1.9 HBG2 Sarah Leigh reviewed gene: HBG2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sickle cell, thalassaemia and other haemoglobinopathies v1.9 HBG1 Sarah Leigh reviewed gene: HBG1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sickle cell, thalassaemia and other haemoglobinopathies v1.9 HBA2 Sarah Leigh reviewed gene: HBA2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Sickle cell, thalassaemia and other haemoglobinopathies v1.8 HBG2 Achchuthan Shanmugasundram Source Expert Review Green was added to HBG2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Sickle cell, thalassaemia and other haemoglobinopathies v1.8 HBG1 Achchuthan Shanmugasundram Source Expert Review Green was added to HBG1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Sickle cell, thalassaemia and other haemoglobinopathies v1.8 HBA2 Achchuthan Shanmugasundram Source Expert Review Green was added to HBA2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Sickle cell, thalassaemia and other haemoglobinopathies trait or carrier testing v1.9 HBG2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: HBG2.
Sickle cell, thalassaemia and other haemoglobinopathies trait or carrier testing v1.9 HBG1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: HBG1.
Sickle cell, thalassaemia and other haemoglobinopathies trait or carrier testing v1.9 HBA2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: HBA2.
Sickle cell, thalassaemia and other haemoglobinopathies trait or carrier testing v1.9 HBG2 Sarah Leigh reviewed gene: HBG2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sickle cell, thalassaemia and other haemoglobinopathies trait or carrier testing v1.9 HBG1 Sarah Leigh reviewed gene: HBG1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sickle cell, thalassaemia and other haemoglobinopathies trait or carrier testing v1.9 HBA2 Sarah Leigh reviewed gene: HBA2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Sickle cell, thalassaemia and other haemoglobinopathies trait or carrier testing v1.8 HBG2 Achchuthan Shanmugasundram Source Expert Review Green was added to HBG2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Sickle cell, thalassaemia and other haemoglobinopathies trait or carrier testing v1.8 HBG1 Achchuthan Shanmugasundram Source Expert Review Green was added to HBG1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Sickle cell, thalassaemia and other haemoglobinopathies trait or carrier testing v1.8 HBA2 Achchuthan Shanmugasundram Source Expert Review Green was added to HBA2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Neonatal diabetes v4.6 ONECUT1 Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE was removed from gene: ONECUT1.
Neonatal diabetes v4.6 CNOT1 Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE was removed from gene: CNOT1.
Neonatal diabetes v4.6 ONECUT1 Sarah Leigh reviewed gene: ONECUT1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Neonatal diabetes v4.6 CNOT1 Sarah Leigh reviewed gene: CNOT1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Neonatal diabetes v4.5 ONECUT1 Achchuthan Shanmugasundram Source NHS GMS was added to ONECUT1.
Source Expert Review Green was added to ONECUT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Neonatal diabetes v4.5 CNOT1 Achchuthan Shanmugasundram Source NHS GMS was added to CNOT1.
Source Expert Review Green was added to CNOT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Lipodystrophy - childhood onset v4.52 AKT2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: AKT2.
Tag Q3_23_NHS_review was removed from gene: AKT2.
Lipodystrophy - childhood onset v4.52 WRN Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toGreenand the mode of inheritance set toBIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Lipodystrophy - childhood onset v4.52 WRN Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: WRN.
Tag Q3_23_NHS_review was removed from gene: WRN.
Lipodystrophy - childhood onset v4.52 PSMB8 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PSMB8.
Tag Q3_23_NHS_review was removed from gene: PSMB8.
Lipodystrophy - childhood onset v4.52 PSMB8 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toGreenand the mode of inheritance set toBIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Lipodystrophy - childhood onset v4.52 PSMB4 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toGreenand the mode of inheritance set toBIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Lipodystrophy - childhood onset v4.52 PSMB4 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PSMB4.
Tag Q3_23_NHS_review was removed from gene: PSMB4.
Lipodystrophy - childhood onset v4.52 POC1A Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: POC1A.
Tag Q3_23_NHS_review was removed from gene: POC1A.
Lipodystrophy - childhood onset v4.52 POC1A Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toGreenand the mode of inheritance set toBIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Lipodystrophy - childhood onset v4.52 PIK3R1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toGreenand the mode of inheritance set toMONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Lipodystrophy - childhood onset v4.52 PIK3R1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PIK3R1.
Tag Q3_23_NHS_review was removed from gene: PIK3R1.
Lipodystrophy - childhood onset v4.52 PCYT1A Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toGreenand the mode of inheritance set toBIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Lipodystrophy - childhood onset v4.52 PCYT1A Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PCYT1A.
Tag Q3_23_NHS_review was removed from gene: PCYT1A.
Lipodystrophy - childhood onset v4.52 PCNT Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PCNT.
Tag Q3_23_NHS_review was removed from gene: PCNT.
Lipodystrophy - childhood onset v4.52 PCNT Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toGreenand the mode of inheritance set toBIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Lipodystrophy - childhood onset v4.52 MFN2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: MFN2.
Tag Q3_23_NHS_review was removed from gene: MFN2.
Lipodystrophy - childhood onset v4.52 MFN2 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toGreenand the mode of inheritance set toBIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Lipodystrophy - childhood onset v4.52 EPHX1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toGreenand the mode of inheritance set toMONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Lipodystrophy - childhood onset v4.52 EPHX1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: EPHX1.
Tag Q3_23_NHS_review was removed from gene: EPHX1.
Lipodystrophy - childhood onset v4.52 BLM Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: BLM.
Tag Q3_23_NHS_review was removed from gene: BLM.
Lipodystrophy - childhood onset v4.52 BLM Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toGreenand the mode of inheritance set toBIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Lipodystrophy - childhood onset v4.52 ALMS1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: ALMS1.
Tag Q3_23_NHS_review was removed from gene: ALMS1.
Lipodystrophy - childhood onset v4.52 ALMS1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toGreenand the mode of inheritance set toBIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Lipodystrophy - childhood onset v4.52 WRN Achchuthan Shanmugasundram commented on gene: WRN: The rating of this gene has been updated toGreenand the mode of inheritance set toBIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Lipodystrophy - childhood onset v4.52 PSMB8 Achchuthan Shanmugasundram commented on gene: PSMB8: The rating of this gene has been updated toGreenand the mode of inheritance set toBIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Lipodystrophy - childhood onset v4.52 PSMB4 Achchuthan Shanmugasundram commented on gene: PSMB4: The rating of this gene has been updated toGreenand the mode of inheritance set toBIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Lipodystrophy - childhood onset v4.52 POC1A Achchuthan Shanmugasundram commented on gene: POC1A: The rating of this gene has been updated toGreenand the mode of inheritance set toBIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Lipodystrophy - childhood onset v4.52 PIK3R1 Achchuthan Shanmugasundram commented on gene: PIK3R1: The rating of this gene has been updated toGreenand the mode of inheritance set toMONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Lipodystrophy - childhood onset v4.52 PCYT1A Achchuthan Shanmugasundram commented on gene: PCYT1A: The rating of this gene has been updated toGreenand the mode of inheritance set toBIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Lipodystrophy - childhood onset v4.52 PCNT Achchuthan Shanmugasundram commented on gene: PCNT: The rating of this gene has been updated toGreenand the mode of inheritance set toBIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Lipodystrophy - childhood onset v4.52 MFN2 Achchuthan Shanmugasundram commented on gene: MFN2: The rating of this gene has been updated toGreenand the mode of inheritance set toBIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Lipodystrophy - childhood onset v4.52 EPHX1 Achchuthan Shanmugasundram commented on gene: EPHX1: The rating of this gene has been updated toGreenand the mode of inheritance set toMONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Lipodystrophy - childhood onset v4.52 BLM Achchuthan Shanmugasundram commented on gene: BLM: The rating of this gene has been updated toGreenand the mode of inheritance set toBIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Lipodystrophy - childhood onset v4.52 ALMS1 Achchuthan Shanmugasundram commented on gene: ALMS1: The rating of this gene has been updated toGreenand the mode of inheritance set toBIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Lipodystrophy - childhood onset v4.52 AKT2 Achchuthan Shanmugasundram edited their review of gene: AKT2: Added comment: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber. Comment from GMS: 'Should be amber. Another family is needed for AKT2 for this to be upgraded to Green. The two variants used as evidence, p.Arg467Trp and p.Arg208Lys, far too common in gnomAD to be causing a rare AD disorder.'; Changed rating: AMBER
Lipodystrophy - childhood onset v4.51 WRN Achchuthan Shanmugasundram Source Expert Review Green was added to WRN.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Lipodystrophy - childhood onset v4.51 PSMB8 Achchuthan Shanmugasundram Source Expert Review Green was added to PSMB8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Lipodystrophy - childhood onset v4.51 PSMB4 Achchuthan Shanmugasundram Source Expert Review Green was added to PSMB4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Lipodystrophy - childhood onset v4.51 POC1A Achchuthan Shanmugasundram Source Expert Review Green was added to POC1A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Lipodystrophy - childhood onset v4.51 PIK3R1 Achchuthan Shanmugasundram Source Expert Review Green was added to PIK3R1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Lipodystrophy - childhood onset v4.51 PCYT1A Achchuthan Shanmugasundram Source Expert Review Green was added to PCYT1A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Lipodystrophy - childhood onset v4.51 PCNT Achchuthan Shanmugasundram Source Expert Review Green was added to PCNT.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Lipodystrophy - childhood onset v4.51 MFN2 Achchuthan Shanmugasundram Source Expert Review Green was added to MFN2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Lipodystrophy - childhood onset v4.51 EPHX1 Achchuthan Shanmugasundram Source Expert Review Green was added to EPHX1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Lipodystrophy - childhood onset v4.51 BLM Achchuthan Shanmugasundram Source Expert Review Green was added to BLM.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Lipodystrophy - childhood onset v4.51 ALMS1 Achchuthan Shanmugasundram Source Expert Review Green was added to ALMS1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v4.3 NOTCH3 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: NOTCH3.
Tag Q4_23_expert_review was removed from gene: NOTCH3.
Paediatric disorders - additional genes v4.3 TAB2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: TAB2.
Paediatric disorders - additional genes v4.3 TAB2 Sarah Leigh edited their review of gene: TAB2: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric disorders - additional genes v4.3 NOTCH3 Sarah Leigh reviewed gene: NOTCH3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Paediatric disorders - additional genes v4.2 TAB2 Achchuthan Shanmugasundram Source Expert Review Green was added to TAB2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v4.2 NOTCH3 Achchuthan Shanmugasundram Source Expert Review Green was added to NOTCH3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.11 FAM111A Achchuthan Shanmugasundram Tag Q4_23_demote_red was removed from gene: FAM111A.
Tag Q4_23_NHS_review was removed from gene: FAM111A.
Tag Q4_23_expert_review was removed from gene: FAM111A.
Intellectual disability v6.11 DPP6 Achchuthan Shanmugasundram Tag Q4_23_demote_red was removed from gene: DPP6.
Tag Q4_23_NHS_review was removed from gene: DPP6.
Tag Q4_23_expert_review was removed from gene: DPP6.
Intellectual disability v6.11 ZBTB47 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ZBTB47.
Intellectual disability v6.11 VCP Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: VCP.
Intellectual disability v6.11 TEFM Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: TEFM.
Intellectual disability v6.11 SRSF1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SRSF1.
Intellectual disability v6.11 SHQ1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SHQ1.
Intellectual disability v6.11 RPL10 Achchuthan Shanmugasundram Tag Q4_23_MOI was removed from gene: RPL10.
Intellectual disability v6.11 RELN Achchuthan Shanmugasundram Tag Q4_23_MOI was removed from gene: RELN.
Intellectual disability v6.11 RBL2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: RBL2.
Tag Q4_23_NHS_review was removed from gene: RBL2.
Intellectual disability v6.11 RAP1B Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: RAP1B.
Intellectual disability v6.11 MYH10 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: MYH10.
Intellectual disability v6.11 MAST4 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: MAST4.
Intellectual disability v6.11 KMT2B Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: KMT2B.
Intellectual disability v6.11 ERI1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ERI1.
Intellectual disability v6.11 COX11 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: COX11.
Intellectual disability v6.11 CLDN11 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CLDN11.
Intellectual disability v6.11 CLCN6 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CLCN6.
Intellectual disability v6.11 CDK16 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CDK16.
Tag Q4_23_NHS_review was removed from gene: CDK16.
Intellectual disability v6.11 CASP2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CASP2.
Intellectual disability v6.11 ARF3 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ARF3.
Intellectual disability v6.11 ACACA Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ACACA.
Intellectual disability v6.11 FAR1 Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE was removed from gene: FAR1.
Intellectual disability v6.11 U2AF2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: U2AF2.
Tag Q3_23_NHS_review was removed from gene: U2AF2.
Intellectual disability v6.11 TTI1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: TTI1.
Intellectual disability v6.11 TSPOAP1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: TSPOAP1.
Intellectual disability v6.11 TMEM63B Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: TMEM63B.
Intellectual disability v6.11 SLC30A9 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: SLC30A9.
Intellectual disability v6.11 RPS6KA3 Achchuthan Shanmugasundram Tag Q3_23_MOI was removed from gene: RPS6KA3.
Intellectual disability v6.11 RAB5C Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: RAB5C.
Intellectual disability v6.11 PSMC3 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PSMC3.
Intellectual disability v6.11 PPP1R3F Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PPP1R3F.
Intellectual disability v6.11 PIP5K1C Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PIP5K1C.
Intellectual disability v6.11 PABPC1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PABPC1.
Tag Q3_23_MOI was removed from gene: PABPC1.
Tag Q3_23_phenotype was removed from gene: PABPC1.
Intellectual disability v6.11 NR2F2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: NR2F2.
Tag Q3_23_NHS_review was removed from gene: NR2F2.
Intellectual disability v6.11 NEUROG1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: NEUROG1.
Tag Q3_23_NHS_review was removed from gene: NEUROG1.
Intellectual disability v6.11 LETM1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: LETM1.
Tag Q3_23_MOI was removed from gene: LETM1.
Intellectual disability v6.11 KCNH5 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: KCNH5.
Intellectual disability v6.11 ESAM Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: ESAM.
Tag Q3_23_NHS_review was removed from gene: ESAM.
Intellectual disability v6.11 EIF4A2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: EIF4A2.
Intellectual disability v6.11 DHX9 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: DHX9.
Intellectual disability v6.11 DAGLA Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: DAGLA.
Intellectual disability v6.11 CNOT9 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: CNOT9.
Intellectual disability v6.11 ATP6V0C Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: ATP6V0C.
Tag Q3_23_NHS_review was removed from gene: ATP6V0C.
Intellectual disability v6.11 AGTPBP1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: AGTPBP1.
Intellectual disability v6.11 ZBTB47 Sarah Leigh edited their review of gene: ZBTB47: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 VCP Sarah Leigh reviewed gene: VCP: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 U2AF2 Sarah Leigh reviewed gene: U2AF2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 TTI1 Sarah Leigh commented on gene: TTI1: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Intellectual disability v6.11 TSPOAP1 Sarah Leigh edited their review of gene: TSPOAP1: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v6.11 TMEM63B Sarah Leigh reviewed gene: TMEM63B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 TEFM Sarah Leigh reviewed gene: TEFM: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v6.11 SRSF1 Sarah Leigh reviewed gene: SRSF1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 SLC30A9 Sarah Leigh edited their review of gene: SLC30A9: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v6.11 SHQ1 Sarah Leigh edited their review of gene: SHQ1: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v6.11 RPS6KA3 Sarah Leigh reviewed gene: RPS6KA3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v6.11 RPL10 Sarah Leigh commented on gene: RPL10: The mode of inheritance of this gene has been updated to X-LINKED: hemizygous mutation in males, biallelic mutations in females following NHS Genomic Medicine Service approval.
Intellectual disability v6.11 RELN Sarah Leigh reviewed gene: RELN: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v6.11 RBL2 Sarah Leigh commented on gene: RBL2: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Intellectual disability v6.11 RAP1B Sarah Leigh reviewed gene: RAP1B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 RAB5C Sarah Leigh reviewed gene: RAB5C: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 PSMC3 Sarah Leigh reviewed gene: PSMC3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 PPP1R3F Sarah Leigh reviewed gene: PPP1R3F: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v6.11 PIP5K1C Sarah Leigh reviewed gene: PIP5K1C: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 PABPC1 Sarah Leigh edited their review of gene: PABPC1: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v6.11 NR2F2 Sarah Leigh reviewed gene: NR2F2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 NEUROG1 Sarah Leigh reviewed gene: NEUROG1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v6.11 MYH10 Sarah Leigh reviewed gene: MYH10: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 MAST4 Sarah Leigh edited their review of gene: MAST4: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 LETM1 Sarah Leigh commented on gene: LETM1: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Intellectual disability v6.11 KMT2B Sarah Leigh reviewed gene: KMT2B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v6.11 KCNH5 Sarah Leigh reviewed gene: KCNH5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 FAR1 Sarah Leigh commented on gene: FAR1: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Intellectual disability v6.11 FAM111A Sarah Leigh commented on gene: FAM111A: The rating of this gene has been updated to red following NHS Genomic Medicine Service approval.
Intellectual disability v6.11 ESAM Sarah Leigh reviewed gene: ESAM: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v6.11 ERI1 Sarah Leigh reviewed gene: ERI1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v6.11 EIF4A2 Sarah Leigh commented on gene: EIF4A2: The rating of this gene has been updated to Green and the mode of inheritance set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval
Intellectual disability v6.11 DPP6 Sarah Leigh reviewed gene: DPP6: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v6.11 DHX9 Sarah Leigh reviewed gene: DHX9: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 DAGLA Sarah Leigh reviewed gene: DAGLA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 COX11 Sarah Leigh edited their review of gene: COX11: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v6.11 CNOT9 Sarah Leigh reviewed gene: CNOT9: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 CLDN11 Sarah Leigh reviewed gene: CLDN11: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 CLCN6 Sarah Leigh commented on gene: CLCN6: The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.
Intellectual disability v6.11 CDK16 Sarah Leigh commented on gene: CDK16: The rating of this gene has been updated to green and the mode of inheritance updated to X-LINKED: hemizygous mutation in males, biallelic mutations in females following NHS Genomic Medicine Service approval.
Intellectual disability v6.11 CASP2 Sarah Leigh edited their review of gene: CASP2: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v6.11 ATP6V0C Sarah Leigh reviewed gene: ATP6V0C: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 ARF3 Sarah Leigh reviewed gene: ARF3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v6.11 AGTPBP1 Sarah Leigh reviewed gene: AGTPBP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v6.11 ACACA Sarah Leigh edited their review of gene: ACACA: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v6.10 ZBTB47 Achchuthan Shanmugasundram Source Expert Review Green was added to ZBTB47.
Source NHS GMS was added to ZBTB47.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 VCP Achchuthan Shanmugasundram Source Expert Review Green was added to VCP.
Source NHS GMS was added to VCP.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 U2AF2 Achchuthan Shanmugasundram Source Expert Review Green was added to U2AF2.
Source NHS GMS was added to U2AF2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 TTI1 Achchuthan Shanmugasundram Source Expert Review Green was added to TTI1.
Source NHS GMS was added to TTI1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 TSPOAP1 Achchuthan Shanmugasundram Source Expert Review Green was added to TSPOAP1.
Source NHS GMS was added to TSPOAP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 TMEM63B Achchuthan Shanmugasundram Source Expert Review Green was added to TMEM63B.
Source NHS GMS was added to TMEM63B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 TEFM Achchuthan Shanmugasundram Source Expert Review Green was added to TEFM.
Source NHS GMS was added to TEFM.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 SRSF1 Achchuthan Shanmugasundram Source Expert Review Green was added to SRSF1.
Source NHS GMS was added to SRSF1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 SLC30A9 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC30A9.
Source NHS GMS was added to SLC30A9.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 SHQ1 Achchuthan Shanmugasundram Source Expert Review Green was added to SHQ1.
Source NHS GMS was added to SHQ1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 RPS6KA3 Achchuthan Shanmugasundram Source NHS GMS was added to RPS6KA3.
Mode of inheritance for gene RPS6KA3 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)
Intellectual disability v6.10 RPL10 Achchuthan Shanmugasundram Source NHS GMS was added to RPL10.
Mode of inheritance for gene RPL10 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v6.10 RELN Achchuthan Shanmugasundram Source NHS GMS was added to RELN.
Mode of inheritance for gene RELN was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v6.10 RBL2 Achchuthan Shanmugasundram Source Expert Review Green was added to RBL2.
Source NHS GMS was added to RBL2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 RAP1B Achchuthan Shanmugasundram Source Expert Review Green was added to RAP1B.
Source NHS GMS was added to RAP1B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 RAB5C Achchuthan Shanmugasundram Source Expert Review Green was added to RAB5C.
Source NHS GMS was added to RAB5C.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 PSMC3 Achchuthan Shanmugasundram Source Expert Review Green was added to PSMC3.
Source NHS GMS was added to PSMC3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 PPP1R3F Achchuthan Shanmugasundram Source Expert Review Green was added to PPP1R3F.
Source NHS GMS was added to PPP1R3F.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 PIP5K1C Achchuthan Shanmugasundram Source Expert Review Green was added to PIP5K1C.
Source NHS GMS was added to PIP5K1C.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 PABPC1 Achchuthan Shanmugasundram Source Expert Review Green was added to PABPC1.
Source NHS GMS was added to PABPC1.
Mode of inheritance for gene PABPC1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 NR2F2 Achchuthan Shanmugasundram Source Expert Review Green was added to NR2F2.
Source NHS GMS was added to NR2F2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 NEUROG1 Achchuthan Shanmugasundram Source Expert Review Green was added to NEUROG1.
Source NHS GMS was added to NEUROG1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 MYH10 Achchuthan Shanmugasundram Source Expert Review Green was added to MYH10.
Source NHS GMS was added to MYH10.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 MAST4 Achchuthan Shanmugasundram Source Expert Review Green was added to MAST4.
Source NHS GMS was added to MAST4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 LETM1 Achchuthan Shanmugasundram Source Expert Review Green was added to LETM1.
Source NHS GMS was added to LETM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 KMT2B Achchuthan Shanmugasundram Source Expert Review Green was added to KMT2B.
Source NHS GMS was added to KMT2B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 KCNH5 Achchuthan Shanmugasundram Source Expert Review Green was added to KCNH5.
Source NHS GMS was added to KCNH5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 FAR1 Achchuthan Shanmugasundram Source NHS GMS was added to FAR1.
Mode of inheritance for gene FAR1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Intellectual disability v6.10 FAM111A Achchuthan Shanmugasundram Source Expert Review Red was added to FAM111A.
Source NHS GMS was added to FAM111A.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Intellectual disability v6.10 ESAM Achchuthan Shanmugasundram Source Expert Review Green was added to ESAM.
Source NHS GMS was added to ESAM.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 ERI1 Achchuthan Shanmugasundram Source Expert Review Green was added to ERI1.
Source NHS GMS was added to ERI1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 EIF4A2 Achchuthan Shanmugasundram Source Expert Review Green was added to EIF4A2.
Source NHS GMS was added to EIF4A2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 DPP6 Achchuthan Shanmugasundram Source Expert Review Red was added to DPP6.
Source NHS GMS was added to DPP6.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Intellectual disability v6.10 DHX9 Achchuthan Shanmugasundram Source Expert Review Green was added to DHX9.
Source NHS GMS was added to DHX9.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 DAGLA Achchuthan Shanmugasundram Source Expert Review Green was added to DAGLA.
Source NHS GMS was added to DAGLA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 COX11 Achchuthan Shanmugasundram Source Expert Review Green was added to COX11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 CNOT9 Achchuthan Shanmugasundram Source Expert Review Green was added to CNOT9.
Source NHS GMS was added to CNOT9.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 CLDN11 Achchuthan Shanmugasundram Source Expert Review Green was added to CLDN11.
Source NHS GMS was added to CLDN11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 CLCN6 Achchuthan Shanmugasundram Source Expert Review Green was added to CLCN6.
Source NHS GMS was added to CLCN6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 CDK16 Achchuthan Shanmugasundram Source Expert Review Green was added to CDK16.
Source NHS GMS was added to CDK16.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 CASP2 Achchuthan Shanmugasundram Source Expert Review Green was added to CASP2.
Source NHS GMS was added to CASP2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 ATP6V0C Achchuthan Shanmugasundram Source Expert Review Green was added to ATP6V0C.
Source NHS GMS was added to ATP6V0C.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 ARF3 Achchuthan Shanmugasundram Source Expert Review Green was added to ARF3.
Source NHS GMS was added to ARF3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 AGTPBP1 Achchuthan Shanmugasundram Source Expert Review Green was added to AGTPBP1.
Source NHS GMS was added to AGTPBP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 ACACA Achchuthan Shanmugasundram Source Expert Review Green was added to ACACA.
Source NHS GMS was added to ACACA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Inherited polyposis and early onset colorectal cancer - germline testing v2.11 GREM1 Achchuthan Shanmugasundram reviewed gene: GREM1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Inherited polyposis and early onset colorectal cancer - germline testing v2.11 GREM1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: GREM1.
Tag Q4_23_NHS_review was removed from gene: GREM1.
Inherited polyposis and early onset colorectal cancer - germline testing v2.11 GREM1 Achchuthan Shanmugasundram Source Expert Review Green was added to GREM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric or syndromic cardiomyopathy v4.3 SLC22A5 Achchuthan Shanmugasundram Tag Q4_23_MOI was removed from gene: SLC22A5.
Paediatric or syndromic cardiomyopathy v4.3 TAB2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: TAB2.
Paediatric or syndromic cardiomyopathy v4.3 LETM1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: LETM1.
Tag Q3_23_MOI was removed from gene: LETM1.
Paediatric or syndromic cardiomyopathy v4.3 LDB3 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: LDB3.
Paediatric or syndromic cardiomyopathy v4.3 ELAC2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: ELAC2.
Tag Q3_23_NHS_review was removed from gene: ELAC2.
Paediatric or syndromic cardiomyopathy v4.3 CAP2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: CAP2.
Paediatric or syndromic cardiomyopathy v4.3 TAB2 Sarah Leigh edited their review of gene: TAB2: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric or syndromic cardiomyopathy v4.3 SLC22A5 Sarah Leigh commented on gene: SLC22A5: The mode of inheritance of this gene has been updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Paediatric or syndromic cardiomyopathy v4.3 LETM1 Sarah Leigh commented on gene: LETM1: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Paediatric or syndromic cardiomyopathy v4.3 LDB3 Sarah Leigh reviewed gene: LDB3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric or syndromic cardiomyopathy v4.3 ELAC2 Sarah Leigh reviewed gene: ELAC2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric or syndromic cardiomyopathy v4.3 CAP2 Sarah Leigh reviewed gene: CAP2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric or syndromic cardiomyopathy v4.2 TAB2 Achchuthan Shanmugasundram Source Expert Review Green was added to TAB2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric or syndromic cardiomyopathy v4.2 SLC22A5 Achchuthan Shanmugasundram Mode of inheritance for gene SLC22A5 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Paediatric or syndromic cardiomyopathy v4.2 LETM1 Achchuthan Shanmugasundram Source NHS GMS was added to LETM1.
Source Expert Review Green was added to LETM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric or syndromic cardiomyopathy v4.2 LDB3 Achchuthan Shanmugasundram Source Expert Review Green was added to LDB3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric or syndromic cardiomyopathy v4.2 ELAC2 Achchuthan Shanmugasundram Source NHS GMS was added to ELAC2.
Source Expert Review Green was added to ELAC2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric or syndromic cardiomyopathy v4.2 CAP2 Achchuthan Shanmugasundram Source NHS GMS was added to CAP2.
Source Expert Review Green was added to CAP2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Cystic kidney disease v5.3 NEK8 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: NEK8.
Cystic kidney disease v5.3 SEC63 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: SEC63.
Tag Q3_23_NHS_review was removed from gene: SEC63.
Cystic kidney disease v5.3 PRKCSH Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PRKCSH.
Tag Q3_23_NHS_review was removed from gene: PRKCSH.
Cystic kidney disease v5.3 SEC63 Arina Puzriakova reviewed gene: SEC63: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cystic kidney disease v5.3 PRKCSH Arina Puzriakova reviewed gene: PRKCSH: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cystic kidney disease v5.3 NEK8 Arina Puzriakova reviewed gene: NEK8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cystic kidney disease v5.2 SEC63 Achchuthan Shanmugasundram Source Expert Review Green was added to SEC63.
Source NHS GMS was added to SEC63.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Cystic kidney disease v5.2 PRKCSH Achchuthan Shanmugasundram Source Expert Review Green was added to PRKCSH.
Source NHS GMS was added to PRKCSH.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Cystic kidney disease v5.2 NEK8 Achchuthan Shanmugasundram Source Expert Review Green was added to NEK8.
Source NHS GMS was added to NEK8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.3 SLC34A3 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SLC34A3.
Unexplained young onset end-stage renal disease v4.3 MOCOS Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: MOCOS.
Unexplained young onset end-stage renal disease v4.3 YRDC Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: YRDC.
Unexplained young onset end-stage renal disease v4.3 WNK4 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: WNK4.
Unexplained young onset end-stage renal disease v4.3 WDR72 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: WDR72.
Unexplained young onset end-stage renal disease v4.3 TULP3 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: TULP3.
Unexplained young onset end-stage renal disease v4.3 TTR Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: TTR.
Unexplained young onset end-stage renal disease v4.3 TRPM6 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: TRPM6.
Unexplained young onset end-stage renal disease v4.3 TPRKB Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: TPRKB.
Unexplained young onset end-stage renal disease v4.3 STRADA Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: STRADA.
Unexplained young onset end-stage renal disease v4.3 SLC5A2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SLC5A2.
Unexplained young onset end-stage renal disease v4.3 SLC4A4 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SLC4A4.
Unexplained young onset end-stage renal disease v4.3 SLC4A1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SLC4A1.
Unexplained young onset end-stage renal disease v4.3 SLC34A1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SLC34A1.
Unexplained young onset end-stage renal disease v4.3 SLC2A2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SLC2A2.
Unexplained young onset end-stage renal disease v4.3 SLC12A3 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SLC12A3.
Unexplained young onset end-stage renal disease v4.3 SLC12A1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SLC12A1.
Unexplained young onset end-stage renal disease v4.3 SEC63 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SEC63.
Unexplained young onset end-stage renal disease v4.3 SCNN1G Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SCNN1G.
Unexplained young onset end-stage renal disease v4.3 SCNN1B Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SCNN1B.
Unexplained young onset end-stage renal disease v4.3 SCNN1A Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SCNN1A.
Unexplained young onset end-stage renal disease v4.3 SARS2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SARS2.
Unexplained young onset end-stage renal disease v4.3 RRAGD Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: RRAGD.
Unexplained young onset end-stage renal disease v4.3 RMND1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: RMND1.
Unexplained young onset end-stage renal disease v4.3 PRKCSH Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: PRKCSH.
Unexplained young onset end-stage renal disease v4.3 PHEX Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: PHEX.
Unexplained young onset end-stage renal disease v4.3 PDSS2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: PDSS2.
Unexplained young onset end-stage renal disease v4.3 NR3C2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: NR3C2.
Unexplained young onset end-stage renal disease v4.3 MAGED2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: MAGED2.
Unexplained young onset end-stage renal disease v4.3 LYZ Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: LYZ.
Unexplained young onset end-stage renal disease v4.3 LCAT Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: LCAT.
Unexplained young onset end-stage renal disease v4.3 KLHL3 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: KLHL3.
Unexplained young onset end-stage renal disease v4.3 KCNJ16 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: KCNJ16.
Unexplained young onset end-stage renal disease v4.3 KCNJ10 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: KCNJ10.
Unexplained young onset end-stage renal disease v4.3 KCNJ1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: KCNJ1.
Unexplained young onset end-stage renal disease v4.3 IFT27 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: IFT27.
Unexplained young onset end-stage renal disease v4.3 IFT172 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: IFT172.
Unexplained young onset end-stage renal disease v4.3 IFT140 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: IFT140.
Unexplained young onset end-stage renal disease v4.3 HPRT1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: HPRT1.
Unexplained young onset end-stage renal disease v4.3 HNF4A Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: HNF4A.
Unexplained young onset end-stage renal disease v4.3 GSN Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: GSN.
Unexplained young onset end-stage renal disease v4.3 GON7 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: GON7.
Unexplained young onset end-stage renal disease v4.3 GNA11 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: GNA11.
Unexplained young onset end-stage renal disease v4.3 FN1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: FN1.
Unexplained young onset end-stage renal disease v4.3 FLCN Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: FLCN.
Unexplained young onset end-stage renal disease v4.3 FGA Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: FGA.
Unexplained young onset end-stage renal disease v4.3 FAM20A Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: FAM20A.
Unexplained young onset end-stage renal disease v4.3 FAH Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: FAH.
Unexplained young onset end-stage renal disease v4.3 DLG5 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: DLG5.
Unexplained young onset end-stage renal disease v4.3 DAAM2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: DAAM2.
Unexplained young onset end-stage renal disease v4.3 CYP24A1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CYP24A1.
Unexplained young onset end-stage renal disease v4.3 CUL3 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CUL3.
Unexplained young onset end-stage renal disease v4.3 CNNM2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CNNM2.
Unexplained young onset end-stage renal disease v4.3 CLDN19 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CLDN19.
Unexplained young onset end-stage renal disease v4.3 CLDN16 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CLDN16.
Unexplained young onset end-stage renal disease v4.3 CLDN10 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CLDN10.
Unexplained young onset end-stage renal disease v4.3 CLCNKB Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CLCNKB.
Unexplained young onset end-stage renal disease v4.3 CFHR2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CFHR2.
Unexplained young onset end-stage renal disease v4.3 CD151 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CD151.
Unexplained young onset end-stage renal disease v4.3 CASR Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CASR.
Unexplained young onset end-stage renal disease v4.3 CA2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CA2.
Unexplained young onset end-stage renal disease v4.3 AVPR2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: AVPR2.
Unexplained young onset end-stage renal disease v4.3 ATP6V1B1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ATP6V1B1.
Unexplained young onset end-stage renal disease v4.3 ATP6V0A4 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ATP6V0A4.
Unexplained young onset end-stage renal disease v4.3 ATP1A1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ATP1A1.
Unexplained young onset end-stage renal disease v4.3 APRT Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: APRT.
Unexplained young onset end-stage renal disease v4.3 APOE Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: APOE.
Unexplained young onset end-stage renal disease v4.3 APOC2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: APOC2.
Unexplained young onset end-stage renal disease v4.3 APOA2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: APOA2.
Unexplained young onset end-stage renal disease v4.3 APOA1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: APOA1.
Unexplained young onset end-stage renal disease v4.3 AP2S1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: AP2S1.
Unexplained young onset end-stage renal disease v4.3 ALG9 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ALG9.
Unexplained young onset end-stage renal disease v4.3 ALG8 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ALG8.
Unexplained young onset end-stage renal disease v4.3 ALG5 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ALG5.
Breast cancer pertinent cancer susceptibility v2.12 CDH1 Achchuthan Shanmugasundram Classified gene: CDH1 as Red List (low evidence)
Breast cancer pertinent cancer susceptibility v2.12 CDH1 Achchuthan Shanmugasundram Gene: cdh1 has been classified as Red List (Low Evidence).
Unexplained young onset end-stage renal disease v4.3 YRDC Arina Puzriakova reviewed gene: YRDC: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 WNK4 Arina Puzriakova reviewed gene: WNK4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 WDR72 Arina Puzriakova reviewed gene: WDR72: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 TULP3 Arina Puzriakova reviewed gene: TULP3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 TTR Arina Puzriakova reviewed gene: TTR: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Unexplained young onset end-stage renal disease v4.3 TRPM6 Arina Puzriakova reviewed gene: TRPM6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 TPRKB Arina Puzriakova reviewed gene: TPRKB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 STRADA Arina Puzriakova reviewed gene: STRADA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 SLC5A2 Arina Puzriakova reviewed gene: SLC5A2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 SLC4A4 Arina Puzriakova reviewed gene: SLC4A4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 SLC4A1 Arina Puzriakova reviewed gene: SLC4A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 SLC34A3 Arina Puzriakova reviewed gene: SLC34A3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 SLC34A1 Arina Puzriakova reviewed gene: SLC34A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 SLC2A2 Arina Puzriakova reviewed gene: SLC2A2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 SLC12A3 Arina Puzriakova reviewed gene: SLC12A3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 SLC12A1 Arina Puzriakova reviewed gene: SLC12A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 SEC63 Arina Puzriakova reviewed gene: SEC63: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 SCNN1G Arina Puzriakova reviewed gene: SCNN1G: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 SCNN1B Arina Puzriakova reviewed gene: SCNN1B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 SCNN1A Arina Puzriakova reviewed gene: SCNN1A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 SARS2 Arina Puzriakova reviewed gene: SARS2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 RRAGD Arina Puzriakova reviewed gene: RRAGD: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 RMND1 Arina Puzriakova reviewed gene: RMND1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 PRKCSH Arina Puzriakova reviewed gene: PRKCSH: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 PHEX Arina Puzriakova reviewed gene: PHEX: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Unexplained young onset end-stage renal disease v4.3 PDSS2 Arina Puzriakova reviewed gene: PDSS2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 NR3C2 Arina Puzriakova reviewed gene: NR3C2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 MOCOS Arina Puzriakova reviewed gene: MOCOS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 MAGED2 Arina Puzriakova reviewed gene: MAGED2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Unexplained young onset end-stage renal disease v4.3 LYZ Arina Puzriakova reviewed gene: LYZ: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 LCAT Arina Puzriakova reviewed gene: LCAT: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 KLHL3 Arina Puzriakova reviewed gene: KLHL3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 KCNJ16 Arina Puzriakova reviewed gene: KCNJ16: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 KCNJ10 Arina Puzriakova reviewed gene: KCNJ10: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 KCNJ1 Arina Puzriakova reviewed gene: KCNJ1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 IFT27 Arina Puzriakova reviewed gene: IFT27: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 IFT172 Arina Puzriakova reviewed gene: IFT172: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 IFT140 Arina Puzriakova reviewed gene: IFT140: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 HPRT1 Arina Puzriakova reviewed gene: HPRT1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Unexplained young onset end-stage renal disease v4.3 HNF4A Arina Puzriakova reviewed gene: HNF4A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Unexplained young onset end-stage renal disease v4.3 GSN Arina Puzriakova reviewed gene: GSN: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 GON7 Arina Puzriakova reviewed gene: GON7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 GNA11 Arina Puzriakova reviewed gene: GNA11: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 FN1 Arina Puzriakova reviewed gene: FN1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 FLCN Arina Puzriakova reviewed gene: FLCN: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 FGA Arina Puzriakova reviewed gene: FGA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 FAM20A Arina Puzriakova reviewed gene: FAM20A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 FAH Arina Puzriakova reviewed gene: FAH: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 DLG5 Arina Puzriakova reviewed gene: DLG5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 DAAM2 Arina Puzriakova reviewed gene: DAAM2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 CYP24A1 Arina Puzriakova reviewed gene: CYP24A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 CUL3 Arina Puzriakova reviewed gene: CUL3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 CNNM2 Arina Puzriakova reviewed gene: CNNM2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 CLDN19 Arina Puzriakova reviewed gene: CLDN19: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 CLDN16 Arina Puzriakova reviewed gene: CLDN16: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 CLDN10 Arina Puzriakova reviewed gene: CLDN10: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 CLCNKB Arina Puzriakova reviewed gene: CLCNKB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 CFHR2 Arina Puzriakova reviewed gene: CFHR2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 CD151 Arina Puzriakova reviewed gene: CD151: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 CASR Arina Puzriakova reviewed gene: CASR: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 CA2 Arina Puzriakova reviewed gene: CA2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 AVPR2 Arina Puzriakova reviewed gene: AVPR2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Unexplained young onset end-stage renal disease v4.3 ATP6V1B1 Arina Puzriakova reviewed gene: ATP6V1B1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 ATP6V0A4 Arina Puzriakova reviewed gene: ATP6V0A4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 ATP1A1 Arina Puzriakova reviewed gene: ATP1A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 APRT Arina Puzriakova reviewed gene: APRT: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 APOE Arina Puzriakova reviewed gene: APOE: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 APOC2 Arina Puzriakova reviewed gene: APOC2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 APOA2 Arina Puzriakova reviewed gene: APOA2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 APOA1 Arina Puzriakova reviewed gene: APOA1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 AP2S1 Arina Puzriakova reviewed gene: AP2S1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 ALG9 Arina Puzriakova reviewed gene: ALG9: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 ALG8 Arina Puzriakova reviewed gene: ALG8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Unexplained young onset end-stage renal disease v4.3 ALG5 Arina Puzriakova reviewed gene: ALG5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Unexplained young onset end-stage renal disease v4.2 YRDC Achchuthan Shanmugasundram Source Expert Review Green was added to YRDC.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 WNK4 Achchuthan Shanmugasundram Source Expert Review Green was added to WNK4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 WDR72 Achchuthan Shanmugasundram Source Expert Review Green was added to WDR72.
Source NHS GMS was added to WDR72.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 TULP3 Achchuthan Shanmugasundram Source Expert Review Green was added to TULP3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 TTR Achchuthan Shanmugasundram Source Expert Review Green was added to TTR.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 TRPM6 Achchuthan Shanmugasundram Source Expert Review Green was added to TRPM6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 TPRKB Achchuthan Shanmugasundram Source Expert Review Green was added to TPRKB.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 STRADA Achchuthan Shanmugasundram Source Expert Review Green was added to STRADA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 SLC5A2 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC5A2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 SLC4A4 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC4A4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 SLC4A1 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC4A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 SLC34A3 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC34A3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 SLC34A1 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC34A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 SLC2A2 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC2A2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 SLC12A3 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC12A3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 SLC12A1 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC12A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 SEC63 Achchuthan Shanmugasundram Source Expert Review Green was added to SEC63.
Source NHS GMS was added to SEC63.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 SCNN1G Achchuthan Shanmugasundram Source Expert Review Green was added to SCNN1G.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 SCNN1B Achchuthan Shanmugasundram Source Expert Review Green was added to SCNN1B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 SCNN1A Achchuthan Shanmugasundram Source Expert Review Green was added to SCNN1A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 SARS2 Achchuthan Shanmugasundram Source Expert Review Green was added to SARS2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 RRAGD Achchuthan Shanmugasundram Source Expert Review Green was added to RRAGD.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 RMND1 Achchuthan Shanmugasundram Source Expert Review Green was added to RMND1.
Source NHS GMS was added to RMND1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 PRKCSH Achchuthan Shanmugasundram Source Expert Review Green was added to PRKCSH.
Source NHS GMS was added to PRKCSH.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 PHEX Achchuthan Shanmugasundram Source Expert Review Green was added to PHEX.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 PDSS2 Achchuthan Shanmugasundram Source Expert Review Green was added to PDSS2.
Source NHS GMS was added to PDSS2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 NR3C2 Achchuthan Shanmugasundram Source Expert Review Green was added to NR3C2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 MOCOS Achchuthan Shanmugasundram Source Expert Review Green was added to MOCOS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 MAGED2 Achchuthan Shanmugasundram Source Expert Review Green was added to MAGED2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 LYZ Achchuthan Shanmugasundram Source Expert Review Green was added to LYZ.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 LCAT Achchuthan Shanmugasundram Source Expert Review Green was added to LCAT.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 KLHL3 Achchuthan Shanmugasundram Source Expert Review Green was added to KLHL3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 KCNJ16 Achchuthan Shanmugasundram Source Expert Review Green was added to KCNJ16.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 KCNJ10 Achchuthan Shanmugasundram Source Expert Review Green was added to KCNJ10.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 KCNJ1 Achchuthan Shanmugasundram Source Expert Review Green was added to KCNJ1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 IFT27 Achchuthan Shanmugasundram Source Expert Review Green was added to IFT27.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 IFT172 Achchuthan Shanmugasundram Source Expert Review Green was added to IFT172.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 IFT140 Achchuthan Shanmugasundram Source Expert Review Green was added to IFT140.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 HPRT1 Achchuthan Shanmugasundram Source Expert Review Green was added to HPRT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 HNF4A Achchuthan Shanmugasundram Source Expert Review Green was added to HNF4A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 GSN Achchuthan Shanmugasundram Source Expert Review Green was added to GSN.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 GON7 Achchuthan Shanmugasundram Source Expert Review Green was added to GON7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 GNA11 Achchuthan Shanmugasundram Source Expert Review Green was added to GNA11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 FN1 Achchuthan Shanmugasundram Source Expert Review Green was added to FN1.
Source NHS GMS was added to FN1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 FLCN Achchuthan Shanmugasundram Source Expert Review Green was added to FLCN.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 FGA Achchuthan Shanmugasundram Source Expert Review Green was added to FGA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 FAM20A Achchuthan Shanmugasundram Source Expert Review Green was added to FAM20A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 FAH Achchuthan Shanmugasundram Source Expert Review Green was added to FAH.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 DLG5 Achchuthan Shanmugasundram Source Expert Review Green was added to DLG5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 DAAM2 Achchuthan Shanmugasundram Source Expert Review Green was added to DAAM2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 CYP24A1 Achchuthan Shanmugasundram Source Expert Review Green was added to CYP24A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 CUL3 Achchuthan Shanmugasundram Source Expert Review Green was added to CUL3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 CNNM2 Achchuthan Shanmugasundram Source Expert Review Green was added to CNNM2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 CLDN19 Achchuthan Shanmugasundram Source Expert Review Green was added to CLDN19.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 CLDN16 Achchuthan Shanmugasundram Source Expert Review Green was added to CLDN16.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 CLDN10 Achchuthan Shanmugasundram Source Expert Review Green was added to CLDN10.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 CLCNKB Achchuthan Shanmugasundram Source Expert Review Green was added to CLCNKB.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 CFHR2 Achchuthan Shanmugasundram Source Expert Review Green was added to CFHR2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 CD151 Achchuthan Shanmugasundram Source Expert Review Green was added to CD151.
Source NHS GMS was added to CD151.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 CASR Achchuthan Shanmugasundram Source Expert Review Green was added to CASR.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 CA2 Achchuthan Shanmugasundram Source Expert Review Green was added to CA2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 AVPR2 Achchuthan Shanmugasundram Source Expert Review Green was added to AVPR2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 ATP6V1B1 Achchuthan Shanmugasundram Source Expert Review Green was added to ATP6V1B1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 ATP6V0A4 Achchuthan Shanmugasundram Source Expert Review Green was added to ATP6V0A4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 ATP1A1 Achchuthan Shanmugasundram Source Expert Review Green was added to ATP1A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 APRT Achchuthan Shanmugasundram Source Expert Review Green was added to APRT.
Source NHS GMS was added to APRT.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 APOE Achchuthan Shanmugasundram Source Expert Review Green was added to APOE.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 APOC2 Achchuthan Shanmugasundram Source Expert Review Green was added to APOC2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 APOA2 Achchuthan Shanmugasundram Source Expert Review Green was added to APOA2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 APOA1 Achchuthan Shanmugasundram Source Expert Review Green was added to APOA1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 AP2S1 Achchuthan Shanmugasundram Source Expert Review Green was added to AP2S1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 ALG9 Achchuthan Shanmugasundram Source Expert Review Green was added to ALG9.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 ALG8 Achchuthan Shanmugasundram Source Expert Review Green was added to ALG8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 ALG5 Achchuthan Shanmugasundram Source Expert Review Green was added to ALG5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Amelogenesis imperfecta v3.3 AMBN Claire Smith edited their review of gene: AMBN: Added comment: PMID: 38058155 identifies AMBN variants that appear to cause disease in an autosomal dominant fashion.
One family has a dominant family history spanning 4 generations, and the likely causative variant in this family was also identified as monoallelic/heterozygous in 2 other apparently unrelated individuals with isolated AI.; Changed publications to: PMID: 24858907, 26502894, 38058155; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v3.79 SMG8 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: SMG8.
Tag Q4_23_NHS_review was removed from gene: SMG8.
Structural eye disease v3.79 SLC25A24 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: SLC25A24.
Tag Q4_23_NHS_review was removed from gene: SLC25A24.
Structural eye disease v3.79 RHOA Arina Puzriakova Tag Q4_23_promote_green was removed from gene: RHOA.
Tag Q4_23_NHS_review was removed from gene: RHOA.
Structural eye disease v3.79 OFD1 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: OFD1.
Tag Q3_23_NHS_review was removed from gene: OFD1.
Breast cancer pertinent cancer susceptibility v2.11 CDH1 Achchuthan Shanmugasundram Classified gene: CDH1 as Amber List (moderate evidence)
Breast cancer pertinent cancer susceptibility v2.11 CDH1 Achchuthan Shanmugasundram Gene: cdh1 has been classified as Amber List (Moderate Evidence).
Structural eye disease v3.79 NUP188 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: NUP188.
Tag Q4_23_NHS_review was removed from gene: NUP188.
Structural eye disease v3.79 MIR204 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: MIR204.
Tag Q3_23_NHS_review was removed from gene: MIR204.
Breast cancer pertinent cancer susceptibility v2.10 CDH1 Achchuthan Shanmugasundram Classified gene: CDH1 as Red List (low evidence)
Breast cancer pertinent cancer susceptibility v2.10 CDH1 Achchuthan Shanmugasundram Gene: cdh1 has been classified as Red List (Low Evidence).
Breast cancer pertinent cancer susceptibility v2.9 CDH1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: CDH1.
Tag Q3_23_expert_review was removed from gene: CDH1.
Structural eye disease v3.79 KIF11 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: KIF11.
Tag Q4_23_NHS_review was removed from gene: KIF11.
Structural eye disease v3.79 KIAA0586 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: KIAA0586.
Tag Q4_23_NHS_review was removed from gene: KIAA0586.
Structural eye disease v3.79 KDM6A Arina Puzriakova Tag Q4_23_promote_green was removed from gene: KDM6A.
Tag Q4_23_NHS_review was removed from gene: KDM6A.
Structural eye disease v3.79 EPHA2 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: EPHA2.
Tag Q4_23_MOI was removed from gene: EPHA2.
Tag Q4_23_NHS_review was removed from gene: EPHA2.
Amelogenesis imperfecta v3.3 PLXNB2 Claire Smith changed review comment from: PMID: 38458752 Smith et al. (in press) report 8 patients in 6 families with rare biallelic pathogenic variants in PLXNB2 as a cause of a new autosomal recessive, phenotypically diverse syndrome with AI and sensorineural hearing loss as core features. Intellectual disability, ocular disease, ear developmental abnormalities and lymphoedema were also present in multiple cases.
Sources: Literature, Expert Review; to: PMID: 38458752 Smith et al. (in press) report 8 patients in 6 families with rare biallelic pathogenic variants in PLXNB2 as a cause of a new autosomal recessive, phenotypically diverse syndrome with AI and sensorineural hearing loss as core features. Intellectual disability, ocular disease, ear developmental abnormalities and lymphoedema were also present in multiple cases.
Sources: Literature, Expert Review

Personal communication with Roland Friedel and Christian Junquiera-Alves regarding their findings in their Plxnb2-/- mouse model after publication of human patients with PLXNB2 variants: "We had made also initial observations in the PB2 KO mouse on cochlear defects and tooth malformations that looked interesting, but we did not follow up as I focused on cerebellar development. Now these findings look in retrospect much more exciting considering your data."
Structural eye disease v3.79 CRYBB2 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: CRYBB2.
Tag Q4_23_NHS_review was removed from gene: CRYBB2.
Structural eye disease v3.79 BMPR1B Arina Puzriakova Tag Q4_23_promote_green was removed from gene: BMPR1B.
Tag Q4_23_NHS_review was removed from gene: BMPR1B.
Structural eye disease v3.79 ARHGAP35 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: ARHGAP35.
Tag Q4_23_NHS_review was removed from gene: ARHGAP35.
Structural eye disease v3.79 ANK3 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: ANK3.
Tag Q4_23_NHS_review was removed from gene: ANK3.
Structural eye disease v3.79 ALX1 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: ALX1.
Tag Q3_23_NHS_review was removed from gene: ALX1.
Structural eye disease v3.79 SMG8 Arina Puzriakova reviewed gene: SMG8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v3.79 SLC25A24 Arina Puzriakova reviewed gene: SLC25A24: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v3.79 RHOA Arina Puzriakova reviewed gene: RHOA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Structural eye disease v3.79 OFD1 Arina Puzriakova reviewed gene: OFD1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Structural eye disease v3.79 NUP188 Arina Puzriakova reviewed gene: NUP188: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v3.79 MIR204 Arina Puzriakova reviewed gene: MIR204: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v3.79 KIF11 Arina Puzriakova reviewed gene: KIF11: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v3.79 KIAA0586 Arina Puzriakova reviewed gene: KIAA0586: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v3.79 KDM6A Arina Puzriakova reviewed gene: KDM6A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Structural eye disease v3.79 EPHA2 Arina Puzriakova reviewed gene: EPHA2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v3.79 CRYBB2 Arina Puzriakova reviewed gene: CRYBB2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v3.79 BMPR1B Arina Puzriakova reviewed gene: BMPR1B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v3.79 ARHGAP35 Arina Puzriakova reviewed gene: ARHGAP35: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v3.79 ANK3 Arina Puzriakova reviewed gene: ANK3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v3.79 ALX1 Arina Puzriakova reviewed gene: ALX1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v3.78 SMG8 Arina Puzriakova Source NHS GMS was added to SMG8.
Source Expert Review Green was added to SMG8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v3.78 SLC25A24 Arina Puzriakova Source Expert Review Green was added to SLC25A24.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v3.78 RHOA Arina Puzriakova Source NHS GMS was added to RHOA.
Source Expert Review Green was added to RHOA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v3.78 OFD1 Arina Puzriakova Source Expert Review Green was added to OFD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v3.78 NUP188 Arina Puzriakova Source NHS GMS was added to NUP188.
Source Expert Review Green was added to NUP188.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v3.78 MIR204 Arina Puzriakova Source Expert Review Green was added to MIR204.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v3.78 KIF11 Arina Puzriakova Source Expert Review Green was added to KIF11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v3.78 KIAA0586 Arina Puzriakova Source NHS GMS was added to KIAA0586.
Source Expert Review Green was added to KIAA0586.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v3.78 KDM6A Arina Puzriakova Source Expert Review Green was added to KDM6A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v3.78 EPHA2 Arina Puzriakova Source Expert Review Green was added to EPHA2.
Mode of inheritance for gene EPHA2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v3.78 CRYBB2 Arina Puzriakova Source Expert Review Green was added to CRYBB2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v3.78 BMPR1B Arina Puzriakova Source NHS GMS was added to BMPR1B.
Source Expert Review Green was added to BMPR1B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v3.78 ARHGAP35 Arina Puzriakova Source NHS GMS was added to ARHGAP35.
Source Expert Review Green was added to ARHGAP35.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v3.78 ANK3 Arina Puzriakova Source NHS GMS was added to ANK3.
Source Expert Review Green was added to ANK3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v3.78 ALX1 Arina Puzriakova Source Expert Review Green was added to ALX1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Breast cancer pertinent cancer susceptibility v2.9 ATRIP Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ATRIP.
Tag Q4_23_expert_review was removed from gene: ATRIP.
Amelogenesis imperfecta v3.3 PLXNB2 Claire Smith gene: PLXNB2 was added
gene: PLXNB2 was added to Amelogenesis imperfecta. Sources: Literature,Expert Review
Mode of inheritance for gene: PLXNB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLXNB2 were set to PMID: 38458752
Phenotypes for gene: PLXNB2 were set to Amelogenesis imperfecta; sensorineural hearing loss
Penetrance for gene: PLXNB2 were set to unknown
Review for gene: PLXNB2 was set to GREEN
Added comment: PMID: 38458752 Smith et al. (in press) report 8 patients in 6 families with rare biallelic pathogenic variants in PLXNB2 as a cause of a new autosomal recessive, phenotypically diverse syndrome with AI and sensorineural hearing loss as core features. Intellectual disability, ocular disease, ear developmental abnormalities and lymphoedema were also present in multiple cases.
Sources: Literature, Expert Review
Breast cancer pertinent cancer susceptibility v2.9 CDH1 Arina Puzriakova edited their review of gene: CDH1: Added comment: After NHS Genomic Medicine Service consideration, this gene has not been made Green and has been rated as Red. Additional comments from reviewing GLHs: 'There is a well established association of this gene withpredisposition to lobular breast cancer, but it presents huge problems when it is identified outside the context of a relevant family history. The UK Cancer genetics community do not want to add this gene to any general breast cancer susceptibility panels hence are extremely reluctant to test this gene outside of the already existing R215 criteria'; Changed rating: RED; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Breast cancer pertinent cancer susceptibility v2.9 ATRIP Arina Puzriakova edited their review of gene: ATRIP: Added comment: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Amber. Additional comments from reviewing GLHs: 'Whilst the referenced paper does support an association with breast cancer, more studies are needed before we can consider adding this gene to any panel. The referenced paper itself comments that further replication in larger datasets is necessary to provide figures on lifetime risk, to better define the association with breast cancer and the clinic-pathological characteristics of tumors in variant carriers . Without this important information, it is too early to add the gene to a breast cancer susceptibility panel'; Changed rating: AMBER; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Retinal disorders v5.4 RPE65 Arina Puzriakova Tag Q4_23_MOI was removed from gene: RPE65.
Retinal disorders v5.4 PYGM Arina Puzriakova Tag Q3_23_promote_green was removed from gene: PYGM.
Tag Q3_23_NHS_review was removed from gene: PYGM.
Retinal disorders v5.4 NBAS Arina Puzriakova Tag Q3_23_promote_green was removed from gene: NBAS.
Tag Q3_23_NHS_review was removed from gene: NBAS.
Retinal disorders v5.4 MVK Arina Puzriakova Tag Q4_23_promote_green was removed from gene: MVK.
Tag Q4_23_NHS_review was removed from gene: MVK.
Retinal disorders v5.4 MPDZ Arina Puzriakova Tag Q3_23_promote_green was removed from gene: MPDZ.
Tag Q3_23_NHS_review was removed from gene: MPDZ.
Retinal disorders v5.4 MIR204 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: MIR204.
Tag Q3_23_NHS_review was removed from gene: MIR204.
Retinal disorders v5.4 MCOLN1 Arina Puzriakova Phenotypes for gene: MCOLN1 were changed from to Mucolipidosis IV, OMIM:252650
Retinal disorders v5.3 MCOLN1 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: MCOLN1.
Retinal disorders v5.3 DYNC2H1 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: DYNC2H1.
Retinal disorders v5.3 CTNND1 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: CTNND1.
Retinal disorders v5.3 CFAP20 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: CFAP20.
Retinal disorders v5.3 RPE65 Arina Puzriakova Mode of inheritance for gene RPE65 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Retinal disorders v5.3 PYGM Arina Puzriakova Source NHS GMS was added to PYGM.
Source Expert Review Green was added to PYGM.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v5.3 NBAS Arina Puzriakova Source Expert Review Green was added to NBAS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v5.3 MVK Arina Puzriakova Source Expert Review Green was added to MVK.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v5.3 MPDZ Arina Puzriakova Source NHS GMS was added to MPDZ.
Source Expert Review Green was added to MPDZ.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v5.3 MIR204 Arina Puzriakova Source Expert Review Green was added to MIR204.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v5.3 MCOLN1 Arina Puzriakova Source NHS GMS was added to MCOLN1.
Source Expert Review Green was added to MCOLN1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v5.3 DYNC2H1 Arina Puzriakova Source NHS GMS was added to DYNC2H1.
Source Expert Review Green was added to DYNC2H1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v5.3 CTNND1 Arina Puzriakova Source NHS GMS was added to CTNND1.
Source Expert Review Green was added to CTNND1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v5.3 CFAP20 Arina Puzriakova Source NHS GMS was added to CFAP20.
Source Expert Review Green was added to CFAP20.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v5.2 RPE65 Arina Puzriakova edited their review of gene: RPE65: Added comment: The mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Retinal disorders v5.2 PYGM Arina Puzriakova reviewed gene: PYGM: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v5.2 NBAS Arina Puzriakova reviewed gene: NBAS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v5.2 MVK Arina Puzriakova reviewed gene: MVK: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v5.2 MPDZ Arina Puzriakova reviewed gene: MPDZ: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v5.2 MIR204 Arina Puzriakova reviewed gene: MIR204: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Retinal disorders v5.2 MCOLN1 Arina Puzriakova reviewed gene: MCOLN1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v5.2 DYNC2H1 Arina Puzriakova reviewed gene: DYNC2H1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v5.2 CTNND1 Arina Puzriakova reviewed gene: CTNND1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Retinal disorders v5.2 CFAP20 Arina Puzriakova reviewed gene: CFAP20: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 SCN8A Achchuthan Shanmugasundram Tag for-review was removed from gene: SCN8A.
Tag to_be_confirmed_NHSE was removed from gene: SCN8A.
Early onset or syndromic epilepsy v5.6 CACNB4 Achchuthan Shanmugasundram Tag Q4_23_demote_red was removed from gene: CACNB4.
Tag Q4_23_expert_review was removed from gene: CACNB4.
Early onset or syndromic epilepsy v5.6 ZBTB47 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ZBTB47.
Early onset or syndromic epilepsy v5.6 TRIT1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: TRIT1.
Early onset or syndromic epilepsy v5.6 SHQ1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SHQ1.
Early onset or syndromic epilepsy v5.6 PTCD3 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: PTCD3.
Early onset or syndromic epilepsy v5.6 PLA2G6 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: PLA2G6.
Early onset or syndromic epilepsy v5.6 PIGM Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: PIGM.
Early onset or syndromic epilepsy v5.6 MAST4 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: MAST4.
Early onset or syndromic epilepsy v5.6 HECTD4 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: HECTD4.
Early onset or syndromic epilepsy v5.6 ASL Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ASL.
Tag Q4_23_NHS_review was removed from gene: ASL.
Early onset or syndromic epilepsy v5.6 ARF3 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ARF3.
Bilateral congenital or childhood onset cataracts v4.14 LETM1 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: LETM1.
Tag Q3_23_MOI was removed from gene: LETM1.
Bilateral congenital or childhood onset cataracts v4.14 EPHA2 Arina Puzriakova Tag Q4_23_MOI was removed from gene: EPHA2.
Early onset or syndromic epilepsy v5.6 AGO1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: AGO1.
Bilateral congenital or childhood onset cataracts v4.14 LETM1 Arina Puzriakova reviewed gene: LETM1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bilateral congenital or childhood onset cataracts v4.14 EPHA2 Arina Puzriakova reviewed gene: EPHA2: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Bilateral congenital or childhood onset cataracts v4.13 LETM1 Arina Puzriakova Source NHS GMS was added to LETM1.
Source Expert Review Green was added to LETM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Bilateral congenital or childhood onset cataracts v4.13 EPHA2 Arina Puzriakova Source NHS GMS was added to EPHA2.
Mode of inheritance for gene EPHA2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 U2AF2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: U2AF2.
Early onset or syndromic epilepsy v5.6 TMEM63B Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: TMEM63B.
White matter disorders and cerebral calcification - narrow panel v4.3 PPFIBP1 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: PPFIBP1.
White matter disorders and cerebral calcification - narrow panel v4.3 ESAM Arina Puzriakova Tag Q3_23_promote_green was removed from gene: ESAM.
Early onset or syndromic epilepsy v5.6 RAB5C Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: RAB5C.
Early onset or syndromic epilepsy v5.6 PPP1R3F Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PPP1R3F.
Early onset or syndromic epilepsy v5.6 PIP5K1C Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PIP5K1C.
White matter disorders and cerebral calcification - narrow panel v4.3 PPFIBP1 Arina Puzriakova reviewed gene: PPFIBP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v4.3 ESAM Arina Puzriakova reviewed gene: ESAM: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 PABPC1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PABPC1.
Tag Q3_23_MOI was removed from gene: PABPC1.
White matter disorders and cerebral calcification - narrow panel v4.2 PPFIBP1 Arina Puzriakova Source Expert Review Green was added to PPFIBP1.
Source NHS GMS was added to PPFIBP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v4.2 ESAM Arina Puzriakova Source Expert Review Green was added to ESAM.
Source NHS GMS was added to ESAM.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.6 LETM1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: LETM1.
Tag Q3_23_MOI was removed from gene: LETM1.
Early onset or syndromic epilepsy v5.6 KDM6B Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: KDM6B.
Early onset or syndromic epilepsy v5.6 KCNH5 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: KCNH5.
Intellectual disability v6.9 DPP6 Arina Puzriakova Phenotypes for gene: DPP6 were changed from autosomal dominant microcephaly and mental retardation; Mental retardation, autosomal dominant 33, 616311 to Intellectual developmental disorder, autosomal dominant 33, OMIM:616311
Early onset or syndromic epilepsy v5.6 ESAM Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: ESAM.
Early onset or syndromic epilepsy v5.6 EIF4A2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: EIF4A2.
Early onset or syndromic epilepsy v5.6 DNAJC6 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: DNAJC6.
Severe microcephaly v5.7 DPP6 Arina Puzriakova Phenotypes for gene: DPP6 were changed from MCPH; primary microcephaly; autosomal dominant microcephaly and mental retardation; Mental retardation, autosomal dominant 33, 616311 to Intellectual developmental disorder, autosomal dominant 33, OMIM:616311
Intellectual disability v6.8 TTI1 Arina Puzriakova Added comment: Comment on phenotypes: Relevant phenotype now listed in OMIM (Neurodevelopmental disorder with microcephaly and movement abnormalities, OMIM:620445)
Intellectual disability v6.8 TTI1 Arina Puzriakova Phenotypes for gene: TTI1 were changed from neurodevelopmental disorder with microcephaly to Neurodevelopmental disorder with microcephaly and movement abnormalities, OMIM:620445
Severe microcephaly v5.6 DPP6 Arina Puzriakova Tag to_be_confirmed_NHSE was removed from gene: DPP6.
Severe microcephaly v5.6 TTI1 Arina Puzriakova Added comment: Comment on phenotypes: Relevant phenotype now listed in OMIM (Neurodevelopmental disorder with microcephaly and movement abnormalities, OMIM:620445)
Severe microcephaly v5.6 TTI1 Arina Puzriakova Phenotypes for gene: TTI1 were changed from neurodevelopmental disorder with microcephaly to Neurodevelopmental disorder with microcephaly and movement abnormalities, OMIM:620445
Severe microcephaly v5.5 TTI1 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: TTI1.
Severe microcephaly v5.5 PPFIBP1 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: PPFIBP1.
Early onset or syndromic epilepsy v5.6 CRELD1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: CRELD1.
Severe microcephaly v5.5 NSD2 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: NSD2.
Severe microcephaly v5.5 MECP2 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: MECP2.
Severe microcephaly v5.5 KMT2B Arina Puzriakova Tag Q4_23_promote_green was removed from gene: KMT2B.
Severe microcephaly v5.5 BUB1 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: BUB1.
Severe microcephaly v5.5 ATP6V0C Arina Puzriakova Tag Q3_23_promote_green was removed from gene: ATP6V0C.
Tag Q3_23_NHS_review was removed from gene: ATP6V0C.
Severe microcephaly v5.5 ARF3 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: ARF3.
Early onset or syndromic epilepsy v5.6 CNOT9 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: CNOT9.
Early onset or syndromic epilepsy v5.6 ATP6V0C Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: ATP6V0C.
Tag Q3_23_NHS_review was removed from gene: ATP6V0C.
Severe microcephaly v5.5 TTI1 Arina Puzriakova Source Expert Review Green was added to TTI1.
Source NHS GMS was added to TTI1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v5.5 PPFIBP1 Arina Puzriakova Source Expert Review Green was added to PPFIBP1.
Source NHS GMS was added to PPFIBP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v5.5 NSD2 Arina Puzriakova Source Expert Review Green was added to NSD2.
Source NHS GMS was added to NSD2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v5.5 MECP2 Arina Puzriakova Source Expert Review Green was added to MECP2.
Source NHS GMS was added to MECP2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v5.5 KMT2B Arina Puzriakova Source Expert Review Green was added to KMT2B.
Source NHS GMS was added to KMT2B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v5.5 DPP6 Arina Puzriakova Source Expert Review Amber was added to DPP6.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Severe microcephaly v5.5 BUB1 Arina Puzriakova Source Expert Review Green was added to BUB1.
Source NHS GMS was added to BUB1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v5.5 ATP6V0C Arina Puzriakova Source Expert Review Green was added to ATP6V0C.
Source NHS GMS was added to ATP6V0C.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v5.5 ARF3 Arina Puzriakova Source Expert Review Green was added to ARF3.
Source NHS GMS was added to ARF3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v5.4 DPP6 Arina Puzriakova reviewed gene: DPP6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v5.4 TTI1 Arina Puzriakova reviewed gene: TTI1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly v5.4 PPFIBP1 Arina Puzriakova reviewed gene: PPFIBP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly v5.4 NSD2 Arina Puzriakova reviewed gene: NSD2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Severe microcephaly v5.4 MECP2 Arina Puzriakova reviewed gene: MECP2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Severe microcephaly v5.4 KMT2B Arina Puzriakova commented on gene: KMT2B: The rating of this gene has been updated to Green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown' following NHS Genomic Medicine Service approval.
Severe microcephaly v5.4 BUB1 Arina Puzriakova edited their review of gene: BUB1: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly v5.4 ATP6V0C Arina Puzriakova reviewed gene: ATP6V0C: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Severe microcephaly v5.4 ARF3 Arina Puzriakova reviewed gene: ARF3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v5.6 SLC5A6 Eleanor Williams reviewed gene: SLC5A6: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Early onset or syndromic epilepsy v5.6 ZBTB47 Eleanor Williams reviewed gene: ZBTB47: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v5.6 U2AF2 Eleanor Williams reviewed gene: U2AF2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v5.6 TRIT1 Eleanor Williams edited their review of gene: TRIT1: Added comment: The rating of this gene has been updated togreenand the mode of inheritance set to'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Early onset or syndromic epilepsy v5.6 TMEM63B Eleanor Williams reviewed gene: TMEM63B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v5.6 SHQ1 Eleanor Williams reviewed gene: SHQ1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 SCN8A Eleanor Williams reviewed gene: SCN8A: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 RAB5C Eleanor Williams reviewed gene: RAB5C: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v5.6 PTCD3 Eleanor Williams reviewed gene: PTCD3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 PPP1R3F Eleanor Williams reviewed gene: PPP1R3F: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Early onset or syndromic epilepsy v5.6 PLA2G6 Eleanor Williams reviewed gene: PLA2G6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 PIP5K1C Eleanor Williams reviewed gene: PIP5K1C: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v5.6 PIGM Eleanor Williams reviewed gene: PIGM: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 PABPC1 Eleanor Williams reviewed gene: PABPC1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 MAST4 Eleanor Williams reviewed gene: MAST4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v5.6 LETM1 Eleanor Williams reviewed gene: LETM1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 KDM6B Eleanor Williams reviewed gene: KDM6B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v5.6 KCNH5 Eleanor Williams reviewed gene: KCNH5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v5.6 HECTD4 Eleanor Williams reviewed gene: HECTD4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 ESAM Eleanor Williams reviewed gene: ESAM: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 EIF4A2 Eleanor Williams reviewed gene: EIF4A2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 DNAJC6 Eleanor Williams reviewed gene: DNAJC6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 CRELD1 Eleanor Williams reviewed gene: CRELD1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 CNOT9 Eleanor Williams reviewed gene: CNOT9: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v5.6 CACNB4 Eleanor Williams reviewed gene: CACNB4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Early onset or syndromic epilepsy v5.6 ATP6V0C Eleanor Williams reviewed gene: ATP6V0C: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v5.6 ASL Eleanor Williams edited their review of gene: ASL: Added comment: The rating of this gene has been updated togreenand the mode of inheritance set to'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 ARF3 Eleanor Williams reviewed gene: ARF3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v5.6 AGO1 Eleanor Williams reviewed gene: AGO1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v5.5 ZBTB47 Achchuthan Shanmugasundram Source NHS GMS was added to ZBTB47.
Source Expert Review Green was added to ZBTB47.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 U2AF2 Achchuthan Shanmugasundram Source NHS GMS was added to U2AF2.
Source Expert Review Green was added to U2AF2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 TRIT1 Achchuthan Shanmugasundram Source NHS GMS was added to TRIT1.
Source Expert Review Green was added to TRIT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 TMEM63B Achchuthan Shanmugasundram Source NHS GMS was added to TMEM63B.
Source Expert Review Green was added to TMEM63B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 SLC5A6 Achchuthan Shanmugasundram Source NHS GMS was added to SLC5A6.
Early onset or syndromic epilepsy v5.5 SHQ1 Achchuthan Shanmugasundram Source NHS GMS was added to SHQ1.
Source Expert Review Green was added to SHQ1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 SCN8A Achchuthan Shanmugasundram Mode of inheritance for gene SCN8A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.5 RAB5C Achchuthan Shanmugasundram Source NHS GMS was added to RAB5C.
Source Expert Review Green was added to RAB5C.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 PTCD3 Achchuthan Shanmugasundram Source NHS GMS was added to PTCD3.
Source Expert Review Green was added to PTCD3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 PPP1R3F Achchuthan Shanmugasundram Source NHS GMS was added to PPP1R3F.
Source Expert Review Green was added to PPP1R3F.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 PLA2G6 Achchuthan Shanmugasundram Source NHS GMS was added to PLA2G6.
Source Expert Review Green was added to PLA2G6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 PIP5K1C Achchuthan Shanmugasundram Source NHS GMS was added to PIP5K1C.
Source Expert Review Green was added to PIP5K1C.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 PIGM Achchuthan Shanmugasundram Source Expert Review Green was added to PIGM.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 PABPC1 Achchuthan Shanmugasundram Source NHS GMS was added to PABPC1.
Source Expert Review Green was added to PABPC1.
Mode of inheritance for gene PABPC1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 MAST4 Achchuthan Shanmugasundram Source NHS GMS was added to MAST4.
Source Expert Review Green was added to MAST4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 LETM1 Achchuthan Shanmugasundram Source NHS GMS was added to LETM1.
Source Expert Review Green was added to LETM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 KDM6B Achchuthan Shanmugasundram Source Expert Review Green was added to KDM6B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 KCNH5 Achchuthan Shanmugasundram Source Expert Review Green was added to KCNH5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 HECTD4 Achchuthan Shanmugasundram Source Expert Review Green was added to HECTD4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 ESAM Achchuthan Shanmugasundram Source NHS GMS was added to ESAM.
Source Expert Review Green was added to ESAM.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 EIF4A2 Achchuthan Shanmugasundram Source NHS GMS was added to EIF4A2.
Source Expert Review Green was added to EIF4A2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 DNAJC6 Achchuthan Shanmugasundram Source Expert Review Green was added to DNAJC6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 CRELD1 Achchuthan Shanmugasundram Source NHS GMS was added to CRELD1.
Source Expert Review Green was added to CRELD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 CNOT9 Achchuthan Shanmugasundram Source NHS GMS was added to CNOT9.
Source Expert Review Green was added to CNOT9.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 CACNB4 Achchuthan Shanmugasundram Source Expert Review Red was added to CACNB4.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Early onset or syndromic epilepsy v5.5 ATP6V0C Achchuthan Shanmugasundram Source NHS GMS was added to ATP6V0C.
Source Expert Review Green was added to ATP6V0C.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 ASL Achchuthan Shanmugasundram Source NHS GMS was added to ASL.
Source Expert Review Green was added to ASL.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 ARF3 Achchuthan Shanmugasundram Source NHS GMS was added to ARF3.
Source Expert Review Green was added to ARF3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 AGO1 Achchuthan Shanmugasundram Source NHS GMS was added to AGO1.
Source Expert Review Green was added to AGO1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Distal myopathies v4.3 SMPX Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: SMPX.
Tag Q3_23_MOI was removed from gene: SMPX.
Distal myopathies v4.3 SMPX Eleanor Williams reviewed gene: SMPX: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Distal myopathies v4.2 SMPX Achchuthan Shanmugasundram Source Expert Review Green was added to SMPX.
Source NHS GMS was added to SMPX.
Mode of inheritance for gene SMPX 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)
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary ataxia with onset in adulthood v5.3 UCHL1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: UCHL1.
Tag Q3_23_MOI was removed from gene: UCHL1.
Hereditary ataxia with onset in adulthood v5.3 TDP1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: TDP1.
Hereditary ataxia with onset in adulthood v5.3 UCHL1 Eleanor Williams reviewed gene: UCHL1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary ataxia with onset in adulthood v5.3 TDP1 Eleanor Williams reviewed gene: TDP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary ataxia with onset in adulthood v5.2 UCHL1 Achchuthan Shanmugasundram Source Expert Review Green was added to UCHL1.
Mode of inheritance for gene UCHL1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary ataxia with onset in adulthood v5.2 TDP1 Achchuthan Shanmugasundram Source Expert Review Green was added to TDP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v5.3 ZC4H2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: ZC4H2.
Clefting v5.3 TRRAP Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: TRRAP.
Clefting v5.3 STAG2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: STAG2.
Clefting v5.3 SMARCA4 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: SMARCA4.
Clefting v5.3 PGM1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PGM1.
Clefting v5.3 PGAP3 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PGAP3.
Clefting v5.3 KAT6B Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: KAT6B.
Clefting v5.3 HNRNPK Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: HNRNPK.
Clefting v5.3 GLI2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: GLI2.
Clefting v5.3 CNTNAP1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: CNTNAP1.
Clefting v5.3 AMOTL1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: AMOTL1.
Clefting v5.3 ALX1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: ALX1.
Clefting v5.3 ZC4H2 Sarah Leigh reviewed gene: ZC4H2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Clefting v5.3 TRRAP Sarah Leigh reviewed gene: TRRAP: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Clefting v5.3 STAG2 Sarah Leigh reviewed gene: STAG2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Clefting v5.3 SMARCA4 Sarah Leigh reviewed gene: SMARCA4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Clefting v5.3 PGM1 Sarah Leigh reviewed gene: PGM1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Clefting v5.3 PGAP3 Sarah Leigh reviewed gene: PGAP3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Clefting v5.3 KAT6B Sarah Leigh reviewed gene: KAT6B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Clefting v5.3 HNRNPK Sarah Leigh reviewed gene: HNRNPK: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Clefting v5.3 GLI2 Sarah Leigh reviewed gene: GLI2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Clefting v5.3 CNTNAP1 Sarah Leigh reviewed gene: CNTNAP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Clefting v5.3 AMOTL1 Sarah Leigh reviewed gene: AMOTL1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Clefting v5.3 ALX1 Sarah Leigh edited their review of gene: ALX1: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Clefting v5.2 ZC4H2 Achchuthan Shanmugasundram Source Expert Review Green was added to ZC4H2.
Source NHS GMS was added to ZC4H2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v5.2 TRRAP Achchuthan Shanmugasundram Source Expert Review Green was added to TRRAP.
Source NHS GMS was added to TRRAP.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v5.2 STAG2 Achchuthan Shanmugasundram Source Expert Review Green was added to STAG2.
Source NHS GMS was added to STAG2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v5.2 SMARCA4 Achchuthan Shanmugasundram Source Expert Review Green was added to SMARCA4.
Source NHS GMS was added to SMARCA4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v5.2 PGM1 Achchuthan Shanmugasundram Source Expert Review Green was added to PGM1.
Source NHS GMS was added to PGM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v5.2 PGAP3 Achchuthan Shanmugasundram Source Expert Review Green was added to PGAP3.
Source NHS GMS was added to PGAP3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v5.2 KAT6B Achchuthan Shanmugasundram Source Expert Review Green was added to KAT6B.
Source NHS GMS was added to KAT6B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v5.2 HNRNPK Achchuthan Shanmugasundram Source Expert Review Green was added to HNRNPK.
Source NHS GMS was added to HNRNPK.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v5.2 GLI2 Achchuthan Shanmugasundram Source Expert Review Green was added to GLI2.
Source NHS GMS was added to GLI2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v5.2 CNTNAP1 Achchuthan Shanmugasundram Source Expert Review Green was added to CNTNAP1.
Source NHS GMS was added to CNTNAP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v5.2 AMOTL1 Achchuthan Shanmugasundram Source Expert Review Green was added to AMOTL1.
Source NHS GMS was added to AMOTL1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v5.2 ALX1 Achchuthan Shanmugasundram Source Expert Review Green was added to ALX1.
Source NHS GMS was added to ALX1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v5.3 THG1L Achchuthan Shanmugasundram Tag watchlist was removed from gene: THG1L.
Tag Q4_23_promote_green was removed from gene: THG1L.
Tag Q4_23_NHS_review was removed from gene: THG1L.
Ataxia and cerebellar anomalies - narrow panel v5.3 DLG4 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: DLG4.
Ataxia and cerebellar anomalies - narrow panel v5.3 ASL Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ASL.
Tag Q4_23_NHS_review was removed from gene: ASL.
Ataxia and cerebellar anomalies - narrow panel v5.3 UCHL1 Achchuthan Shanmugasundram Tag Q3_23_MOI was removed from gene: UCHL1.
Ataxia and cerebellar anomalies - narrow panel v5.3 LETM1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: LETM1.
Tag Q3_23_MOI was removed from gene: LETM1.
Ataxia and cerebellar anomalies - narrow panel v5.3 DNAJC3 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: DNAJC3.
Ataxia and cerebellar anomalies - narrow panel v5.3 DAGLA Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: DAGLA.
Ataxia and cerebellar anomalies - narrow panel v5.3 AGTPBP1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: AGTPBP1.
Ataxia and cerebellar anomalies - narrow panel v5.3 UCHL1 Sarah Leigh commented on gene: UCHL1: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Ataxia and cerebellar anomalies - narrow panel v5.3 THG1L Sarah Leigh reviewed gene: THG1L: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v5.3 LETM1 Sarah Leigh commented on gene: LETM1: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Ataxia and cerebellar anomalies - narrow panel v5.3 DNAJC3 Sarah Leigh reviewed gene: DNAJC3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v5.3 DLG4 Sarah Leigh reviewed gene: DLG4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia and cerebellar anomalies - narrow panel v5.3 DAGLA Sarah Leigh reviewed gene: DAGLA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia and cerebellar anomalies - narrow panel v5.3 ASL Sarah Leigh reviewed gene: ASL: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v5.3 AGTPBP1 Sarah Leigh reviewed gene: AGTPBP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v5.2 UCHL1 Achchuthan Shanmugasundram Mode of inheritance for gene UCHL1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v5.2 THG1L Achchuthan Shanmugasundram Source Expert Review Green was added to THG1L.
Source NHS GMS was added to THG1L.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v5.2 LETM1 Achchuthan Shanmugasundram Source Expert Review Green was added to LETM1.
Source NHS GMS was added to LETM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v5.2 DNAJC3 Achchuthan Shanmugasundram Source Expert Review Green was added to DNAJC3.
Source NHS GMS was added to DNAJC3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v5.2 DLG4 Achchuthan Shanmugasundram Source Expert Review Green was added to DLG4.
Source NHS GMS was added to DLG4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v5.2 DAGLA Achchuthan Shanmugasundram Source Expert Review Green was added to DAGLA.
Source NHS GMS was added to DAGLA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v5.2 ASL Achchuthan Shanmugasundram Source Expert Review Green was added to ASL.
Source NHS GMS was added to ASL.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v5.2 AGTPBP1 Achchuthan Shanmugasundram Source Expert Review Green was added to AGTPBP1.
Source NHS GMS was added to AGTPBP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rhabdomyolysis and metabolic muscle disorders v4.4 TAMM41 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: TAMM41.
Rhabdomyolysis and metabolic muscle disorders v4.4 PNPLA2 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: PNPLA2.
Rhabdomyolysis and metabolic muscle disorders v4.4 ISCU Arina Puzriakova Phenotypes for gene: ISCU were changed from Myopathy with lactic acidosis, hereditary 255125 to Myopathy with lactic acidosis, hereditary, OMIM:255125
Rhabdomyolysis and metabolic muscle disorders v4.3 ISCU Arina Puzriakova Tag for-review was removed from gene: ISCU.
Tag to_be_confirmed_NHSE was removed from gene: ISCU.
Rhabdomyolysis and metabolic muscle disorders v4.3 ABHD5 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: ABHD5.
Rhabdomyolysis and metabolic muscle disorders v4.3 ABHD5 Arina Puzriakova edited their review of gene: ABHD5: Changed rating: GREEN
Rhabdomyolysis and metabolic muscle disorders v4.3 ABHD5 Arina Puzriakova changed review comment from: The mode of inheritance of this gene has been updated to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to Green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Mitochondrial disorders v6.4 ANO10 Achchuthan Shanmugasundram Tag Q3_23_expert_review was removed from gene: ANO10.
Tag Q2_24_demote_amber tag was added to gene: ANO10.
Tag Q2_24_expert_review tag was added to gene: ANO10.
Mitochondrial disorders v6.4 BTD Achchuthan Shanmugasundram Tag Q3_23_expert_review was removed from gene: BTD.
Tag Q2_24_demote_amber tag was added to gene: BTD.
Tag Q2_24_expert_review tag was added to gene: BTD.
Rhabdomyolysis and metabolic muscle disorders v4.3 ISCU Arina Puzriakova edited their review of gene: ISCU: Added comment: The mode of inheritance of this gene has been updated to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rhabdomyolysis and metabolic muscle disorders v4.3 TAMM41 Arina Puzriakova reviewed gene: TAMM41: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rhabdomyolysis and metabolic muscle disorders v4.3 PNPLA2 Arina Puzriakova reviewed gene: PNPLA2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rhabdomyolysis and metabolic muscle disorders v4.3 ABHD5 Arina Puzriakova reviewed gene: ABHD5: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rhabdomyolysis and metabolic muscle disorders v4.2 TAMM41 Arina Puzriakova Source Expert Review Green was added to TAMM41.
Source NHS GMS was added to TAMM41.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rhabdomyolysis and metabolic muscle disorders v4.2 PNPLA2 Arina Puzriakova Source Expert Review Green was added to PNPLA2.
Source NHS GMS was added to PNPLA2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rhabdomyolysis and metabolic muscle disorders v4.2 ISCU Arina Puzriakova Source NHS GMS was added to ISCU.
Mode of inheritance for gene ISCU was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Rhabdomyolysis and metabolic muscle disorders v4.2 ABHD5 Arina Puzriakova Source Expert Review Green was added to ABHD5.
Source NHS GMS was added to ABHD5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v5.4 HECTD4 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: HECTD4.
Malformations of cortical development v5.4 COL4A2 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: COL4A2.
Tag Q4_23_NHS_review was removed from gene: COL4A2.
Intellectual disability v6.7 CASP2 Arina Puzriakova Phenotypes for gene: CASP2 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly, OMIM:620653
DDG2P v4.3 CASP2 Arina Puzriakova Phenotypes for gene: CASP2 were changed from AUTOSOMAL RECESSIVE MENTAL RETARDATION to Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly, OMIM:620653
Malformations of cortical development v5.4 COL4A1 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: COL4A1.
Tag Q4_23_NHS_review was removed from gene: COL4A1.
Malformations of cortical development v5.4 CASP2 Arina Puzriakova Phenotypes for gene: CASP2 were changed from neurodevelopmental disorder, MONDO:0700092; hereditary cerebral malformation, MONDO:0957008 to Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly, OMIM:620653
Malformations of cortical development v5.3 CASP2 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: CASP2.
Malformations of cortical development v5.3 HECTD4 Arina Puzriakova Source Expert Review Green was added to HECTD4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v5.3 COL4A2 Arina Puzriakova Source NHS GMS was added to COL4A2.
Source Expert Review Green was added to COL4A2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v5.3 COL4A1 Arina Puzriakova Source NHS GMS was added to COL4A1.
Source Expert Review Green was added to COL4A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v5.3 CASP2 Arina Puzriakova Source NHS GMS was added to CASP2.
Source Expert Review Green was added to CASP2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v5.2 HECTD4 Arina Puzriakova commented on gene: HECTD4: The rating of this gene has been updated to Green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Malformations of cortical development v5.2 COL4A2 Arina Puzriakova reviewed gene: COL4A2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Malformations of cortical development v5.2 COL4A1 Arina Puzriakova reviewed gene: COL4A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Malformations of cortical development v5.2 CASP2 Arina Puzriakova reviewed gene: CASP2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.4 HPDL Achchuthan Shanmugasundram Tag for-review was removed from gene: HPDL.
Tag to_be_confirmed_NHSE was removed from gene: HPDL.
Mitochondrial disorders v6.4 PTCD3 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: PTCD3.
Mitochondrial disorders v6.4 TEFM Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: TEFM.
Tag Q4_23_NHS_review was removed from gene: TEFM.
Mitochondrial disorders v6.4 TAMM41 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: TAMM41.
Tag Q4_23_NHS_review was removed from gene: TAMM41.
Mitochondrial disorders v6.4 SLC52A3 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SLC52A3.
Tag Q4_23_MOI was removed from gene: SLC52A3.
Mitochondrial disorders v6.4 SLC52A2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SLC52A2.
Mitochondrial disorders v6.4 SLC25A36 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SLC25A36.
Tag Q4_23_NHS_review was removed from gene: SLC25A36.
Mitochondrial disorders v6.4 MRM2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: MRM2.
Mitochondrial disorders v6.4 HADHB Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: HADHB.
Mitochondrial disorders v6.4 COX5A Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: COX5A.
Mitochondrial disorders v6.4 COX11 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: COX11.
Mitochondrial disorders v6.4 ATP5E Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ATP5E.
Mitochondrial disorders v6.4 SLC25A24 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: SLC25A24.
Mitochondrial disorders v6.4 SLC25A20 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: SLC25A20.
Mitochondrial disorders v6.4 SLC22A5 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: SLC22A5.
Mitochondrial disorders v6.4 QARS Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: QARS.
Mitochondrial disorders v6.4 PPOX Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PPOX.
Mitochondrial disorders v6.4 PLA2G6 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PLA2G6.
Mitochondrial disorders v6.4 PITRM1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PITRM1.
Mitochondrial disorders v6.4 PANK2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PANK2.
Mitochondrial disorders v6.4 OXCT1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: OXCT1.
Hydrocephalus v4.6 HYLS1 Arina Puzriakova Tag to_be_confirmed_NHSE was removed from gene: HYLS1.
Hydrocephalus v4.6 MYMK Arina Puzriakova Tag to_be_confirmed_NHSE was removed from gene: MYMK.
Hydrocephalus v4.6 ERF Arina Puzriakova Tag to_be_confirmed_NHSE was removed from gene: ERF.
Hydrocephalus v4.6 MYMK Arina Puzriakova reviewed gene: MYMK: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hydrocephalus v4.6 HYLS1 Arina Puzriakova reviewed gene: HYLS1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hydrocephalus v4.6 ERF Arina Puzriakova reviewed gene: ERF: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hydrocephalus v4.5 MYMK Arina Puzriakova Source Expert Review Amber was added to MYMK.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Hydrocephalus v4.5 ERF Arina Puzriakova Source Expert Review Red was added to ERF.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Mitochondrial disorders v6.4 TEFM Sarah Leigh edited their review of gene: TEFM: Changed rating: GREEN
Mitochondrial disorders v6.4 TAMM41 Sarah Leigh edited their review of gene: TAMM41: Changed rating: GREEN
Mitochondrial disorders v6.4 SLC25A36 Sarah Leigh edited their review of gene: SLC25A36: Changed rating: GREEN
Mitochondrial disorders v6.4 QARS Sarah Leigh edited their review of gene: QARS: Changed rating: GREEN
Mitochondrial disorders v6.4 PPOX Sarah Leigh edited their review of gene: PPOX: Changed rating: GREEN
Mitochondrial disorders v6.4 PANK2 Sarah Leigh edited their review of gene: PANK2: Changed rating: GREEN
Mitochondrial disorders v6.4 OXCT1 Sarah Leigh edited their review of gene: OXCT1: Changed rating: GREEN
Mitochondrial disorders v6.4 HADHB Sarah Leigh edited their review of gene: HADHB: Changed rating: GREEN
Holoprosencephaly - NOT chromosomal v4.9 DISP1 Arina Puzriakova Tag to_be_confirmed_NHSE was removed from gene: DISP1.
Holoprosencephaly - NOT chromosomal v4.9 DISP1 Arina Puzriakova changed review comment from: The rating of this gene has been updated to Amber following NHS Genomic Medicine Service approval.; to: The rating of this gene has been demoted to Amber following NHS Genomic Medicine Service approval.
Holoprosencephaly - NOT chromosomal v4.9 DISP1 Arina Puzriakova reviewed gene: DISP1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Holoprosencephaly - NOT chromosomal v4.8 DISP1 Arina Puzriakova Source Expert Review Amber was added to DISP1.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Mitochondrial disorders v6.3 TEFM Sarah Leigh reviewed gene: TEFM: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 TAMM41 Sarah Leigh reviewed gene: TAMM41: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 SLC52A3 Sarah Leigh commented on gene: SLC52A3: The rating of this gene has been updated to green and the mode of inheritance updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Mitochondrial disorders v6.3 SLC52A2 Sarah Leigh edited their review of gene: SLC52A2: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 SLC25A36 Sarah Leigh reviewed gene: SLC25A36: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 SLC25A24 Sarah Leigh commented on gene: SLC25A24: The rating of this gene has been updated to green and the mode of inheritance updated to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Mitochondrial disorders v6.3 SLC25A20 Sarah Leigh edited their review of gene: SLC25A20: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 SLC22A5 Sarah Leigh commented on gene: SLC22A5: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Mitochondrial disorders v6.3 QARS Sarah Leigh reviewed gene: QARS: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 PTCD3 Sarah Leigh edited their review of gene: PTCD3: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 PPOX Sarah Leigh edited their review of gene: PPOX: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 PLA2G6 Sarah Leigh commented on gene: PLA2G6: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Mitochondrial disorders v6.3 PITRM1 Sarah Leigh edited their review of gene: PITRM1: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 PANK2 Sarah Leigh reviewed gene: PANK2: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 OXCT1 Sarah Leigh edited their review of gene: OXCT1: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 MRM2 Sarah Leigh edited their review of gene: MRM2: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 HPDL Sarah Leigh edited their review of gene: HPDL: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 HADHB Sarah Leigh edited their review of gene: HADHB: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 COX5A Sarah Leigh edited their review of gene: COX5A: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 COX11 Sarah Leigh edited their review of gene: COX11: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 ATP5E Sarah Leigh edited their review of gene: ATP5E: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.2 TEFM Achchuthan Shanmugasundram Source NHS GMS was added to TEFM.
Source Expert Review Green was added to TEFM.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 TAMM41 Achchuthan Shanmugasundram Source NHS GMS was added to TAMM41.
Source Expert Review Green was added to TAMM41.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 SLC52A3 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC52A3.
Mode of inheritance for gene SLC52A3 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 SLC52A2 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC52A2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 SLC25A36 Achchuthan Shanmugasundram Source NHS GMS was added to SLC25A36.
Source Expert Review Green was added to SLC25A36.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 SLC25A24 Achchuthan Shanmugasundram Source NHS GMS was added to SLC25A24.
Source Expert Review Green was added to SLC25A24.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 SLC25A20 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC25A20.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 SLC22A5 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC22A5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 QARS Achchuthan Shanmugasundram Source NHS GMS was added to QARS.
Source Expert Review Green was added to QARS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 PTCD3 Achchuthan Shanmugasundram Source Expert Review Green was added to PTCD3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 PPOX Achchuthan Shanmugasundram Source Expert Review Green was added to PPOX.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 PLA2G6 Achchuthan Shanmugasundram Source NHS GMS was added to PLA2G6.
Source Expert Review Green was added to PLA2G6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 PITRM1 Achchuthan Shanmugasundram Source NHS GMS was added to PITRM1.
Source Expert Review Green was added to PITRM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 PANK2 Achchuthan Shanmugasundram Source NHS GMS was added to PANK2.
Source Expert Review Green was added to PANK2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 OXCT1 Achchuthan Shanmugasundram Source Expert Review Green was added to OXCT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 MRM2 Achchuthan Shanmugasundram Source Expert Review Green was added to MRM2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 HPDL Achchuthan Shanmugasundram Source NHS GMS was added to HPDL.
Source Expert Review Green was added to HPDL.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 HADHB Achchuthan Shanmugasundram Source Expert Review Green was added to HADHB.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 COX5A Achchuthan Shanmugasundram Source NHS GMS was added to COX5A.
Source Expert Review Green was added to COX5A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 COX11 Achchuthan Shanmugasundram Source Expert Review Green was added to COX11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 ATP5E Achchuthan Shanmugasundram Source NHS GMS was added to ATP5E.
Source Expert Review Green was added to ATP5E.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.6 SPTBN4 Arina Puzriakova Phenotypes for gene: SPTBN4 were changed from Neurodevelopmental disorder with hypotonia, neuropathy, and deafness MIM#617519 to Neurodevelopmental disorder with hypotonia, neuropathy, and deafness, OMIM:617519
Early onset or syndromic epilepsy v5.4 SPTBN4 Arina Puzriakova Phenotypes for gene: SPTBN4 were changed from Neurodevelopmental disorder with hypotonia, neuropathy, and deafness MIM#617519 to Neurodevelopmental disorder with hypotonia, neuropathy, and deafness, OMIM:617519
Monogenic hearing loss v4.41 SPTBN4 Arina Puzriakova Phenotypes for gene: SPTBN4 were changed from Neurodevelopmental disorder with hypotonia, neuropathy, and deafness, 617519 to Neurodevelopmental disorder with hypotonia, neuropathy, and deafness, OMIM:617519
DDG2P v4.2 SPTBN4 Arina Puzriakova Phenotypes for gene: SPTBN4 were changed from NEURODEVELOPMENTAL DISORDER WITH HYPOTONIA, NEUROPATHY, AND DEAFNESS, OMIM:617519 to Neurodevelopmental disorder with hypotonia, neuropathy, and deafness, OMIM:617519
Hereditary neuropathy v1.478 SPTBN4 Arina Puzriakova Phenotypes for gene: SPTBN4 were changed from Neurodevelopmental disorder with hypotonia, neuropathy, and deafness, 617519 to Neurodevelopmental disorder with hypotonia, neuropathy, and deafness, OMIM:617519
Hereditary neuropathy or pain disorder v4.8 SPTBN4 Arina Puzriakova Phenotypes for gene: SPTBN4 were changed from Neurodevelopmental disorder with hypotonia, neuropathy, and deafness, 617519 to Neurodevelopmental disorder with hypotonia, neuropathy, and deafness, OMIM:617519
Hereditary neuropathy or pain disorder v4.7 SPTBN4 Arina Puzriakova Tag for-review was removed from gene: SPTBN4.
Tag to_be_confirmed_NHSE was removed from gene: SPTBN4.
Hereditary neuropathy or pain disorder v4.7 NEMF Arina Puzriakova Phenotypes for gene: NEMF were changed from Hypotonia; Axonal neuropathy; Ataxia; Abnormal brain imaging; Global developmental delay; Intellectual disability; Kyphosis; Scoliosis; Tremor; Respiratory distress to Intellectual developmental disorder with speech delay and axonal peripheral neuropathy, OMIM:619099
Hereditary neuropathy or pain disorder v4.6 NEMF Arina Puzriakova Tag watchlist was removed from gene: NEMF.
Tag for-review was removed from gene: NEMF.
Tag to_be_confirmed_NHSE was removed from gene: NEMF.
Hereditary neuropathy or pain disorder v4.6 SYT2 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: SYT2.
Hereditary neuropathy or pain disorder v4.6 SPTAN1 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: SPTAN1.
Hereditary neuropathy or pain disorder v4.6 SARS Arina Puzriakova Tag Q4_23_promote_green was removed from gene: SARS.
Tag Q4_23_NHS_review was removed from gene: SARS.
Hereditary neuropathy or pain disorder v4.6 PPOX Arina Puzriakova Phenotypes for gene: PPOX were changed from Porphyria variegata, 176200; Skin photosensitivity. Acute episodes similar to AIP to Porphyria variegata, OMIM:176200; Sensory neuropathy, HP:0000763
Hereditary neuropathy or pain disorder v4.5 PPOX Arina Puzriakova Tag Q3_23_MOI was removed from gene: PPOX.
Hereditary neuropathy or pain disorder v4.5 ITPR3 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: ITPR3.
Hereditary neuropathy or pain disorder v4.5 DNAJC3 Arina Puzriakova Phenotypes for gene: DNAJC3 were changed from Cerebellar ataxia, neuropathy with SNCV, hearing loss, diabetes mellitus; Ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus, 616192 to Ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus, OMIM:616192
Hereditary neuropathy or pain disorder v4.4 DNAJC3 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: DNAJC3.
Hereditary neuropathy or pain disorder v4.4 DHX9 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: DHX9.
Hereditary neuropathy or pain disorder v4.4 DHTKD1 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: DHTKD1.
Hereditary neuropathy or pain disorder v4.4 AGTPBP1 Arina Puzriakova Phenotypes for gene: AGTPBP1 were changed from Early onset cerebellar atrophy, developmental delay, and feeding and respiratory difficulties, severe motor neuronopathy; Neurodegeneration, childhood-onset, with cerebellar atrophy, 618276 to Neurodegeneration, childhood-onset, with cerebellar atrophy, OMIM:618276
Hereditary neuropathy or pain disorder v4.3 AGTPBP1 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: AGTPBP1.
Hereditary neuropathy or pain disorder v4.3 SPTBN4 Arina Puzriakova edited their review of gene: SPTBN4: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Hereditary neuropathy or pain disorder v4.3 NEMF Arina Puzriakova edited their review of gene: NEMF: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.3 SYT2 Arina Puzriakova reviewed gene: SYT2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v4.3 SPTAN1 Arina Puzriakova reviewed gene: SPTAN1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v4.3 SLC12A6 Arina Puzriakova edited their review of gene: SLC12A6: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.3 SARS Arina Puzriakova reviewed gene: SARS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v4.3 PPOX Arina Puzriakova reviewed gene: PPOX: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.3 ITPR3 Arina Puzriakova reviewed gene: ITPR3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v4.3 DNAJC3 Arina Puzriakova reviewed gene: DNAJC3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.3 DHX9 Arina Puzriakova edited their review of gene: DHX9: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v4.3 DHTKD1 Arina Puzriakova reviewed gene: DHTKD1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v4.3 AGTPBP1 Arina Puzriakova reviewed gene: AGTPBP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.2 SYT2 Arina Puzriakova Source Expert Review Green was added to SYT2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v4.2 SPTBN4 Arina Puzriakova Source NHS GMS was added to SPTBN4.
Source Expert Review Green was added to SPTBN4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v4.2 SPTAN1 Arina Puzriakova Source NHS GMS was added to SPTAN1.
Source Expert Review Green was added to SPTAN1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v4.2 SLC12A6 Arina Puzriakova Source Expert Review Green was added to SLC12A6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v4.2 SARS Arina Puzriakova Source NHS GMS was added to SARS.
Source Expert Review Green was added to SARS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v4.2 PPOX Arina Puzriakova Mode of inheritance for gene PPOX was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.2 NEMF Arina Puzriakova Source NHS GMS was added to NEMF.
Source Expert Review Green was added to NEMF.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v4.2 ITPR3 Arina Puzriakova Source NHS GMS was added to ITPR3.
Source Expert Review Green was added to ITPR3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v4.2 DNAJC3 Arina Puzriakova Source Expert Review Green was added to DNAJC3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v4.2 DHX9 Arina Puzriakova Source NHS GMS was added to DHX9.
Source Expert Review Green was added to DHX9.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v4.2 DHTKD1 Arina Puzriakova Source Expert Review Green was added to DHTKD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v4.2 AGTPBP1 Arina Puzriakova Source Expert Review Green was added to AGTPBP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Limb disorders v5.2 ISCA-37467-Gain Arina Puzriakova edited their review of Region: ISCA-37467-Gain: Added comment: The rating of this region has been updated to Green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown' following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v6.5 ISCA-46292-Loss Arina Puzriakova reviewed Region: ISCA-46292-Loss: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Severe microcephaly v5.3 ISCA-46743-Loss Arina Puzriakova reviewed Region: ISCA-46743-Loss: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v6.5 ISCA-46743-Loss Arina Puzriakova changed review comment from: The rating of this region has been updated to Green and the mode of inheritance set to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' following NHS Genomic Medicine Service approval. Evidence: multiple unrelated cases curated in ClinGen plus several others - sufficient evidence for this region. Phenotype: syndromic intellectual disability (congenital anomalies, behavioural problems and facial dysmorphism), seizures in about 30%. Modulated phenotype in females is reported.; to: The rating of this region has been updated to Green and the mode of inheritance set to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' following NHS Genomic Medicine Service approval. Evidence: two cases (PMID: 30158690; 33758131) with intragenic STAG2 deletions but listed as sufficient evidence in ClinGen. Region encompasses STAG2 and some of XIAP. Phenotype: holoprosencephaly and/or developmental delay/ID based on LOF of STAG2 gene. Affected females are reported.
Early onset or syndromic epilepsy v5.3 ISCA-46743-Gain Arina Puzriakova changed review comment from: The rating of this region has been updated to Green and the mode of inheritance set to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' following NHS Genomic Medicine Service approval. Evidence: multiple unrelated cases curated in ClinGen plus several others - sufficient evidence for this region. Phenotype: syndromic intellectual disability (congenital anomalies, behavioural problems and facial dysmorphism). Modulated phenotype in females is reported.; to: The rating of this region has been updated to Green and the mode of inheritance set to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' following NHS Genomic Medicine Service approval. Evidence: multiple unrelated cases curated in ClinGen plus several others - sufficient evidence for this region. Phenotype: syndromic intellectual disability (congenital anomalies, behavioural problems and facial dysmorphism), seizures in about 30%. Modulated phenotype in females is reported.
Intellectual disability v6.5 ISCA-46743-Gain Arina Puzriakova reviewed Region: ISCA-46743-Gain: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Holoprosencephaly - NOT chromosomal v4.7 ISCA-46743-Loss Arina Puzriakova reviewed Region: ISCA-46743-Loss: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v6.5 ISCA-46743-Loss Arina Puzriakova reviewed Region: ISCA-46743-Loss: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Early onset or syndromic epilepsy v5.3 ISCA-46743-Gain Arina Puzriakova reviewed Region: ISCA-46743-Gain: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v6.5 ISCA-46292-Loss Arina Puzriakova Publications for Region: ISCA-46292-Loss were set to
Limb disorders v5.2 ISCA-37467-Gain Arina Puzriakova Tag Q3_23_promote_green was removed from Region: ISCA-37467-Gain.
Intellectual disability v6.4 ISCA-46743-Loss Arina Puzriakova Publications for Region: ISCA-46743-Loss were set to
Severe microcephaly v5.3 ISCA-46743-Loss Arina Puzriakova Publications for Region: ISCA-46743-Loss were set to
Holoprosencephaly - NOT chromosomal v4.7 ISCA-46743-Loss Arina Puzriakova Publications for Region: ISCA-46743-Loss were set to
Early onset or syndromic epilepsy v5.3 ISCA-46743-Gain Arina Puzriakova Publications for Region: ISCA-46743-Gain were set to
Intellectual disability v6.3 ISCA-46743-Gain Arina Puzriakova Publications for Region: ISCA-46743-Gain were set to
Limb disorders v5.2 ISCA-37467-Gain Arina Puzriakova Haploinsufficiency Score for ISCA-37467-Gain was changed from None to .
Source Expert Review Green was added to Region: ISCA-37467-Gain.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.2 ISCA-46292-Loss Arina Puzriakova Region: ISCA-46292-Loss was added
Region: ISCA-46292-Loss was added to Intellectual disability. Sources: Expert Review Green,ClinGen
Mode of inheritance for Region: ISCA-46292-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Severe microcephaly v5.2 ISCA-46743-Loss Arina Puzriakova Region: ISCA-46743-Loss was added
Region: ISCA-46743-Loss was added to Severe microcephaly. Sources: ClinGen,Expert Review Amber
Mode of inheritance for Region: ISCA-46743-Loss was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Holoprosencephaly - NOT chromosomal v4.6 ISCA-46743-Loss Arina Puzriakova Region: ISCA-46743-Loss was added
Region: ISCA-46743-Loss was added to Holoprosencephaly - NOT chromosomal. Sources: Expert Review Green,ClinGen
Mode of inheritance for Region: ISCA-46743-Loss was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v6.2 ISCA-46743-Loss Arina Puzriakova Region: ISCA-46743-Loss was added
Region: ISCA-46743-Loss was added to Intellectual disability. Sources: Expert Review Green,ClinGen
Mode of inheritance for Region: ISCA-46743-Loss was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Early onset or syndromic epilepsy v5.2 ISCA-46743-Gain Arina Puzriakova Region: ISCA-46743-Gain was added
Region: ISCA-46743-Gain was added to Early onset or syndromic epilepsy. Sources: Expert Review Green,ClinGen
Mode of inheritance for Region: ISCA-46743-Gain was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v6.2 ISCA-46743-Gain Arina Puzriakova Region: ISCA-46743-Gain was added
Region: ISCA-46743-Gain was added to Intellectual disability. Sources: Expert Review Green,ClinGen
Mode of inheritance for Region: ISCA-46743-Gain was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Rare multisystem ciliopathy Super panel v15.3 Arina Puzriakova Panel version 15.2 has been signed off on 2024-05-01
Hypotonic infant v29.2 Arina Puzriakova Panel version 29.1 has been signed off on 2024-05-01
Cystic renal disease v8.4 Eleanor Williams Panel version 8.3 has been signed off on 2024-05-01
Hereditary ataxia and cerebellar anomalies - childhood onset v15.3 Eleanor Williams Panel version 15.2 has been signed off on 2024-05-01
Sudden unexplained death or survivors of a cardiac event v19.74 Arina Puzriakova Panel version 19.73 has been signed off on 2024-05-01
Childhood onset leukodystrophy v19.3 Eleanor Williams Panel version 19.2 has been signed off on 2024-05-01
Unexplained death in infancy and sudden unexplained death in childhood v9.8 Arina Puzriakova Panel version 9.7 has been signed off on 2024-05-01
Cerebral malformation v11.3 Eleanor Williams Panel version 11.2 has been signed off on 2024-05-01
Other rare neuromuscular disorders v21.3 Eleanor Williams Panel version 21.2 has been signed off on 2024-05-01
Paediatric disorders v45.3 Arina Puzriakova Panel version 45.2 has been signed off on 2024-05-01
Short QT syndrome v3.12 Achchuthan Shanmugasundram Panel version 3.11 has been signed off on 2024-05-01
Progressive cardiac conduction disease v2.8 Achchuthan Shanmugasundram Panel version 2.7 has been signed off on 2024-05-01
Catecholaminergic polymorphic VT v4.6 Achchuthan Shanmugasundram Panel version 4.5 has been signed off on 2024-05-01
Hypertrophic cardiomyopathy v4.9 Achchuthan Shanmugasundram Panel version 4.8 has been signed off on 2024-05-01
Autoinflammatory disorders v2.1 Eleanor Williams Panel version 2.0 has been signed off on 2024-05-01
Autoinflammatory disorders v2.0 Eleanor Williams promoted panel to version 2.0
Brugada syndrome and cardiac sodium channel disease v3.10 Achchuthan Shanmugasundram Panel version 3.9 has been signed off on 2024-05-01
Unexplained young onset end-stage renal disease v4.1 Eleanor Williams Panel version 4.0 has been signed off on 2024-05-01
Differences in sex development v4.6 Achchuthan Shanmugasundram Panel version 4.5 has been signed off on 2024-05-01
Unexplained young onset end-stage renal disease v4.0 Eleanor Williams promoted panel to version 4.0
Arrhythmogenic right ventricular cardiomyopathy v3.11 Achchuthan Shanmugasundram Panel version 3.10 has been signed off on 2024-05-01
Cystic kidney disease v5.1 Eleanor Williams Panel version 5.0 has been signed off on 2024-05-01
Cystic kidney disease v5.0 Eleanor Williams promoted panel to version 5.0
Arthrogryposis v6.1 Achchuthan Shanmugasundram Panel version 6.0 has been signed off on 2024-05-01
Arthrogryposis v6.0 Achchuthan Shanmugasundram promoted panel to version 6.0
Retinal disorders v5.1 Eleanor Williams Panel version 5.0 has been signed off on 2024-05-01
Retinal disorders v5.0 Eleanor Williams promoted panel to version 5.0
Distal myopathies v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2024-05-01
Distal myopathies v4.0 Arina Puzriakova promoted panel to version 4.0
Severe microcephaly v5.1 Achchuthan Shanmugasundram Panel version 5.0 has been signed off on 2024-05-01
Malformations of cortical development v5.1 Arina Puzriakova Panel version 5.0 has been signed off on 2024-05-01
Malformations of cortical development v5.0 Arina Puzriakova promoted panel to version 5.0
Ophthalmological ciliopathies v4.1 Eleanor Williams Panel version 4.0 has been signed off on 2024-05-01
Rhabdomyolysis and metabolic muscle disorders v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2024-05-01
Severe microcephaly v5.0 Achchuthan Shanmugasundram promoted panel to version 5.0
Rhabdomyolysis and metabolic muscle disorders v4.0 Arina Puzriakova promoted panel to version 4.0
Neurological ciliopathies v4.1 Achchuthan Shanmugasundram Panel version 4.0 has been signed off on 2024-05-01
Rare syndromic craniosynostosis or isolated multisuture synostosis v5.1 Arina Puzriakova Panel version 5.0 has been signed off on 2024-05-01
Rare syndromic craniosynostosis or isolated multisuture synostosis v5.0 Arina Puzriakova promoted panel to version 5.0
Ophthalmological ciliopathies v4.0 Eleanor Williams promoted panel to version 4.0
Skeletal ciliopathies v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2024-05-01
Neurological ciliopathies v4.0 Achchuthan Shanmugasundram promoted panel to version 4.0
Neurological segmental overgrowth v2.13 Ivone Leong Panel version 2.12 has been signed off on 2024-05-01
Congenital myaesthenic syndrome v4.6 Ivone Leong Panel version 4.5 has been signed off on 2024-05-01
Ataxia and cerebellar anomalies - narrow panel v5.1 Achchuthan Shanmugasundram Panel version 5.0 has been signed off on 2024-05-01
Childhood onset dystonia, chorea or related movement disorder v4.1 Eleanor Williams Panel version 4.0 has been signed off on 2024-05-01
Ataxia and cerebellar anomalies - narrow panel v5.0 Achchuthan Shanmugasundram promoted panel to version 5.0
Skeletal ciliopathies v4.0 Arina Puzriakova promoted panel to version 4.0
Limb disorders v5.1 Arina Puzriakova Panel version 5.0 has been signed off on 2024-05-01
White matter disorders and cerebral calcification - narrow panel v4.1 Achchuthan Shanmugasundram Panel version 4.0 has been signed off on 2024-05-01
Congenital myopathy v4.38 Ivone Leong Panel version 4.37 has been signed off on 2024-05-01
Childhood onset dystonia, chorea or related movement disorder v4.0 Eleanor Williams promoted panel to version 4.0
White matter disorders and cerebral calcification - narrow panel v4.0 Achchuthan Shanmugasundram promoted panel to version 4.0
Congenital muscular dystrophy v4.24 Ivone Leong Panel version 4.23 has been signed off on 2024-05-01
DDG2P v4.1 Achchuthan Shanmugasundram Panel version 4.0 has been signed off on 2024-05-01
Hereditary neuropathy or pain disorder v4.1 Eleanor Williams Panel version 4.0 has been signed off on 2024-05-01
Limb disorders v5.0 Arina Puzriakova promoted panel to version 5.0
Hereditary neuropathy or pain disorder v4.0 Eleanor Williams promoted panel to version 4.0
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.33 Ivone Leong Panel version 4.32 has been signed off on 2024-05-01
DDG2P v4.0 Achchuthan Shanmugasundram promoted panel to version 4.0
Paediatric motor neuronopathies v3.7 Ivone Leong Panel version 3.6 has been signed off on 2024-05-01
Adult onset leukodystrophy v4.1 Eleanor Williams Panel version 4.0 has been signed off on 2024-05-01
Paediatric disorders - additional genes v4.1 Achchuthan Shanmugasundram Panel version 4.0 has been signed off on 2024-05-01
Adult onset leukodystrophy v4.0 Eleanor Williams promoted panel to version 4.0
Mitochondrial disorders v6.1 Arina Puzriakova Panel version 6.0 has been signed off on 2024-05-01
Familial hypoparathyroidism v2.15 Ivone Leong Panel version 2.14 has been signed off on 2024-05-01
Paediatric disorders - additional genes v4.0 Achchuthan Shanmugasundram promoted panel to version 4.0
Skeletal dysplasia v5.1 Arina Puzriakova Panel version 5.0 has been signed off on 2024-05-01
Skeletal dysplasia v5.0 Arina Puzriakova promoted panel to version 5.0
Possible mitochondrial disorder - nuclear genes v3.106 Ivone Leong Panel version 3.105 has been signed off on 2024-05-01
Clefting v5.1 Arina Puzriakova Panel version 5.0 has been signed off on 2024-05-01
Paediatric or syndromic cardiomyopathy v4.1 Achchuthan Shanmugasundram Panel version 4.0 has been signed off on 2024-05-01
Childhood onset hereditary spastic paraplegia v5.1 Eleanor Williams Panel version 5.0 has been signed off on 2024-05-01
Mitochondrial disorder with complex IV deficiency v3.21 Ivone Leong Panel version 3.20 has been signed off on 2024-05-01
Clefting v5.0 Arina Puzriakova promoted panel to version 5.0
Childhood onset hereditary spastic paraplegia v5.0 Eleanor Williams promoted panel to version 5.0
Respiratory ciliopathies including non-CF bronchiectasis v3.11 Ivone Leong Panel version 3.10 has been signed off on 2024-05-01
Adult onset hereditary spastic paraplegia v4.1 Eleanor Williams Panel version 4.0 has been signed off on 2024-05-01
Adult onset hereditary spastic paraplegia v4.0 Eleanor Williams promoted panel to version 4.0
Laterality disorders and isomerism v3.10 Ivone Leong Panel version 3.9 has been signed off on 2024-05-01
Mitochondrial disorders v6.0 Arina Puzriakova promoted panel to version 6.0
Paediatric or syndromic cardiomyopathy v4.0 Achchuthan Shanmugasundram promoted panel to version 4.0
Mitochondrial disorders v5.0 Arina Puzriakova promoted panel to version 5.0
Renal ciliopathies v3.6 Ivone Leong Panel version 3.5 has been signed off on 2024-05-01
Fetal anomalies v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2024-05-01
Early onset or syndromic epilepsy v5.1 Achchuthan Shanmugasundram Panel version 5.0 has been signed off on 2024-05-01
Fetal anomalies v4.0 Arina Puzriakova promoted panel to version 4.0
Holoprosencephaly - NOT chromosomal v4.5 Ivone Leong Panel version 4.4 has been signed off on 2024-05-01
Adult onset neurodegenerative disorder v5.1 Eleanor Williams Panel version 5.0 has been signed off on 2024-05-01
Adult onset neurodegenerative disorder v5.0 Eleanor Williams promoted panel to version 5.0
Early onset or syndromic epilepsy v5.0 Achchuthan Shanmugasundram promoted panel to version 5.0
Long QT syndrome v3.8 Ivone Leong Panel version 3.7 has been signed off on 2024-05-01
Hereditary ataxia with onset in adulthood v5.1 Eleanor Williams Panel version 5.0 has been signed off on 2024-05-01
Likely inborn error of metabolism v5.1 Arina Puzriakova Panel version 5.0 has been signed off on 2024-05-01
Primary immunodeficiency or monogenic inflammatory bowel disease v5.1 Arina Puzriakova Panel version 5.0 has been signed off on 2024-05-01
Dilated and arrhythmogenic cardiomyopathy v2.25 Ivone Leong Panel version 2.23 has been signed off on 2024-05-01
Hereditary ataxia with onset in adulthood v5.0 Eleanor Williams promoted panel to version 5.0
Primary immunodeficiency or monogenic inflammatory bowel disease v5.0 Arina Puzriakova promoted panel to version 5.0
Intellectual disability v6.1 Achchuthan Shanmugasundram Panel version 6.0 has been signed off on 2024-05-01
Monogenic hearing loss v4.40 Ivone Leong Panel version 4.39 has been signed off on 2024-05-01
Likely inborn error of metabolism v5.0 Arina Puzriakova promoted panel to version 5.0
Confirmed Fanconi anaemia or Bloom syndrome v2.6 Ivone Leong Panel version 2.5 has been signed off on 2024-05-01
Congenital disorders of glycosylation v5.1 Arina Puzriakova Panel version 5.0 has been signed off on 2024-05-01
Intellectual disability v6.0 Achchuthan Shanmugasundram promoted panel to version 6.0
Congenital disorders of glycosylation v5.0 Arina Puzriakova promoted panel to version 5.0
Dilated and arrhythmogenic cardiomyopathy v2.24 Ivone Leong Panel version 2.23 has been signed off on 2024-02-01
Paediatric disorders v35.1834 Achchuthan Shanmugasundram Changed child panels to: Intellectual disability; Early onset or syndromic epilepsy; Likely inborn error of metabolism - targeted testing not possible; Clefting; Skeletal dysplasia; Monogenic hearing loss; Limb disorders; DDG2P; Skeletal ciliopathies; Neurological ciliopathies; Paediatric disorders - additional genes; Ophthalmological ciliopathies; Renal ciliopathies
Unexplained death in infancy and sudden unexplained death in childhood v6.430 Eleanor Williams Changed child panels to: Early onset or syndromic epilepsy; Likely inborn error of metabolism - targeted testing not possible; Hypertrophic cardiomyopathy; Catecholaminergic polymorphic VT; Paediatric or syndromic cardiomyopathy; Short QT syndrome; Arrhythmogenic right ventricular cardiomyopathy; Brugada syndrome and cardiac sodium channel disease; Long QT syndrome; Dilated and arrhythmogenic cardiomyopathy; Progressive cardiac conduction disease
Confirmed Fanconi anaemia or Bloom syndrome v2.5 Ivone Leong List of related panels changed from R229; R258 to R229; R258; Confirmed Fanconi anaemia or Bloom syndrome - mutation testing; Cytopenia - Fanconi breakage testing indicated
Differences in sex development v4.5 Ivone Leong Panel name changed from Disorders of sex development to Differences in sex development
List of related panels changed from R146 to R146; Disorders of sex development
Intellectual disability v5.558 Arina Puzriakova Panel name changed from Intellectual disability - microarray and sequencing to Intellectual disability
List of related panels changed from Coarse facial features including Coffin-Siris-like disorders; ID; Moderate; severe or profound intellectual disability; Schizophrenia plus additional features; Intellectual disability - microarray; fragile X and sequencing; Intellectual disability; R29 to Coarse facial features including Coffin-Siris-like disorders; ID; Moderate; severe or profound intellectual disability; Schizophrenia plus additional features; Intellectual disability - microarray; fragile X and sequencing; Intellectual disability - microarray and sequencing; R29
Intellectual disability v5.557 DIP2B Dmitrijs Rots reviewed gene: DIP2B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v5.557 ADGRL1 Dmitrijs Rots gene: ADGRL1 was added
gene: ADGRL1 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: ADGRL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ADGRL1 were set to PubMed: 35907405
Phenotypes for gene: ADGRL1 were set to Developmental delay, behavioral abnormalities, and neuropsychiatric disorders
Review for gene: ADGRL1 was set to GREEN
Added comment: More than 10 cases described in PubMed: 35907405
Sources: Literature
Hypertrophic cardiomyopathy v4.7 SVIL Dmitrijs Rots gene: SVIL was added
gene: SVIL was added to Hypertrophic cardiomyopathy. Sources: Literature
Mode of inheritance for gene: SVIL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SVIL were set to PMID: 36778260
Phenotypes for gene: SVIL were set to HCM
Review for gene: SVIL was set to AMBER
Added comment: In the novel paper described:"the excess burden is even greater at 15.3-fold (95% CI: 5.7-41.3; P:7x10−7) when restricting the analysis to high confidence LoF variants affecting the predominant SVIL transcript in LV (ENST00000375400) (Supplementary Table 6b). In one family, the SVIL LoF variant (p.(Gln255*)) was carried by two cousins with HCM (parents deceased), providing some evidence of co-segregation. Taken together, these data support SVIL as a novel HCM disease gene."
Strong statistical evidence + one family segregating.
Sources: Literature
Familial non syndromic congenital heart disease v1.80 FLT4 Dmitrijs Rots edited their review of gene: FLT4: Added comment: Statistically proven 30582441 enrichment in multiple affected cases. Enough for green rating.; Changed phenotypes to: Congenital heart defect; Set current diagnostic: yes
Familial non syndromic congenital heart disease v1.80 FLT4 Dmitrijs Rots reviewed gene: FLT4: Rating: GREEN; Mode of pathogenicity: None; Publications: 30582441; Phenotypes: Congenital; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Thrombophilia with a likely monogenic cause v2.5 PLG Zornitza Stark reviewed gene: PLG: Rating: AMBER; Mode of pathogenicity: None; Publications: 35244080, 27976734; Phenotypes: Dysplasminogenemia, MIM# 217090; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Familial breast cancer v1.20 BARD1 Dmitrijs Rots edited their review of gene: BARD1: Added comment: PMID: 37592023 metaanlysis also reports significant association with breast cancer; Changed publications to: PMID: 37592023
Familial breast cancer v1.20 BARD1 Dmitrijs Rots reviewed gene: BARD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Arthrogryposis v5.31 SLC35A3 Hannah Knight reviewed gene: SLC35A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 28777481, 24031089, 28328131, 33416188; Phenotypes: Arthrogryposis, impaired intellectual development, and seizures, 615553 (3), Autosomal recessive; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.557 ZNFX1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: ZNFX1.
Early onset or syndromic epilepsy v4.196 ZNFX1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: ZNFX1.
Early onset or syndromic epilepsy v4.196 YIF1B Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: YIF1B.
Severe microcephaly v4.88 YIF1B Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: YIF1B.
Early onset or syndromic epilepsy v4.196 TRIT1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: TRIT1.
Ataxia and cerebellar anomalies - narrow panel v4.64 SVBP Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: SVBP.
Intellectual disability v5.557 RNPC3 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: RNPC3.
Mitochondrial disorders v4.169 PITRM1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: PITRM1.
Likely inborn error of metabolism v4.137 PITRM1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: PITRM1.
Intellectual disability v5.557 FILIP1 Achchuthan Shanmugasundram Tag gene-checked was removed from gene: FILIP1.
Arthrogryposis v5.31 FILIP1 Achchuthan Shanmugasundram Tag gene-checked was removed from gene: FILIP1.
Intellectual disability v5.557 OTUD7A Achchuthan Shanmugasundram Tag gene-checked was removed from gene: OTUD7A.
Early onset or syndromic epilepsy v4.196 OTUD7A Achchuthan Shanmugasundram Tag gene-checked was removed from gene: OTUD7A.
Hypertrophic cardiomyopathy v4.7 ALPK3 Dmitrijs Rots commented on gene: ALPK3: As described by Luis Lopes, should be BOTH monoallelic and biallelic on this panel.
Intellectual disability v5.557 CEP295 Achchuthan Shanmugasundram Phenotypes for gene: CEP295 were changed from Seckel syndrome 11, OMIM # 620767 to Seckel syndrome 11, OMIM:620767
Intellectual disability v5.556 CEP295 Achchuthan Shanmugasundram Classified gene: CEP295 as Amber List (moderate evidence)
Intellectual disability v5.556 CEP295 Achchuthan Shanmugasundram Gene: cep295 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.555 CEP295 Achchuthan Shanmugasundram reviewed gene: CEP295: Rating: AMBER; Mode of pathogenicity: None; Publications: 38154379; Phenotypes: Seckel syndrome 11, OMIM:620767; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.555 DOCK4 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: DOCK4.
Intellectual disability v5.555 DOCK4 Achchuthan Shanmugasundram Classified gene: DOCK4 as Amber List (moderate evidence)
Intellectual disability v5.555 DOCK4 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, PMID:38526744 reported seven unrelated individuals with heterozygous variants and with developmental delay or intellectual disability, of which four had ID. Three of them with ID had heterozygous variants, while one had compound heterozygous variants. There is also some functional evidence available.

Hence, this gene can be promoted to green rating in the next GMS review.
Intellectual disability v5.555 DOCK4 Achchuthan Shanmugasundram Gene: dock4 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.554 DOCK4 Achchuthan Shanmugasundram Phenotypes for gene: DOCK4 were changed from neuronevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neuronevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.554 DOCK4 Achchuthan Shanmugasundram Phenotypes for gene: DOCK4 were changed from DOCK4-related neurodevelopmental disorder (MONDO:0060490) to neuronevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.553 DOCK4 Achchuthan Shanmugasundram reviewed gene: DOCK4: Rating: GREEN; Mode of pathogenicity: None; Publications: 38526744; Phenotypes: neuronevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.553 GTF3C5 Achchuthan Shanmugasundram Publications for gene: GTF3C5 were set to 38520561; 35503477
Intellectual disability v5.552 GTF3C5 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Zornitza Stark, PMID:35503477 reported a proband with profound developmental delay and PMID:38520561 reported three families with syndromic intellectual disability (ID was mild in one family). There is also functional evidence and evidence from zebrafish model in support of the disease association.

Hence, the gene can be promoted to green rating in the next GMS review.; to: Comment on list classification: As reviewed by Zornitza Stark, PMID:35503477 reported a proband with profound developmental delay and PMID:38520561 reported three families with syndromic intellectual disability (ID was mild in one family). There is also functional evidence and evidence from zebrafish model in support of the disease association.

Hence, this gene can be promoted to green rating in the next GMS review.
Intellectual disability v5.552 GTF3C5 Achchuthan Shanmugasundram edited their review of gene: GTF3C5: Changed publications to: 35503477, 38520561
Intellectual disability v5.552 GTF3C5 Achchuthan Shanmugasundram Classified gene: GTF3C5 as Amber List (moderate evidence)
Intellectual disability v5.552 GTF3C5 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, PMID:35503477 reported a proband with profound developmental delay and PMID:38520561 reported three families with syndromic intellectual disability (ID was mild in one family). There is also functional evidence and evidence from zebrafish model in support of the disease association.

Hence, the gene can be promoted to green rating in the next GMS review.
Intellectual disability v5.552 GTF3C5 Achchuthan Shanmugasundram Gene: gtf3c5 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.551 GTF3C5 Achchuthan Shanmugasundram Phenotypes for gene: GTF3C5 were changed from neurodevelopmental disorder MONDO:0700092, GTF3C5-related to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.550 GTF3C5 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: GTF3C5.
Intellectual disability v5.550 GTF3C5 Achchuthan Shanmugasundram reviewed gene: GTF3C5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal ciliopathies v3.23 CENPF Arina Puzriakova Phenotypes for gene: CENPF were changed from Stromme syndrome, 243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome to Stromme syndrome, OMIM:243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome
Childhood onset dystonia, chorea or related movement disorder v3.78 CENPF Arina Puzriakova Phenotypes for gene: CENPF were changed from Stromme syndrome, 243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome to Stromme syndrome, OMIM:243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome
Neurological ciliopathies v3.20 CENPF Arina Puzriakova Phenotypes for gene: CENPF were changed from Stromme syndrome, 243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome to Stromme syndrome, OMIM:243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome
Ophthalmological ciliopathies v3.7 CENPF Arina Puzriakova Phenotypes for gene: CENPF were changed from Stromme syndrome, 243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome to Stromme syndrome, OMIM:243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome
Intellectual disability v5.550 CENPF Arina Puzriakova Phenotypes for gene: CENPF were changed from Stromme syndrome 243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome to Stromme syndrome, OMIM:243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome
Rare multisystem ciliopathy disorders v1.172 CENPF Arina Puzriakova Phenotypes for gene: CENPF were changed from Stromme syndrome, 243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome to Stromme syndrome, OMIM:243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome
DDG2P v3.90 CENPF Arina Puzriakova Phenotypes for gene: CENPF were changed from Stromme syndrome to Stromme syndrome, OMIM:243605
Fetal anomalies v3.169 CENPF Arina Puzriakova Phenotypes for gene: CENPF were changed from Stromme syndrome, 243605 to Stromme syndrome, OMIM:243605
Unexplained young onset end-stage renal disease v3.42 CENPF Arina Puzriakova Phenotypes for gene: CENPF were changed from Stromme syndrome, 243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome to Stromme syndrome, OMIM:243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome
CAKUT v1.177 CENPF Arina Puzriakova Phenotypes for gene: CENPF were changed from Stromme syndrome, 243605; bilateral renal hypoplasia; Duodenal atresia; Hydronephrosis to Stromme syndrome, OMIM:243605
Limb disorders v4.23 CENPF Arina Puzriakova Phenotypes for gene: CENPF were changed from Polydactyly; Stromme syndrome 243605 to Stromme syndrome, OMIM:243605
Severe microcephaly v4.88 CENPF Arina Puzriakova Phenotypes for gene: CENPF were changed from MPD; microcephalic primordial dwarfism; Stromme syndrome, 243605; Microcephaly to Stromme syndrome, OMIM:243605; Microcephalic primordial dwarfism
Intellectual disability v5.549 GMNN Arina Puzriakova Phenotypes for gene: GMNN were changed from Meier-Gorlin syndrome 6, 616835 to Meier-Gorlin syndrome 6, OMIM:616835
Clefting v4.111 GMNN Arina Puzriakova Phenotypes for gene: GMNN were changed from Meier-Gorlin syndrome 6, 616835 to Meier-Gorlin syndrome 6, OMIM:616835
Severe microcephaly v4.87 GMNN Arina Puzriakova Phenotypes for gene: GMNN were changed from MPD; microcephalic primordial dwarfism; Meier-Gorlin syndrome 6, 616835; MGORS6; primordial dwarfism to Meier-Gorlin syndrome 6, OMIM:616835; Microcephalic primordial dwarfism
Intellectual disability v5.548 IGF1 Arina Puzriakova Phenotypes for gene: IGF1 were changed from Growth retardation with deafness and mental retardation due to IGF1 deficiency, 608747; INSULIN-LIKE GROWTH FACTOR I DEFICIENCY (IGF1 DEFICIENCY) to Insulin-like growth factor I deficiency, OMIM:608747
Monogenic hearing loss v4.39 IGF1 Arina Puzriakova Phenotypes for gene: IGF1 were changed from Growth retardation with deafness and mental retardation due to IGF1 deficiency,608747; GrowthretardationwithdeafnessandmentalretardationduetoIGF1deficiency,608747 to Insulin-like growth factor I deficiency, OMIM:608747
DDG2P v3.89 IGF1 Arina Puzriakova Phenotypes for gene: IGF1 were changed from INSULIN-LIKE GROWTH FACTOR I DEFICIENCY 608747 to Insulin-like growth factor I deficiency, OMIM:608747
Fetal anomalies v3.168 IGF1 Arina Puzriakova Phenotypes for gene: IGF1 were changed from INSULIN-LIKE GROWTH FACTOR I DEFICIENCY to Insulin-like growth factor I deficiency, OMIM:608747
IUGR and IGF abnormalities v1.69 IGF1 Arina Puzriakova Phenotypes for gene: IGF1 were changed from Growth retardation with deafness and mental retardation due to IGF1 deficiency, 608747; Insulin-Like Growth Factor I Deficiency to Insulin-like growth factor I deficiency, OMIM:608747
Silver Russell syndrome v1.13 IGF1 Arina Puzriakova Phenotypes for gene: IGF1 were changed from Growth retardation with deafness and mental retardation due to IGF1 deficiency 608747 to Insulin-like growth factor I deficiency, OMIM:608747
Severe microcephaly v4.86 IGF1 Arina Puzriakova Phenotypes for gene: IGF1 were changed from Growth retardation with deafness and mental retardation due to IGF1 deficiency, 608747; MPD; microcephalic primordial dwarfism to Insulin-like growth factor I deficiency, OMIM:608747; Microcephalic primordial dwarfism
Intellectual disability v5.547 LIG4 Arina Puzriakova Phenotypes for gene: LIG4 were changed from LIG4 syndrome, OMIM:606593 to LIG4 syndrome, OMIM:606593
Haematological malignancies cancer susceptibility v4.5 LIG4 Arina Puzriakova Phenotypes for gene: LIG4 were changed from Class: miscellaneous; Ligase IV syndrome; Lymphoma; ALL to LIG4 syndrome, OMIM:606593; Ligase IV syndrome; Lymphoma; ALL
Intellectual disability v5.547 LIG4 Arina Puzriakova Phenotypes for gene: LIG4 were changed from LIG4 syndrome, 606593{Multiple myeloma, resistance to}, 254500Severe combined immunodeficiency with sensitivity to ionizing radiation, 602450; LIG4 SYNDROME to LIG4 syndrome, OMIM:606593
Fetal anomalies v3.167 LIG4 Arina Puzriakova Phenotypes for gene: LIG4 were changed from SEVERE COMBINED IMMUNODEFICIENCY AUTOSOMAL RECESSIVE T-CELL-NEGATIVE/B-CELL-NEGATIVE/NK-CELL-POSITIVE WITH SENSITIVITY TO IONIZING RADIATION; LIG4 SYNDROME to LIG4 syndrome, OMIM:606593
Cytopenia - NOT Fanconi anaemia v3.34 LIG4 Arina Puzriakova Phenotypes for gene: LIG4 were changed from 606593 LIG4 syndrome to LIG4 syndrome, OMIM:606593
IUGR and IGF abnormalities v1.68 LIG4 Arina Puzriakova Phenotypes for gene: LIG4 were changed from microcephaly, growth retardation, immunodeficiency, developmental delay to LIG4 syndrome, OMIM:606593; microcephaly, growth retardation, immunodeficiency, developmental delay
Haematological malignancies for rare disease v1.18 LIG4 Arina Puzriakova Phenotypes for gene: LIG4 were changed from Class: miscellaneous; Ligase IV syndrome; Lymphoma; ALL to LIG4 syndrome, OMIM:606593; Class: miscellaneous; Ligase IV syndrome; Lymphoma; ALL
Infantile enterocolitis & monogenic inflammatory bowel disease v1.44 LIG4 Arina Puzriakova Phenotypes for gene: LIG4 were changed from SCID; LIG4 syndrome 606593 to LIG4 syndrome, OMIM:606593
Severe microcephaly v4.85 LIG4 Arina Puzriakova Phenotypes for gene: LIG4 were changed from MPD; microcephalic primordial dwarfism; LIG4 syndrome, 606593; microcephaly to LIG4 syndrome, OMIM:606593; Microcephalic primordial dwarfism
Intellectual disability v5.546 ORC1 Arina Puzriakova Phenotypes for gene: ORC1 were changed from Meier-Gorlin syndrome 1, 224690; MEIER-GORLIN SYNDROME 1 to Meier-Gorlin syndrome 1, OMIM:224690
Skeletal dysplasia v4.65 ORC1 Arina Puzriakova Phenotypes for gene: ORC1 were changed from Meier-Gorlin syndrome 1 224690; Meier-Gorlin syndrome 1 224690 to Meier-Gorlin syndrome 1, OMIM:224690
Fetal anomalies v3.166 ORC1 Arina Puzriakova Phenotypes for gene: ORC1 were changed from MEIER-GORLIN SYNDROME 1 to Meier-Gorlin syndrome 1, OMIM:224690
Limb disorders v4.22 ORC1 Arina Puzriakova Phenotypes for gene: ORC1 were changed from Meier-Gorlin syndrome 1 to Meier-Gorlin syndrome 1, OMIM:224690
Deafness and congenital structural abnormalities v1.27 ORC1 Arina Puzriakova Phenotypes for gene: ORC1 were changed from Bilateral Microtia; 224690; Meier Gorlin EPS; causes microtia and syndromic features; Meier-Gorlin syndrome 1 to Meier-Gorlin syndrome 1, OMIM:224690; Bilateral Microtia
IUGR and IGF abnormalities v1.67 ORC1 Arina Puzriakova Phenotypes for gene: ORC1 were changed from microtia, beaked nose, patellar aplasia/hypoplasia, mammary hypoplasia, micrognathia to Meier-Gorlin syndrome 1, OMIM:224690; microtia, beaked nose, patellar aplasia/hypoplasia, mammary hypoplasia, micrognathia
Severe microcephaly v4.84 ORC1 Arina Puzriakova Phenotypes for gene: ORC1 were changed from MPD; microcephalic primordial dwarfism; Meier-Gorlin syndrome 1, 224690 to Meier-Gorlin syndrome 1, OMIM:224690; Microcephalic primordial dwarfism
Intellectual disability v5.545 ORC4 Arina Puzriakova Phenotypes for gene: ORC4 were changed from Meier-Gorlin syndrome 2, 613800 to Meier-Gorlin syndrome 2, OMIM:613800
Fetal anomalies v3.165 ORC4 Arina Puzriakova Phenotypes for gene: ORC4 were changed from MEIER-GORLIN SYNDROME 2 to Meier-Gorlin syndrome 2, OMIM:613800
Skeletal dysplasia v4.64 ORC4 Arina Puzriakova Phenotypes for gene: ORC4 were changed from Meier-Gorlin syndrome 2 613800; Meier-Gorlin syndrome 2 613800 to Meier-Gorlin syndrome 2, OMIM:613800
Deafness and congenital structural abnormalities v1.26 ORC4 Arina Puzriakova Phenotypes for gene: ORC4 were changed from Bilateral Microtia; 613800; Meier-Gorlin EPS; causes syndromic features to Meier-Gorlin syndrome 2, OMIM:613800; Bilateral Microtia
IUGR and IGF abnormalities v1.66 ORC4 Arina Puzriakova Phenotypes for gene: ORC4 were changed from micrognathia, patellar aplasia/hypoplasia, microtia, mammary hypoplasia to Meier-Gorlin syndrome 2, OMIM:613800; micrognathia, patellar aplasia/hypoplasia, microtia, mammary hypoplasia
Severe microcephaly v4.83 ORC4 Arina Puzriakova Phenotypes for gene: ORC4 were changed from MPD; microcephalic primordial dwarfism; Meier-Gorlin syndrome 2, 613800 to Meier-Gorlin syndrome 2, OMIM:613800; Microcephalic primordial dwarfism
Breast cancer pertinent cancer susceptibility v2.8 PTEN Dmitrijs Rots reviewed gene: PTEN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: PHTS; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Arthrogryposis v5.31 COASY Achchuthan Shanmugasundram Classified gene: COASY as Amber List (moderate evidence)
Arthrogryposis v5.31 COASY Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for promoting this gene to green rating in the next GMS review.
Arthrogryposis v5.31 COASY Achchuthan Shanmugasundram Gene: coasy has been classified as Amber List (Moderate Evidence).
Arthrogryposis v5.30 COASY Achchuthan Shanmugasundram Phenotypes for gene: COASY were changed from Pontocerebellar hypoplasia, type 12, OMIM:618266; pontocerebellar hypoplasia, type 12, MONDO:0032643 to Neurodegeneration with brain iron accumulation 6, OMIM:615643; Pontocerebellar hypoplasia, type 12, OMIM:618266; arthrogryposis, MONDO:0008779
Arthrogryposis v5.29 COASY Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: COASY.
Tag Q2_24_NHS_review tag was added to gene: COASY.
Arthrogryposis v5.29 COASY Achchuthan Shanmugasundram reviewed gene: COASY: Rating: GREEN; Mode of pathogenicity: None; Publications: 30089828, 35499143, 36495139; Phenotypes: Neurodegeneration with brain iron accumulation 6, OMIM:615643, Pontocerebellar hypoplasia, type 12, OMIM:618266, arthrogryposis, MONDO:0008779; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v5.29 PIP5K1C Achchuthan Shanmugasundram Phenotypes for gene: PIP5K1C were changed from Lethal congenital contractural syndrome 3 611369 to Lethal congenital contractural syndrome 3, OMIM:611369
Arthrogryposis v5.28 PIP5K1C Achchuthan Shanmugasundram Publications for gene: PIP5K1C were set to 17701898
Arthrogryposis v5.27 PIP5K1C Achchuthan Shanmugasundram Classified gene: PIP5K1C as Amber List (moderate evidence)
Arthrogryposis v5.27 PIP5K1C Achchuthan Shanmugasundram Added comment: Comment on list classification: As there are three unrelated cases with biallelic variants (two unrelated cases with the same homozygous variant and two foetuses from one family with compound heterozygous variants), this gene can be promoted to green rating in the next GMS update.
Arthrogryposis v5.27 PIP5K1C Achchuthan Shanmugasundram Gene: pip5k1c has been classified as Amber List (Moderate Evidence).
Arthrogryposis v5.26 PIP5K1C Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: PIP5K1C.
Tag Q2_24_NHS_review tag was added to gene: PIP5K1C.
Arthrogryposis v5.26 PIP5K1C Achchuthan Shanmugasundram reviewed gene: PIP5K1C: Rating: GREEN; Mode of pathogenicity: None; Publications: 17701898, 38491417; Phenotypes: Lethal congenital contractural syndrome 3, OMIM:611369; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v5.26 TRIP4 Achchuthan Shanmugasundram reviewed gene: TRIP4: Rating: AMBER; Mode of pathogenicity: None; Publications: 31794073; Phenotypes: Spinal muscular atrophy with congenital bone fractures 1, OMIM:616866, ?Muscular dystrophy, congenital, Davignon-Chauveau type, OMIM:617066; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v5.26 COASY Achchuthan Shanmugasundram Publications for gene: COASY were set to 11980892; 25778941; 24360804; 27021474; 28489334; 30089828; 36495139
Ectodermal dysplasia v3.29 TWIST2 Dmitrijs Rots gene: TWIST2 was added
gene: TWIST2 was added to Ectodermal dysplasia. Sources: Expert Review
Mode of inheritance for gene: TWIST2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TWIST2 were set to Focal facial dermal dysplasia 3, Setleis type
Review for gene: TWIST2 was set to GREEN
Added comment: Included as differential for ectodermal dysplasia
Sources: Expert Review
Arthrogryposis v5.25 SLC18A3 Achchuthan Shanmugasundram Classified gene: SLC18A3 as Amber List (moderate evidence)
Arthrogryposis v5.25 SLC18A3 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Hannah Knight, PMID:34943989 reports an additional patient with compound heterozygous variants in SLC18A3 gene and presenting with arthrogryposis congenital (AMC). Hence, there is sufficient evidence available for promoting this gene to green rating in the next GMS review.
Arthrogryposis v5.25 SLC18A3 Achchuthan Shanmugasundram Gene: slc18a3 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v5.24 SLC18A3 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: SLC18A3.
Tag Q2_24_NHS_review tag was added to gene: SLC18A3.
Arthrogryposis v5.24 SLC18A3 Achchuthan Shanmugasundram edited their review of gene: SLC18A3: Changed phenotypes to: Myasthenic syndrome, congenital, 21, presynaptic, OMIM:617239, arthrogryposis, MONDO:0008779
Arthrogryposis v5.24 SLC18A3 Achchuthan Shanmugasundram Phenotypes for gene: SLC18A3 were changed from Myasthenic syndrome, congenital, 21, presynaptic, 617239; arthrogryposis to Myasthenic syndrome, congenital, 21, presynaptic, OMIM:617239; arthrogryposis, MONDO:0008779
Arthrogryposis v5.23 SLC18A3 Achchuthan Shanmugasundram Publications for gene: SLC18A3 were set to 28188302; 27590285; 31059209
Arthrogryposis v5.22 SLC18A3 Achchuthan Shanmugasundram reviewed gene: SLC18A3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v4.63 ORC6 Arina Puzriakova Phenotypes for gene: ORC6 were changed from Meier-Gorlin syndrome 3 613803; Meier-Gorlin syndrome 3 613803 to Meier-Gorlin syndrome 3, OMIM:613803
Intellectual disability v5.544 ORC6 Arina Puzriakova Phenotypes for gene: ORC6 were changed from Meier-Gorlin syndrome 3, 613803 to Meier-Gorlin syndrome 3, OMIM:613803
Fetal anomalies v3.164 ORC6 Arina Puzriakova Phenotypes for gene: ORC6 were changed from MEIER-GORLIN SYNDROME 3 to Meier-Gorlin syndrome 3, OMIM:613803
Deafness and congenital structural abnormalities v1.25 ORC6 Arina Puzriakova Phenotypes for gene: ORC6 were changed from Bilateral Microtia; 613803; Meier-Gorlin EPS; causes syndromic features; Meier-Gorlin syndrome 3 to Meier-Gorlin syndrome 3, OMIM:613803; Bilateral Microtia
IUGR and IGF abnormalities v1.65 ORC6 Arina Puzriakova Phenotypes for gene: ORC6 were changed from micrognathia, patellar aplasia/hypoplasia, microtia, mammary hypoplasia to Meier-Gorlin syndrome 3, OMIM:613803; micrognathia, patellar aplasia/hypoplasia, microtia, mammary hypoplasia
Severe microcephaly v4.82 ORC6 Arina Puzriakova Phenotypes for gene: ORC6 were changed from MPD; microcephalic primordial dwarfism; Meier-Gorlin syndrome 3, 613803 to Meier-Gorlin syndrome 3, OMIM:613803; Microcephalic primordial dwarfism
Insulin resistance (including lipodystrophy) v1.17 PCNT Arina Puzriakova Phenotypes for gene: PCNT were changed from Microcephalic osteodysplastic primordial dwarfism, type II 210720; Osteodysplastic Primordial Dwarfism of Majewski Tyoe 2; Severe Insulin Resistance to Microcephalic osteodysplastic primordial dwarfism, type II, OMIM:210720; Insulin resistance, HP:0000855
IUGR and IGF abnormalities v1.64 PCNT Arina Puzriakova Phenotypes for gene: PCNT were changed from Seckel syndrome, MOPD type II - growth restrction, microcephaly, prominent nose, micrognathia, squeaky voice, insulin resistance to Microcephalic osteodysplastic primordial dwarfism, type II, OMIM:210720
Limb disorders v4.21 PCNT Arina Puzriakova Phenotypes for gene: PCNT were changed from Microcephalic osteodysplastic primordial dwarfism, type II 210720 to Microcephalic osteodysplastic primordial dwarfism, type II, OMIM:210720
Skeletal dysplasia v4.62 PCNT Arina Puzriakova Phenotypes for gene: PCNT were changed from Microcephalic osteodysplastic primordial dwarfism, type II 210720 to Microcephalic osteodysplastic primordial dwarfism, type II, OMIM:210720
DDG2P v3.88 PCNT Arina Puzriakova Phenotypes for gene: PCNT were changed from MICROCEPHALIC OSTEODYSPLASTIC PRIMORDIAL DWARFISM, TYPE II 210720 to Microcephalic osteodysplastic primordial dwarfism, type II, OMIM:210720
Fetal anomalies v3.163 PCNT Arina Puzriakova Phenotypes for gene: PCNT were changed from MICROCEPHALIC OSTEODYSPLASTIC PRIMORDIAL DWARFISM, TYPE II to Microcephalic osteodysplastic primordial dwarfism, type II, OMIM:210720
Intellectual disability v5.543 PCNT Arina Puzriakova Phenotypes for gene: PCNT were changed from Microcephalic osteodysplastic primordial dwarfism, type II, 210720 -3; MICROCEPHALIC OSTEODYSPLASTIC PRIMORDIAL DWARFISM, TYPE II to Microcephalic osteodysplastic primordial dwarfism, type II, OMIM:210720
Severe microcephaly v4.81 PCNT Arina Puzriakova Phenotypes for gene: PCNT were changed from MPD; microcephalic primordial dwarfism; Microcephalic Osteodysplastic Primordial Dwarfism; Microcephalic osteodysplastic primordial dwarfism, type II, 210720 to Microcephalic osteodysplastic primordial dwarfism, type II, OMIM:210720; Microcephalic primordial dwarfism
Retinal disorders v4.90 RNU4ATAC Arina Puzriakova Phenotypes for gene: RNU4ATAC were changed from Lowry-Wood syndrome, OMIM:226960; Microcephalic osteodysplastic primordial dwarfism, type I, OMIM:210710; Roifman syndrome, OMIM:616651 to Lowry-Wood syndrome, OMIM:226960; Roifman syndrome, OMIM:616651
Intellectual disability v5.542 RNU4ATAC Arina Puzriakova Phenotypes for gene: RNU4ATAC were changed from Gene2Phenotype confirmed gene with ID HPO to Lowry-Wood syndrome, OMIM:226960; Microcephalic osteodysplastic primordial dwarfism, type I, OMIM:210710; Roifman syndrome, OMIM:616651
Early onset or syndromic epilepsy v4.196 RNU4ATAC Arina Puzriakova Phenotypes for gene: RNU4ATAC were changed from Microcephalic osteodysplastic primordial dwarfism, type I 210710 to Microcephalic osteodysplastic primordial dwarfism, type I, OMIM:210710
Fetal anomalies v3.162 RNU4ATAC Arina Puzriakova Phenotypes for gene: RNU4ATAC were changed from MICROCEPHALIC OSTEODYSPLASTIC PRIMORDIAL DWARFISM, TYPE I to Microcephalic osteodysplastic primordial dwarfism, type I, OMIM:210710
Cytopenia - NOT Fanconi anaemia v3.33 RNU4ATAC Arina Puzriakova Phenotypes for gene: RNU4ATAC were changed from Roifman syndrome, 616651; Microcephalic osteodysplastic primordial dwarfism, type I, 210710 to Roifman syndrome, OMIM:616651
Bleeding and platelet disorders v3.10 RNU4ATAC Arina Puzriakova Phenotypes for gene: RNU4ATAC were changed from Microcephalic osteodysplastic primordial dwarfism, type I / Roifman syndrome to Roifman syndrome, OMIM:616651
Inherited bleeding disorders v1.178 RNU4ATAC Arina Puzriakova Phenotypes for gene: RNU4ATAC were changed from Platelet disorder; Roifman Syndrome with thrombocytopenia and Primary immunodeficiency to Roifman syndrome, OMIM:616651; Roifman Syndrome with thrombocytopenia and Primary immunodeficiency
Skeletal dysplasia v4.61 RNU4ATAC Arina Puzriakova Phenotypes for gene: RNU4ATAC were changed from Roifman syndrome 616651; Microcephalic osteodysplastic primordial dwarfism, type I 210710 to Lowry-Wood syndrome, OMIM:226960; Microcephalic osteodysplastic primordial dwarfism, type I, OMIM:210710; Roifman syndrome, OMIM:616651
Limb disorders v4.20 RNU4ATAC Arina Puzriakova Phenotypes for gene: RNU4ATAC were changed from Microcephalic osteodysplastic primordial dwarfism, type I 210710; Roifman syndrome 616651 to Lowry-Wood syndrome, OMIM:226960; Microcephalic osteodysplastic primordial dwarfism, type I, OMIM:210710; Roifman syndrome, OMIM:616651
Primary immunodeficiency or monogenic inflammatory bowel disease v4.202 RNU4ATAC Arina Puzriakova Phenotypes for gene: RNU4ATAC were changed from Recurrent bacterial infections, lymphadenopathy, Spondyloepiphyseal dysplasia, extreme intrauterine growth retardation, retinal dystrophy, facial dysmorphism, may present with microcephaly, short stature; Recurrent bacterial infections, lymphadenopathy, Spondyloepiphyseal dysplasia, extreme intrauterine growth retardation, retinal dystrophy, facial dysmorphism, may present with microcephaly; Combined immunodeficiencies with associated or syndromic features to Roifman syndrome, OMIM:616651; Recurrent bacterial infections, lymphadenopathy, Spondyloepiphyseal dysplasia, extreme intrauterine growth retardation, retinal dystrophy, facial dysmorphism, may present with microcephaly
COVID-19 research v1.142 RNU4ATAC Arina Puzriakova Phenotypes for gene: RNU4ATAC were changed from Recurrent bacterial infections, lymphadenopathy, Spondyloepiphyseal dysplasia, extreme intrauterine growth retardation, retinal dystrophy, facial dysmorphism, may present with microcephaly; Combined immunodeficiencies with associated or syndromic features; Recurrent bacterial infections, lymphadenopathy, Spondyloepiphyseal dysplasia, extreme intrauterine growth retardation, retinal dystrophy, facial dysmorphism, may present with microcephaly, short stature to Roifman syndrome, OMIM:616651; Recurrent bacterial infections, lymphadenopathy, Spondyloepiphyseal dysplasia, extreme intrauterine growth retardation, retinal dystrophy, facial dysmorphism, may present with microcephaly
Severe microcephaly v4.80 RNU4ATAC Arina Puzriakova Phenotypes for gene: RNU4ATAC were changed from Microcephalic osteodysplastic primordial dwarfism, type I; Microcephalic osteodysplastic primordial dwarfism, type I, 210710; MPD; microcephalic primordial dwarfism to Microcephalic osteodysplastic primordial dwarfism, type I, OMIM:210710; Lowry-Wood syndrome, OMIM:226960; Microcephalic primordial dwarfism
Intellectual disability v5.541 TRAIP Arina Puzriakova Phenotypes for gene: TRAIP were changed from Seckel syndrome 9, 616777 to Seckel syndrome 9, OMIM:616777
Cerebral vascular malformations v3.16 TRAIP Arina Puzriakova Phenotypes for gene: TRAIP were changed from Seckel syndrome 9 616777 to Seckel syndrome 9, OMIM:616777
Fetal anomalies v3.161 TRAIP Arina Puzriakova Phenotypes for gene: TRAIP were changed from Seckel syndrome 9 to Seckel syndrome 9, OMIM:616777
Severe microcephaly v4.79 TRAIP Arina Puzriakova Phenotypes for gene: TRAIP were changed from MPD; microcephalic primordial dwarfism; Seckel syndrome 9, 616777; Microcephaly to Seckel syndrome 9, OMIM:616777; Microcephalic primordial dwarfism
Mitochondrial disorders v4.169 XRCC4 Arina Puzriakova Mode of inheritance for gene: XRCC4 was changed from to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v4.169 XRCC4 Arina Puzriakova Phenotypes for gene: XRCC4 were changed from Short stature, microcephaly, and endocrine dysfunction 616541 to Short stature, microcephaly, and endocrine dysfunction, OMIM:616541
Fetal anomalies v3.160 XRCC4 Arina Puzriakova Phenotypes for gene: XRCC4 were changed from PRIMORDIAL DWARFISM to Short stature, microcephaly, and endocrine dysfunction, OMIM:616541
Skeletal dysplasia v4.60 XRCC4 Arina Puzriakova Phenotypes for gene: XRCC4 were changed from Short stature, microcephaly, and endocrine dysfunction 616541 to Short stature, microcephaly, and endocrine dysfunction, OMIM:616541
Intellectual disability v5.540 XRCC4 Arina Puzriakova Phenotypes for gene: XRCC4 were changed from PRIMORDIAL DWARFISM to Short stature, microcephaly, and endocrine dysfunction, OMIM:616541
IUGR and IGF abnormalities v1.63 XRCC4 Arina Puzriakova Phenotypes for gene: XRCC4 were changed from short stature, microcephaly, hypothyroidism, diabetes mellitus, progressive ataxia, hypergonadotrophic hypogonadism to Short stature, microcephaly, and endocrine dysfunction, OMIM:616541; Short stature, microcephaly, hypothyroidism, diabetes mellitus, progressive ataxia, hypergonadotrophic hypogonadism
Severe microcephaly v4.78 XRCC4 Arina Puzriakova Phenotypes for gene: XRCC4 were changed from MPD; microcephalic primordial dwarfism; Short stature, microcephaly, and endocrine dysfunction, 616541 to Short stature, microcephaly, and endocrine dysfunction, OMIM:616541; Microcephalic primordial dwarfism
Severe microcephaly v4.77 ATRIP Arina Puzriakova Publications for gene: ATRIP were set to
Severe microcephaly v4.76 ATRIP Arina Puzriakova Mode of inheritance for gene: ATRIP was changed from to BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly v4.75 ATRIP Arina Puzriakova Phenotypes for gene: ATRIP were changed from MPD; microcephalic primordial dwarfism; severe microcephaly (-10 SD), micrognathia, dental crowding, small earlobes, delayed bone age, and symmetric dwarfism to Microcephalic primordial dwarfism; Severe microcephaly (-10 SD), micrognathia, dental crowding, small earlobes, delayed bone age, and symmetric dwarfism
Intellectual disability v5.539 CDC6 Arina Puzriakova Phenotypes for gene: CDC6 were changed from MEIER-GORLIN SYNDROME 5 to Meier-Gorlin syndrome 5, OMIM:613805
Skeletal dysplasia v4.59 CDC6 Arina Puzriakova Phenotypes for gene: CDC6 were changed from Meier-Gorlin syndrome 5 613805 to Meier-Gorlin syndrome 5, OMIM:613805
Fetal anomalies v3.159 CDC6 Arina Puzriakova Phenotypes for gene: CDC6 were changed from MEIER-GORLIN SYNDROME 5 to Meier-Gorlin syndrome 5, OMIM:613805
Deafness and congenital structural abnormalities v1.24 CDC6 Arina Puzriakova Phenotypes for gene: CDC6 were changed from Bilateral Microtia; 613805; Meier-Gorlin syndrome 5, 613805; Neurology panel; Bilateral Microtia, 613805; Causes Meier-Gorlin EPS; syndromic features to Meier-Gorlin syndrome 5, OMIM:613805; Bilateral Microtia
IUGR and IGF abnormalities v1.62 CDC6 Arina Puzriakova Phenotypes for gene: CDC6 were changed from patellar hypoplasia/aplasia, microtia, meier-gorlin syndrome, mammary hypoplasia to Meier-Gorlin syndrome 5, OMIM:613805; patellar hypoplasia/aplasia, microtia, meier-gorlin syndrome, mammary hypoplasia
Severe microcephaly v4.74 CDC6 Arina Puzriakova Phenotypes for gene: CDC6 were changed from MPD; microcephalic primordial dwarfism; ?Meier-Gorlin syndrome 5, 613805 to Meier-Gorlin syndrome 5, OMIM:613805; Microcephalic primordial dwarfism
Severe microcephaly v4.73 CENPE Arina Puzriakova Phenotypes for gene: CENPE were changed from ?Microcephaly 13, primary, autosomal recessive, 616051; MPD; microcephalic primordial dwarfism to ?Microcephaly 13, primary, autosomal recessive, OMIM:616051; Microcephalic primordial dwarfism
Intellectual disability v5.538 CDT1 Arina Puzriakova Phenotypes for gene: CDT1 were changed from MEIER-GORLIN SYNDROME 4 to Meier-Gorlin syndrome 4, OMIM:613804
Skeletal dysplasia v4.58 CDT1 Arina Puzriakova Phenotypes for gene: CDT1 were changed from Meier-Gorlin syndrome 4 613804 to Meier-Gorlin syndrome 4, OMIM:613804
Fetal anomalies v3.158 CDT1 Arina Puzriakova Phenotypes for gene: CDT1 were changed from MEIER-GORLIN SYNDROME 4 to Meier-Gorlin syndrome 4, OMIM:613804
Deafness and congenital structural abnormalities v1.23 CDT1 Arina Puzriakova Phenotypes for gene: CDT1 were changed from Bilateral Microtia; 613804; Meier-Gorlin syndrome 4, 613804; Causes Meier-Gorlin EPS; syndromic features; Short stature, small head size, the ears may be low-set or rotated backward (+/-microtia). Additional features can include a small mouth (microstomia), an underdeveloped lower jaw (micrognathia), full lips, and a narrow nose with a high nasal bridge to Meier-Gorlin syndrome 4, OMIM:613804; Short stature, small head size, the ears may be low-set or rotated backward (+/-microtia). Additional features can include a small mouth (microstomia), an underdeveloped lower jaw (micrognathia), full lips, and a narrow nose with a high nasal bridge
IUGR and IGF abnormalities v1.61 CDT1 Arina Puzriakova Phenotypes for gene: CDT1 were changed from micrognathia, microtia, patellar hypoplasia/aplasia, mammary hypoplasia to Meier-Gorlin syndrome 4, OMIM:613804; micrognathia, microtia, patellar hypoplasia/aplasia, mammary hypoplasia
Severe microcephaly v4.72 CDT1 Arina Puzriakova Phenotypes for gene: CDT1 were changed from MPD; microcephalic primordial dwarfism; Meier-Gorlin syndrome 4, 613804 to Meier-Gorlin syndrome 4, OMIM:613804; Microcephalic primordial dwarfism
Monogenic diabetes v2.58 BLM Arina Puzriakova Phenotypes for gene: BLM were changed from Bloom syndrome to Bloom syndrome, OMIM:210900
Pigmentary skin disorders v3.12 BLM Arina Puzriakova Phenotypes for gene: BLM were changed from Bloom syndrome to Bloom syndrome, OMIM:210900
Primary ovarian insufficiency v1.68 BLM Arina Puzriakova Phenotypes for gene: BLM were changed from Bloom syndrome 210900 to Bloom syndrome, OMIM:210900
IUGR and IGF abnormalities v1.60 BLM Arina Puzriakova Phenotypes for gene: BLM were changed from Bloom syndrome, 210900 to Bloom syndrome, OMIM:210900
Haematological malignancies for rare disease v1.17 BLM Arina Puzriakova Phenotypes for gene: BLM were changed from Class: BM failure syndrome (typ AR); Bloom syndrome; leukaemia; lymphoma; skin squamous cell; other tumour types; Lymphoma; ALL; MDS; AML; Leukaemia; Carcinomas to Bloom syndrome, OMIM:210900; Class: BM failure syndrome (typ AR); Bloom syndrome; leukaemia; lymphoma; skin squamous cell; other tumour types; Lymphoma; ALL; MDS; AML; Leukaemia; Carcinomas
Severe microcephaly v4.71 BLM Arina Puzriakova Phenotypes for gene: BLM were changed from Bloom syndrome, OMIM:210900 to Bloom syndrome, OMIM:210900; Microcephalic primordial dwarfism
Hereditary haemorrhagic telangiectasia v3.6 ATR Arina Puzriakova Phenotypes for gene: ATR were changed from Cutaneous telangiectasia and cancer syndrome, familial, 614564 (biallelic) to ?Cutaneous telangiectasia and cancer syndrome, familial, OMIM:614564
Intellectual disability v5.537 ATR Arina Puzriakova Phenotypes for gene: ATR were changed from Seckel syndrome 1, 210600Cutaneous telangiectasia and cancer syndrome, familial, 614564; SECKEL SYNDROME TYPE 1 (SCKL1) to Seckel syndrome 1, OMIM:210600
Clefting v4.110 ATR Arina Puzriakova Phenotypes for gene: ATR were changed from SECKEL SYNDROME 1; SCKL1 to Seckel syndrome 1, OMIM:210600
Clefting v4.110 ATR Arina Puzriakova Mode of inheritance for gene: ATR was changed from to BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly v4.70 ATR Arina Puzriakova Publications for gene: ATR were set to
Severe microcephaly v4.69 ATR Arina Puzriakova Phenotypes for gene: ATR were changed from MPD; microcephalic primordial dwarfism; Seckel syndrome 1, 210600; MICROCEPHALIC PRIMORDIAL DWARFISM I to Seckel syndrome 1, OMIM:210600; Microcephalic primordial dwarfism
Intellectual disability v5.536 FEM1B Zornitza Stark edited their review of gene: FEM1B: Added comment: Five individuals reported now with same recurrent missense variant, NM_015322.5:c.377G>A NP_056137.1:p.(Arg126Gln). Affected individuals shared a severe neurodevelopmental disorder with behavioral phenotypes and a variable set of malformations, including brain anomalies, clubfeet, skeletal abnormalities, and facial dysmorphism. Overexpression of the the FEM1BR126Q variant but not FEM1B wild-type protein, during mouse brain development, resulted in delayed neuronal migration of the target cells.; Changed rating: GREEN; Changed publications to: 31036916, 38465576; Changed phenotypes to: Syndromic disease MONDO:0002254, FEM1B-related
Fetal anomalies v3.157 USP14 Zornitza Stark gene: USP14 was added
gene: USP14 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: USP14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: USP14 were set to 38469793
Phenotypes for gene: USP14 were set to Syndromic disease MONDO:0002254, USP14-related
Review for gene: USP14 was set to AMBER
Added comment: PMID 38469793: biallelic USP14 variants in four individuals from three unrelated families: one fetus, a newborn with a syndromic NDD, and two siblings affected by a progressive neurological disease. Specifically, the two siblings from the latter family carried two compound heterozygous variants c.8T>C p.(Leu3Pro) and c.988C>T p.(Arg330*), while the fetus had a homozygous frameshift c.899_902del p.(Lys300Serfs*24) variant and the newborn patient harbored a homozygous frameshift c.233_236del p.(Leu78Glnfs*11) variant. The fetus and the newborn had extensive brain malformations.
Sources: Literature
Intellectual disability v5.536 RNU4-2 Zornitza Stark gene: RNU4-2 was added
gene: RNU4-2 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: RNU4-2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RNU4-2 were set to 38645094
Phenotypes for gene: RNU4-2 were set to Neurodevelopmental disorder, MONDO:0700092, RNU4-2 related
Review for gene: RNU4-2 was set to GREEN
Added comment: Over 100 individuals reported with NND and heterozygous variants in a 18 bp region of RNU4-2 mapping to two structural elements in the U4/U6 snRNA duplex (the T-loop and Stem III). The vast majority of individuals (77.3%) have the same highly recurrent single base-pair insertion (n.64_65insT). Variants in this region likely explain 0.41% of individuals with NDD.
Sources: Literature
Intellectual disability v5.536 ACBD6 Arina Puzriakova Added comment: Comment on phenotypes: This gene now has a relevant phenotype listed in OMIM (MIM# 620785)
Intellectual disability v5.536 ACBD6 Arina Puzriakova Phenotypes for gene: ACBD6 were changed from Neurodevelopmental disorder, MONDO:0700092 to Neurodevelopmental disorder with progressive movement abnormalities, OMIM:620785
Childhood onset dystonia, chorea or related movement disorder v3.77 ACBD6 Arina Puzriakova Added comment: Comment on phenotypes: This gene now has a relevant phenotype listed in OMIM (MIM# 620785)
Childhood onset dystonia, chorea or related movement disorder v3.77 ACBD6 Arina Puzriakova Phenotypes for gene: ACBD6 were changed from Neurodevelopmental disorder, MONDO:0700092 to Neurodevelopmental disorder with progressive movement abnormalities, OMIM:620785
Childhood onset hereditary spastic paraplegia v4.43 ACBD6 Arina Puzriakova Added comment: Comment on phenotypes: This gene now has a relevant phenotype listed in OMIM (MIM# 620785)
Childhood onset hereditary spastic paraplegia v4.43 ACBD6 Arina Puzriakova Phenotypes for gene: ACBD6 were changed from Neurodevelopmental disorder, MONDO:0700092 to Neurodevelopmental disorder with progressive movement abnormalities, OMIM:620785
Severe microcephaly v4.68 ACBD6 Arina Puzriakova Added comment: Comment on phenotypes: This gene now has a relevant phenotype listed in OMIM (MIM# 620785)
Severe microcephaly v4.68 ACBD6 Arina Puzriakova Phenotypes for gene: ACBD6 were changed from Neurodevelopmental disorder, MONDO:0700092 to Neurodevelopmental disorder with progressive movement abnormalities, OMIM:620785
Ataxia and cerebellar anomalies - narrow panel v4.64 ACBD6 Arina Puzriakova Added comment: Comment on phenotypes: This gene now has a relevant phenotype listed in OMIM (MIM# 620785)
Ataxia and cerebellar anomalies - narrow panel v4.64 ACBD6 Arina Puzriakova Phenotypes for gene: ACBD6 were changed from Neurodevelopmental disorder, MONDO:0700092 to Neurodevelopmental disorder with progressive movement abnormalities, OMIM:620785
Paediatric disorders - additional genes v3.10 PLD1 Arina Puzriakova changed review comment from: Comment on list classification: This Green gene was signed off in Nov 2022 but now flagging for another review by the GMS specialist group in the context of the conflicting Red review by Jesse Hayesmoore (Oxford Regional Genetics Laboratory) to determine whether this gene should be downgraded.; to: Comment on list classification: This Green gene was signed off in Mar 2023 but now flagging for another review by the GMS specialist group in the context of the conflicting Red review by Jesse Hayesmoore (Oxford Regional Genetics Laboratory) to determine whether this gene should be downgraded.
Fetal anomalies v3.157 PLD1 Arina Puzriakova changed review comment from: Comment on list classification: This Green gene was signed off in Nov 2022 but now flagging for another review by the GMS specialist group in the context of the conflicting Red review by Jesse Hayesmoore (Oxford Regional Genetics Laboratory) to determine whether this gene should be downgraded.; to: Comment on list classification: This Green gene was signed off in Mar 2023 but now flagging for another review by the GMS specialist group in the context of the conflicting Red review by Jesse Hayesmoore (Oxford Regional Genetics Laboratory) to determine whether this gene should be downgraded.
Paediatric disorders - additional genes v3.10 PLD1 Arina Puzriakova Classified gene: PLD1 as Green List (high evidence)
Paediatric disorders - additional genes v3.10 PLD1 Arina Puzriakova Added comment: Comment on list classification: This Green gene was signed off in Nov 2022 but now flagging for another review by the GMS specialist group in the context of the conflicting Red review by Jesse Hayesmoore (Oxford Regional Genetics Laboratory) to determine whether this gene should be downgraded.
Paediatric disorders - additional genes v3.10 PLD1 Arina Puzriakova Gene: pld1 has been classified as Green List (High Evidence).
Fetal anomalies v3.157 PLD1 Arina Puzriakova Classified gene: PLD1 as Green List (high evidence)
Fetal anomalies v3.157 PLD1 Arina Puzriakova Added comment: Comment on list classification: This Green gene was signed off in Nov 2022 but now flagging for another review by the GMS specialist group in the context of the conflicting Red review by Jesse Hayesmoore (Oxford Regional Genetics Laboratory) to determine whether this gene should be downgraded.
Fetal anomalies v3.157 PLD1 Arina Puzriakova Gene: pld1 has been classified as Green List (High Evidence).
Fetal anomalies v3.156 PLD1 Arina Puzriakova Tag Q2_24_demote_red tag was added to gene: PLD1.
Tag Q2_24_expert_review tag was added to gene: PLD1.
Paediatric disorders - additional genes v3.9 PLD1 Arina Puzriakova Tag Q2_24_demote_red tag was added to gene: PLD1.
Tag Q2_24_expert_review tag was added to gene: PLD1.
Paediatric disorders - additional genes v3.9 PLD1 Arina Puzriakova commented on gene: PLD1: Copied review from Paediatric or syndromic cardiomyopathy (749) v3.43 panel:

Jesse Hayesmoore (Oxford Regional Genetics Laboratory)
Red List (low evidence)

"On the basis of functional data described in PMIDs: 27799408 and 33645542, PLD1 certainly seems to be a plausible functional candidate for causality of cardiac valvular defects. The main paper linking this gene with congenital heart disease / cardiomyopathy is Lahrouchi et al. (2021; PMID: 33645542; note this also includes the same 2 cases as described in Ta-Shma et al. 2017 PMID: 27799408). The paper presents 19 families with severe fetal- / neonatal-onset congenital heart (mainly valvular) defects and 2 with cardiomyopathy where affected babies were homozygous or compound heterozygous for PLD1 variants. The paper also provides some functional analysis of missense variants detected, showing that many but not all of them result significant loss of PLD1 function. Unfortunately, the paper does not include a LOD score, and there is very little cosegregation data presented for any of the variants. In addition, 4 of the 31 variants they promote as pathogenic for autosomal recessive disease are detected in multiple homozygous individuals on gnomAD, which I think provides significant evidence that they might not be pathogenic for a severe autosomal recessive condition. Most notably, 1 of the variants (i.e. I668F), which the authors promote as a pathogenic Ashkenazi Jewish founder variant (but which is also fairly frequent in non-Finnish Europeans) is detected in 7 homozygotes on gnomAD and was found to have ~80% loss of PLD1 function in their assay. This suggests that significant loss of function of this gene (i.e. down to 20%) might not be causative of a severe recessive condition (that is not to say that total or near total loss of function is not causative). Three other of the variants promoted as pathogenic in this article are also detected in homozygotes on gnomAD.

I think one of the major pieces of missing information required to make a full assessment of this gene’s linkage to disease is that is unknown how frequent biallelic (apparently loss of function) variant genotypes are in the general population or in healthy control individuals. Although homozygosity for any one variant can be determined from gnomAD, compound heterozygosity (which is likely to represent the vast majority of biallelic genotypes) cannot be assessed on gnomAD, and I can find no record in the literature of this being assessed in a normal control cohort. Without this information, we cannot know whether biallelic PLD1 genotypes are specific to babies with this severe phenotype. Without knowing this, and in the absence of any significant cosegregation data for any variant, there is no reasonable basis upon which one can conclude that this is a valid autosomal recessive gene for the phenotype. Without such validation, PVS1 cannot be applied for any apparent loss of function variant. Given this, and the general lack of cosegregation data for any one variant, I do not believe there is any PLD1 variant reported in the literature that could be classified as anything but uncertain significance (if not benign or likely benign) on the basis of current variant classification guidelines. Also, there are only two cases of biallelic variants in neonates where the primary phenotype is cardiomyopathy, and of these only one was dilated cardiomyopathy (the other was histiocytoid cardiomyopathy). Hence, the evidence linking this gene to cardiomyopathy is even weaker than it is for valvular defects. I, therefore, do not feel there is sufficient evidence to justify this gene being tested as part of the R135 paediatric cardiomyopathy gene panel.

Other papers (e.g. PMIDs: 33142350, 35380090, 36923242, 37770978) reporting a link between PLD1 genotypes and early onset cardiac disease (not cardiomyopathy) have been published. However, again, I do not think there is sufficient data in the articles to allow any of the variants detected to be confidently classified as anything but VUS according to current variant classification guidelines."
Created: 31 Jan 2024, 12:04 p.m. | Last Modified: 31 Jan 2024, 12:17 p.m
Paediatric or syndromic cardiomyopathy v3.47 PLD1 Arina Puzriakova Classified gene: PLD1 as Green List (high evidence)
Paediatric or syndromic cardiomyopathy v3.47 PLD1 Arina Puzriakova Added comment: Comment on list classification: This Green gene was signed off in Nov 2022 but now flagging for another review by the GMS specialist group in the context of the conflicting Red review by Jesse Hayesmoore (Oxford Regional Genetics Laboratory) to determine whether this gene should be downgraded.
Paediatric or syndromic cardiomyopathy v3.47 PLD1 Arina Puzriakova Gene: pld1 has been classified as Green List (High Evidence).
Fetal anomalies v3.156 PLD1 Arina Puzriakova commented on gene: PLD1: Copied review from Paediatric or syndromic cardiomyopathy (749) v3.43 panel:

Jesse Hayesmoore (Oxford Regional Genetics Laboratory)
Red List (low evidence)

"On the basis of functional data described in PMIDs: 27799408 and 33645542, PLD1 certainly seems to be a plausible functional candidate for causality of cardiac valvular defects. The main paper linking this gene with congenital heart disease / cardiomyopathy is Lahrouchi et al. (2021; PMID: 33645542; note this also includes the same 2 cases as described in Ta-Shma et al. 2017 PMID: 27799408). The paper presents 19 families with severe fetal- / neonatal-onset congenital heart (mainly valvular) defects and 2 with cardiomyopathy where affected babies were homozygous or compound heterozygous for PLD1 variants. The paper also provides some functional analysis of missense variants detected, showing that many but not all of them result significant loss of PLD1 function. Unfortunately, the paper does not include a LOD score, and there is very little cosegregation data presented for any of the variants. In addition, 4 of the 31 variants they promote as pathogenic for autosomal recessive disease are detected in multiple homozygous individuals on gnomAD, which I think provides significant evidence that they might not be pathogenic for a severe autosomal recessive condition. Most notably, 1 of the variants (i.e. I668F), which the authors promote as a pathogenic Ashkenazi Jewish founder variant (but which is also fairly frequent in non-Finnish Europeans) is detected in 7 homozygotes on gnomAD and was found to have ~80% loss of PLD1 function in their assay. This suggests that significant loss of function of this gene (i.e. down to 20%) might not be causative of a severe recessive condition (that is not to say that total or near total loss of function is not causative). Three other of the variants promoted as pathogenic in this article are also detected in homozygotes on gnomAD.

I think one of the major pieces of missing information required to make a full assessment of this gene’s linkage to disease is that is unknown how frequent biallelic (apparently loss of function) variant genotypes are in the general population or in healthy control individuals. Although homozygosity for any one variant can be determined from gnomAD, compound heterozygosity (which is likely to represent the vast majority of biallelic genotypes) cannot be assessed on gnomAD, and I can find no record in the literature of this being assessed in a normal control cohort. Without this information, we cannot know whether biallelic PLD1 genotypes are specific to babies with this severe phenotype. Without knowing this, and in the absence of any significant cosegregation data for any variant, there is no reasonable basis upon which one can conclude that this is a valid autosomal recessive gene for the phenotype. Without such validation, PVS1 cannot be applied for any apparent loss of function variant. Given this, and the general lack of cosegregation data for any one variant, I do not believe there is any PLD1 variant reported in the literature that could be classified as anything but uncertain significance (if not benign or likely benign) on the basis of current variant classification guidelines. Also, there are only two cases of biallelic variants in neonates where the primary phenotype is cardiomyopathy, and of these only one was dilated cardiomyopathy (the other was histiocytoid cardiomyopathy). Hence, the evidence linking this gene to cardiomyopathy is even weaker than it is for valvular defects. I, therefore, do not feel there is sufficient evidence to justify this gene being tested as part of the R135 paediatric cardiomyopathy gene panel.

Other papers (e.g. PMIDs: 33142350, 35380090, 36923242, 37770978) reporting a link between PLD1 genotypes and early onset cardiac disease (not cardiomyopathy) have been published. However, again, I do not think there is sufficient data in the articles to allow any of the variants detected to be confidently classified as anything but VUS according to current variant classification guidelines."
Created: 31 Jan 2024, 12:04 p.m. | Last Modified: 31 Jan 2024, 12:17 p.m
Paediatric or syndromic cardiomyopathy v3.46 PLD1 Arina Puzriakova Tag Q2_24_demote_red tag was added to gene: PLD1.
Tag Q2_24_expert_review tag was added to gene: PLD1.
Tag Q2_24_NHS_review tag was added to gene: PLD1.
Early onset or syndromic epilepsy v4.195 GLI3 Arina Puzriakova Mode of inheritance for gene: GLI3 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v4.194 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from to Greig cephalopolysyndactyly syndrome, OMIM:175700; Pallister-Hall syndrome, OMIM:146510
Skeletal ciliopathies v3.22 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Joubert Syndrome and Senior-Loken Syndrome 24 gene panel to Greig cephalopolysyndactyly syndrome, OMIM:175700; Pallister-Hall syndrome, OMIM:146510
Childhood onset dystonia, chorea or related movement disorder v3.76 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Joubert Syndrome and Senior-Loken Syndrome 24 gene panel to Greig cephalopolysyndactyly syndrome, OMIM:175700; Pallister-Hall syndrome, OMIM:146510
Neurological ciliopathies v3.19 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Joubert Syndrome and Senior-Loken Syndrome 24 gene panel to Greig cephalopolysyndactyly syndrome, OMIM:175700; Pallister-Hall syndrome, OMIM:146510
Ophthalmological ciliopathies v3.6 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Joubert Syndrome and Senior-Loken Syndrome 24 gene panel to Greig cephalopolysyndactyly syndrome, OMIM:175700; Pallister-Hall syndrome, OMIM:146510
Rare multisystem ciliopathy disorders v1.171 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Joubert Syndrome and Senior-Loken Syndrome 24 gene panel to Greig cephalopolysyndactyly syndrome, OMIM:175700; Pallister-Hall syndrome, OMIM:146510
Clefting v4.109 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Pallister-Hall syndrome, 146510 to Pallister-Hall syndrome, OMIM:146510
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.180 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Greig cephalopolysyndactyly syndrome 175700; 175700 to Greig cephalopolysyndactyly syndrome, OMIM:175700
Unexplained young onset end-stage renal disease v3.41 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Pallister-Hall syndrome; Pallister-Hall syndrome 146510 to Pallister-Hall syndrome, OMIM:146510
CAKUT v1.176 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Pallister-Hall syndrome to Pallister-Hall syndrome, OMIM:146510
Unexplained kidney failure in young people v1.119 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Pallister-Hall syndrome 146510 to Pallister-Hall syndrome, OMIM:146510
Fetal anomalies v3.156 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from PALLISTER-HALL SYNDROME; GREIG CEPHALOPOLYSYNDACTYLY SYNDROME; PREAXIAL POLYDACTYLY TYPE IV; POSTAXIAL POLYDACTYLY TYPE A to Greig cephalopolysyndactyly syndrome, OMIM:175700; Pallister-Hall syndrome, OMIM:146510; Polydactyly, postaxial, types A1 and B, OMIM:174200; Polydactyly, preaxial, type IV, OMIM:174700
Skeletal dysplasia v4.57 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Greig cephalopolysyndactyly syndrome 175700; Polydactyly, postaxial, types A1 and B 174200; Polydactyly, preaxial, type IV 174700; Pallister-Hall syndrome 146510; {Hypothalamic hamartomas, somatic} 241800 to Greig cephalopolysyndactyly syndrome, OMIM:175700; Pallister-Hall syndrome, OMIM:146510; Polydactyly, postaxial, types A1 and B, OMIM:174200; Polydactyly, preaxial, type IV, OMIM:174700
Limb disorders v4.19 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Greig cephalopolysyndactyly syndrome 175700; Pallister-Hall syndrome 146510; Polydactyly, postaxial, types A1 and B 174200; Polydactyly, preaxial, type IV 174700; {Hypothalamic hamartomas, somatic} 241800; Polydactyly to Greig cephalopolysyndactyly syndrome, OMIM:175700; Pallister-Hall syndrome, OMIM:146510; Polydactyly, postaxial, types A1 and B, OMIM:174200; Polydactyly, preaxial, type IV, OMIM:174700
Pituitary hormone deficiency v3.12 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Greig cephalopolysyndactyly syndrome (175700); Pallister-Hall syndrome (146510) to Greig cephalopolysyndactyly syndrome, OMIM:175700; Pallister-Hall syndrome, OMIM:146510
Intellectual disability v5.535 GLI3 Arina Puzriakova Tag Q2_24_demote_amber tag was added to gene: GLI3.
Tag Q2_24_NHS_review tag was added to gene: GLI3.
Intellectual disability v5.535 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Greig cephalopolysyndactyly syndrome, 175700Pallister-Hall syndrome, 146510Polydactyly, preaxial, type IV, 174700Polydactyly, postaxial, types A1 and B, 174200{Hypothalamic hamartomas, somatic}, 241800; GREIG CEPHALOPOLYSYNDACTYLY SYNDROME to Greig cephalopolysyndactyly syndrome, OMIM:175700; Pallister-Hall syndrome, OMIM:146510
Intellectual disability v5.534 GLI3 Arina Puzriakova Publications for gene: GLI3 were set to
Intellectual disability v5.533 GLI3 Arina Puzriakova Classified gene: GLI3 as Green List (high evidence)
Intellectual disability v5.533 GLI3 Arina Puzriakova Added comment: Comment on list classification: Reassessed in view of the Red review by Tracy Lester on this Green gene

Rarely, individuals with Greig cephalopolysyndactyly syndrome or GLI3-Related Pallister-Hall syndrome have been found to have intellectual disability (PMID: 12414818; 14708104; 14608643; 34296525). This is usually observed in the most severely affected individuals and those with large deletions encompassing GLI3. The majority of patients have normal psychomotor development or only some mild delays. All GLI3-related disorders are more likely to be recognised in context of other features such as skeletal abnormalities.

Overall, I therefore agree that this gene could be demoted to Amber at the next GMS panel update.
Intellectual disability v5.533 GLI3 Arina Puzriakova Gene: gli3 has been classified as Green List (High Evidence).
Pigmentary skin disorders v3.11 BLM Dmitrijs Rots gene: BLM was added
gene: BLM was added to Pigmentary skin disorders. Sources: Expert Review
Mode of inheritance for gene: BLM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BLM were set to PMID: 32972601
Phenotypes for gene: BLM were set to Bloom syndrome
Penetrance for gene: BLM were set to Complete
Review for gene: BLM was set to GREEN
Added comment: Included in the review PMID: 32972601 as differential for cafe-au-lait
Sources: Expert Review
Pigmentary skin disorders v3.11 SMARCB1 Dmitrijs Rots gene: SMARCB1 was added
gene: SMARCB1 was added to Pigmentary skin disorders. Sources: Expert Review
Mode of inheritance for gene: SMARCB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMARCB1 were set to PMID: 32972601
Phenotypes for gene: SMARCB1 were set to Schwannomatosis-1, susceptibility to
Penetrance for gene: SMARCB1 were set to Incomplete
Review for gene: SMARCB1 was set to GREEN
Added comment: Included in the review PMID: 32972601 as differential for cafe-au-lait
Sources: Expert Review
Intellectual disability v5.532 CPA6 Arina Puzriakova Tag refuted tag was added to gene: CPA6.
Intellectual disability v5.532 CPA6 Arina Puzriakova commented on gene: CPA6
Severe microcephaly v4.67 SASS6 Zornitza Stark edited their review of gene: SASS6: Added comment: Two additional families:

PMID: 38501757
1x compound het for a fs and +3 splice variant.

Using cDNA RT-ed from mother's RNA, exons 13-15 were amplified and exon 14 was found to be skipped resulting in c.1546_1674del and p.516_558del

PMID: 36739862
1x family, compound het for 2 missense
Functional studies not performed; Changed rating: GREEN; Changed publications to: 24951542, 30639237, 38501757, 36739862
Intellectual disability v5.532 KCNB2 Zornitza Stark gene: KCNB2 was added
gene: KCNB2 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: KCNB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNB2 were set to 38503299
Phenotypes for gene: KCNB2 were set to neurodevelopmental disorder MONDO:0700092, KCNB2-related
Review for gene: KCNB2 was set to GREEN
Added comment: 7 individuals, all missense
5 de novo + 1x inherited from father who has hypotonia + 1x from asymptomatic father

2/5 MRI anomalies
2/5 cardiac anomalies
2/7 urogenital anomalies
7/7 with ID
2/7 epilepsy
2/7 hypotonia
Sources: Literature
Intellectual disability v5.532 GTF3C5 Zornitza Stark gene: GTF3C5 was added
gene: GTF3C5 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: GTF3C5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTF3C5 were set to 38520561; 35503477
Phenotypes for gene: GTF3C5 were set to neurodevelopmental disorder MONDO:0700092, GTF3C5-related
Review for gene: GTF3C5 was set to GREEN
Added comment: 4 families/probands with syndromic ID. Loss of function is the expected mechanism.
PMID: 38520561 - Biallelic variants identified (3 missense & 1 stopgain) in 4 individuals from 3 families presenting with multisystem developmental syndrome including the features: growth retardation, developmental delay, intellectual disability, dental anomalies, cerebellar malformations, delayed bone age, skeletal anomalies, and facial dysmorphism. Gene-disease relationship supported by: reduced protein expression in patient cells, yeast assays, and a zebrafish model
PMID: 35503477 - 1 proband with biallelic missense variants and hypomelanosis of Ito, seizures, growth retardation, abnormal brain MRI, developmental delay, and facial dysmorphism
Sources: Literature
Intellectual disability v5.532 DOCK4 Zornitza Stark gene: DOCK4 was added
gene: DOCK4 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: DOCK4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DOCK4 were set to 38526744
Phenotypes for gene: DOCK4 were set to DOCK4-related neurodevelopmental disorder (MONDO:0060490)
Review for gene: DOCK4 was set to GREEN
Added comment: 7 unrelated individuals reported with heterozygous variants (missense or null variants) in DOCK4. The individuals either had ID or DD between mild and moderate with brain abnormalities. Two of the individuals are reportedly compound heterozygous.

Functional assay neuro-2A Dock4 knockout cells by using the Alt-R CRISPR-Cas9 system utilizing two different guide RNAs (ko1 and ko2) and one nonspecific control guide RNA (C: control). The assay depicted the loss of function mechanism in the presence of either p.Arg853Leu and p.Asp946_Lys1966delinsValSer* (described as 945VS).
Sources: Literature
Intellectual disability v5.532 PLXNB2 Zornitza Stark gene: PLXNB2 was added
gene: PLXNB2 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: PLXNB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLXNB2 were set to 38458752
Phenotypes for gene: PLXNB2 were set to Syndromic disease MONDO:0002254, PLXNB2 -related
Review for gene: PLXNB2 was set to GREEN
Added comment: 8 individuals from 6 families with core features of amelogenesis imperfecta and sensorineural hearing loss. Intellectual disability, ocular disease, ear developmental abnormalities and lymphoedema were also present in multiple cases. WES and WGS identified biallelic pathogenic variants in PLXNB2 (missense, nonsense, splice and a multiexon deletion variants). Variants segregated with disease.

PLXNB2 is a large transmembrane semaphorin receptor protein, and semaphorin-plexin signalling controls cellular interactions that are critical during development as well as in adult life stages. Plxnb2 expression was detected in differentiating ameloblasts in mice. Human phenotype overlaps with that seen in Plxnb2 knockout mice.
Sources: Literature
Monogenic hearing loss v4.38 KIAA1024L Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: KIAA1024L.
Monogenic hearing loss v4.38 KIAA1024L Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient evidence available for the association of this gene to green rating in the next GMS review.; to: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Monogenic hearing loss v4.38 KIAA1024L Achchuthan Shanmugasundram Classified gene: KIAA1024L as Amber List (moderate evidence)
Monogenic hearing loss v4.38 KIAA1024L Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the association of this gene to green rating in the next GMS review.
Monogenic hearing loss v4.38 KIAA1024L Achchuthan Shanmugasundram Gene: kiaa1024l has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v4.37 KIAA1024L Achchuthan Shanmugasundram commented on gene: KIAA1024L: The new gene name for KIAA1024L is MINAR2 and 'new-gene-name' tag has been added to flag this.
Monogenic hearing loss v4.37 KIAA1024L Achchuthan Shanmugasundram gene: KIAA1024L was added
gene: KIAA1024L was added to Monogenic hearing loss. Sources: Literature
new-gene-name tags were added to gene: KIAA1024L.
Mode of inheritance for gene: KIAA1024L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIAA1024L were set to 35727972
Phenotypes for gene: KIAA1024L were set to Deafness, autosomal recessive 120, OMIM:620238
Review for gene: KIAA1024L was set to GREEN
Added comment: PMID:35727972 reported 13 patients from four unrelated families with non-syndromic sensorineural hearing loss. Four of these patients had prelingual onset of severe to profound, progressive bilateral hearing loss. The other nine patients had congenital onset of severe to profound bilateral hearing loss, which was not progressive on one patient, while data was not available for the other.

Three different homozygous variants (c.144G > A/ p.Trp48Ter, c.412_419delCGGTTTTG/ p.Arg138Valfs*10 and c.393G > T/ p.Lys131Asn) were identified in MINAR2/ KIAA1024L gene in these patients.

There is some functional evidence available for the p.Lys131Asn variant. In addition, mice with loss of function of the Minar2 protein present with rapidly progressive sensorineural hearing loss.

This gene has also been associated with relevant phenotype in OMIM (MIM #620238).
Sources: Literature
Intellectual disability v5.532 CEP295 Zornitza Stark edited their review of gene: CEP295: Changed rating: GREEN
Intellectual disability v5.532 CEP295 Zornitza Stark gene: CEP295 was added
gene: CEP295 was added to Intellectual disability - microarray and sequencing. Sources: Expert Review
Mode of inheritance for gene: CEP295 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP295 were set to 38154379
Phenotypes for gene: CEP295 were set to Seckel syndrome 11, OMIM # 620767
Added comment: 4 children from 2 unrelated families with Seckel-like syndrome - severe primary microcephaly, short stature, developmental delay, intellectual disability, facial deformities, and abnormalities of fingers and toes. WES identified biallelic pathogenic variants in CEP295 gene (p(Q544∗) and p(R1520∗); p(R55Efs∗49) and p(P562L)).

Patient-derived fibroblasts and CEP295-depleted U2OS and RPE1 cells were used to clarify the underlying mechanisms. Depletion of CEP295 resulted in a decrease in the numbers of centrioles and centrosomes and triggered p53-dependent G1 cell cycle arrest. Loss of CEP295 caused extensive primary ciliary defects in both patient-derived fibroblasts and RPE1 cells. The results from complementary experiments revealed that the wild-type CEP295, but not the mutant protein, can correct the developmental defects of the centrosome/centriole and cilia in the patient-derived skin fibroblasts.
Sources: Expert Review
Ataxia and cerebellar anomalies - narrow panel v4.63 ATP2B3 Achchuthan Shanmugasundram Classified gene: ATP2B3 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v4.63 ATP2B3 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.
Ataxia and cerebellar anomalies - narrow panel v4.63 ATP2B3 Achchuthan Shanmugasundram Gene: atp2b3 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v4.62 ATP2B3 Achchuthan Shanmugasundram Publications for gene: ATP2B3 were set to
Ataxia and cerebellar anomalies - narrow panel v4.61 ATP2B3 Achchuthan Shanmugasundram Phenotypes for gene: ATP2B3 were changed from Spinocerebellar ataxia, X-linked 1 to ?Spinocerebellar ataxia, X-linked 1, OMIM:302500
Ataxia and cerebellar anomalies - narrow panel v4.60 ATP2B3 Achchuthan Shanmugasundram Mode of inheritance for gene: ATP2B3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Ataxia and cerebellar anomalies - narrow panel v4.59 ATP2B3 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: ATP2B3.
Ataxia and cerebellar anomalies - narrow panel v4.59 ATP2B3 Achchuthan Shanmugasundram changed review comment from: There are six unrelated cases reported with X-linked recessive variants in ATP2B3 gene and with a phenotype comprising ataxia. However, the onset of the disease was during childhood in three of these cases, while detailed clinical information was not available for the other three cases. There is also functional evidence available.

This gene has already been associated with ataxia in OMIM (MIM #302500), but not yet with any phenotypes in Gene2Phenotype.; to: There are six unrelated cases reported with five different X-linked recessive variants in ATP2B3 gene and with a phenotype comprising ataxia. However, the onset of the disease was during childhood in three of these cases, while detailed clinical information was not available for the other three cases. There is also functional evidence available.

This gene has already been associated with ataxia in OMIM (MIM #302500), but not yet with any phenotypes in Gene2Phenotype.
Ataxia and cerebellar anomalies - narrow panel v4.59 ATP2B3 Achchuthan Shanmugasundram reviewed gene: ATP2B3: Rating: GREEN; Mode of pathogenicity: None; Publications: 25953895, 28807751, 36207321; Phenotypes: ?Spinocerebellar ataxia, X-linked 1, OMIM:302500; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Hereditary ataxia with onset in adulthood v4.34 ATP2B3 Achchuthan Shanmugasundram changed review comment from: There are six unrelated cases reported with X-linked recessive variants in ATP2B3 gene and with a phenotype comprising ataxia. However, the onset of the disease was during childhood inn three of these cases, while detailed clinical information was not available for the other three cases.; to: There are six unrelated cases reported with X-linked recessive variants in ATP2B3 gene and with a phenotype comprising ataxia. However, the onset of the disease was during childhood in three of these cases, while detailed clinical information was not available for the other three cases.
Hereditary ataxia with onset in adulthood v4.34 ATP2B3 Achchuthan Shanmugasundram Phenotypes for gene: ATP2B3 were changed from Spinocerebellar ataxia, X-linked 1; X-linked spinocerebellar ataxia, 302500 to ?Spinocerebellar ataxia, X-linked 1, OMIM:302500
Hereditary ataxia with onset in adulthood v4.33 ATP2B3 Achchuthan Shanmugasundram Publications for gene: ATP2B3 were set to
Hereditary ataxia with onset in adulthood v4.32 ATP2B3 Achchuthan Shanmugasundram Mode of inheritance for gene: ATP2B3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Hereditary ataxia with onset in adulthood v4.31 ATP2B3 Achchuthan Shanmugasundram commented on gene: ATP2B3: There are six unrelated cases reported with X-linked recessive variants in ATP2B3 gene and with a phenotype comprising ataxia. However, the onset of the disease was during childhood inn three of these cases, while detailed clinical information was not available for the other three cases.
Hereditary ataxia with onset in adulthood v4.31 ATP2B3 Achchuthan Shanmugasundram edited their review of gene: ATP2B3: Changed phenotypes to: ?Spinocerebellar ataxia, X-linked 1, OMIM:302500
Hereditary ataxia with onset in adulthood v4.31 ATP2B3 Achchuthan Shanmugasundram reviewed gene: ATP2B3: Rating: AMBER; Mode of pathogenicity: None; Publications: 25953895, 28807751, 36207321; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.532 SMAD3 Achchuthan Shanmugasundram changed review comment from: Two out of six cases with single nucleotide variants from DECIPHER database (https://www.deciphergenomics.org/gene/SMAD3/patient-overlap/snvs )were reported with global developmental delay. However, intellectual disability or global developmental delay were not reported as clinical presentations in patients with Loeys-Dietz syndrome 3 (MIM #613795).; to: Two out of six cases with single nucleotide variants from DECIPHER database (https://www.deciphergenomics.org/gene/SMAD3/patient-overlap/snvs) were reported with global developmental delay. However, intellectual disability or global developmental delay were not reported as clinical presentations in patients with Loeys-Dietz syndrome 3 (MIM #613795). Hence the rating should remain amber with current evidence.
Intellectual disability v5.532 SMAD3 Achchuthan Shanmugasundram reviewed gene: SMAD3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Neurological segmental overgrowth v2.12 MAX Achchuthan Shanmugasundram Classified gene: MAX as Amber List (moderate evidence)
Neurological segmental overgrowth v2.12 MAX Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by James Poulter, there is sufficient evidence available (three unrelated cases with the same p.Arg60Gln variant and functional studies) for the promotion of this gene to green rating in the next GMS update.
Neurological segmental overgrowth v2.12 MAX Achchuthan Shanmugasundram Gene: max has been classified as Amber List (Moderate Evidence).
Neurological segmental overgrowth v2.11 MAX Achchuthan Shanmugasundram changed review comment from: PMID:38141607 reported three individuals with the same recurrent de novo germline variant in the MAX gene (p.Arg60Gln). Affected individuals have a complex disorder consisting primarily of macrocephaly, polydactyly, and delayed ophthalmic development. Other phenotypes reported include intellectual disability, perianal abscesses, pectus carinatum, hypospadias, renal agenesis, single umbilical artery, flattened thoracic vertebrae.

Functional analysis of the p.Arg60Gln variant shows a significant increase in CCND2 protein and a more efficient heterodimerization with c-Myc resulting in an increase in transcriptional activity of c-Myc.; to: PMID:38141607 reported three individuals with the same recurrent de novo germline variant in the MAX gene (p.Arg60Gln). Affected individuals have a complex disorder consisting primarily of macrocephaly, polydactyly, and delayed ophthalmic development. Other phenotypes reported include intellectual disability, perianal abscesses, pectus carinatum, hypospadias, renal agenesis, single umbilical artery, flattened thoracic vertebrae.

Functional analysis of the p.Arg60Gln variant shows a significant increase in CCND2 protein and a more efficient heterodimerization with c-Myc resulting in an increase in transcriptional activity of c-Myc.

This gene has been associated with relevant phenotypes in OMIM (MIM #620712).
Neurological segmental overgrowth v2.11 MAX Achchuthan Shanmugasundram Phenotypes for gene: MAX were changed from Macrocephaly; Polydactyly; delayed ophthalmic development; autism to Polydactyly-macrocephaly syndrome, OMIM:620712
Neurological segmental overgrowth v2.10 MAX Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: MAX.
Tag Q2_24_NHS_review tag was added to gene: MAX.
Neurological segmental overgrowth v2.10 MAX Achchuthan Shanmugasundram changed review comment from: Three individuals who each share a recurrent de novo germline variant in the MAX gene, resulting in a p.Arg60Gln substitution in the loop of the b-HLH-LZ domain.

Affected individuals have a complex disorder consisting primarily of macrocephaly, polydactyly, and delayed ophthalmic development. Other phenotypes reported include intellectual disability, perianal abscesses, pectus carinatum, hypospadias, renal agenesis, single umbilical artery, flattened thoracic vertebrae.

Functional analysis of the p.Arg60Gln variant shows a significant increase in CCND2 protein and a more efficient heterodimerization with c-Myc resulting in an increase in transcriptional activity of c-Myc.; to: PMID:38141607 reported three individuals with the same recurrent de novo germline variant in the MAX gene (p.Arg60Gln). Affected individuals have a complex disorder consisting primarily of macrocephaly, polydactyly, and delayed ophthalmic development. Other phenotypes reported include intellectual disability, perianal abscesses, pectus carinatum, hypospadias, renal agenesis, single umbilical artery, flattened thoracic vertebrae.

Functional analysis of the p.Arg60Gln variant shows a significant increase in CCND2 protein and a more efficient heterodimerization with c-Myc resulting in an increase in transcriptional activity of c-Myc.
Neurological segmental overgrowth v2.10 MAX Achchuthan Shanmugasundram Publications for gene: MAX were set to PMID:38141607
Neurological segmental overgrowth v2.9 MAX Achchuthan Shanmugasundram commented on gene: MAX: Three individuals who each share a recurrent de novo germline variant in the MAX gene, resulting in a p.Arg60Gln substitution in the loop of the b-HLH-LZ domain.

Affected individuals have a complex disorder consisting primarily of macrocephaly, polydactyly, and delayed ophthalmic development. Other phenotypes reported include intellectual disability, perianal abscesses, pectus carinatum, hypospadias, renal agenesis, single umbilical artery, flattened thoracic vertebrae.

Functional analysis of the p.Arg60Gln variant shows a significant increase in CCND2 protein and a more efficient heterodimerization with c-Myc resulting in an increase in transcriptional activity of c-Myc.
Neurological segmental overgrowth v2.9 MAX Achchuthan Shanmugasundram reviewed gene: MAX: Rating: GREEN; Mode of pathogenicity: None; Publications: 38141607; Phenotypes: Polydactyly-macrocephaly syndrome, OMIM:620712; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.532 ZFX Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene has now been associated with phenotype in OMIM (MIM #301118), but not yet in Gene2Phenotype.
Intellectual disability v5.532 ZFX Achchuthan Shanmugasundram Phenotypes for gene: ZFX were changed from X-linked neurodevelopmental disorder with recurrent facial gestalt to Intellectual developmental disorder, X-linked syndromic 37, OMIM:301118
Hereditary neuropathy or pain disorder v3.94 CADM3 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Ian Berry, there are now five unrelated families with peripheral neuropathy and with one of the two reported missense variants in heterozygous state. Hence, this gene can be promoted to green rating in the next GMS update.; to: Comment on list classification: As reviewed by Ian Berry, there are now at least nine probands with peripheral neuropathy and with one of the two reported missense variants in heterozygous state. Hence, this gene can be promoted to green rating in the next GMS update.
Hereditary neuropathy or pain disorder v3.94 CADM3 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: CADM3.
Tag Q2_24_NHS_review tag was added to gene: CADM3.
Hereditary neuropathy or pain disorder v3.94 CADM3 Achchuthan Shanmugasundram Classified gene: CADM3 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v3.94 CADM3 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Ian Berry, there are now five unrelated families with peripheral neuropathy and with one of the two reported missense variants in heterozygous state. Hence, this gene can be promoted to green rating in the next GMS update.
Hereditary neuropathy or pain disorder v3.94 CADM3 Achchuthan Shanmugasundram Gene: cadm3 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v3.93 CADM3 Achchuthan Shanmugasundram Publications for gene: CADM3 were set to 33889941
Hereditary neuropathy or pain disorder v3.92 CADM3 Achchuthan Shanmugasundram reviewed gene: CADM3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Monogenic hearing loss v4.36 GRXCR2 Sadaf Naz reviewed gene: GRXCR2: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 33528103, PMID:24619944; Phenotypes: #615837: Deafness, autosomal recessive 101; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Paediatric or syndromic cardiomyopathy v3.46 CASZ1 Achchuthan Shanmugasundram Classified gene: CASZ1 as Amber List (moderate evidence)
Paediatric or syndromic cardiomyopathy v3.46 CASZ1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Ludmila Volozonoka, there is sufficient evidence available (three unrelated cases and some functional studies) for the promotion of this gene to green rating in the next GMS update.
Paediatric or syndromic cardiomyopathy v3.46 CASZ1 Achchuthan Shanmugasundram Gene: casz1 has been classified as Amber List (Moderate Evidence).
Paediatric or syndromic cardiomyopathy v3.45 CASZ1 Achchuthan Shanmugasundram Phenotypes for gene: CASZ1 were changed from Pediatric Dilated Cardiomyopathy; Pediatric LVNC to dilated cardiomyopathy, MONDO:0005021; left ventricular noncompaction, MONDO:0018901
Paediatric or syndromic cardiomyopathy v3.44 CASZ1 Achchuthan Shanmugasundram changed review comment from: PMID:28099117 reported a patient with a novel heterozygous CASZ1 variant (p.K351X) and with dilated cardiomyopathy (DCM). The variant co-segregated with DCM, which was transmitted in an autosomal dominant pattern with complete penetrance. The functional characterisation of the variant with a luciferase reporter assay showed that the variant had no transcriptional activity.

PMID:31268246 reported the identification of a previously unreported de novo heterozygous frameshift variant (p.Val815Profs*14) in CASZ1 in an 11-month-old Chinese boy with DCM and left ventricular noncompaction cardiomyopathy (LVNC).

PMID:36293425 reported a girl with a new de novo frameshift variant (p.Trp1261GlyfsTer29) in CASZ1 gene. DCM was diagnosed for the first time at the age of three months and she died at the age of 1 year 10 months with a diagnosis of dilated cardiomyopathy and decompensation, systemic multiple organ failure, post-anoxic brain damage and gastrointestinal and vaginal bleeding.; to: PMID:28099117 reported a patient with a novel heterozygous CASZ1 variant (p.K351X) and with dilated cardiomyopathy (DCM). The variant co-segregated with DCM, which was transmitted in an autosomal dominant pattern with complete penetrance. The functional characterisation of the variant with a luciferase reporter assay showed that the variant had no transcriptional activity.

PMID:31268246 reported the identification of a previously unreported de novo heterozygous frameshift variant (p.Val815Profs*14) in CASZ1 in an 11-month-old Chinese boy with DCM and left ventricular noncompaction cardiomyopathy (LVNC).

PMID:36293425 reported a girl with a new de novo frameshift variant (p.Trp1261GlyfsTer29) in CASZ1 gene. DCM was diagnosed for the first time at the age of three months and she died at the age of 1 year 10 months with a diagnosis of dilated cardiomyopathy and decompensation, systemic multiple organ failure, post-anoxic brain damage and gastrointestinal and vaginal bleeding.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Paediatric or syndromic cardiomyopathy v3.44 CASZ1 Achchuthan Shanmugasundram edited their review of gene: CASZ1: Changed phenotypes to: dilated cardiomyopathy, MONDO:0005021, left ventricular noncompaction, MONDO:0018901
Paediatric or syndromic cardiomyopathy v3.44 CASZ1 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: CASZ1.
Paediatric or syndromic cardiomyopathy v3.44 CASZ1 Achchuthan Shanmugasundram reviewed gene: CASZ1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28099117, 31268246, 36293425; Phenotypes: dilated cardiomyopathy, MONDO:0005021; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Retinal disorders v4.89 MT-ATP6 Achchuthan Shanmugasundram Tag Q2_24_NHS_review tag was added to gene: MT-ATP6.
Retinal disorders v4.89 SLC37A3 Achchuthan Shanmugasundram Tag Q2_24_NHS_review tag was added to gene: SLC37A3.
Retinal disorders v4.89 SLC37A3 Achchuthan Shanmugasundram Classified gene: SLC37A3 as Amber List (moderate evidence)
Retinal disorders v4.89 SLC37A3 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Siying Lin, there is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.
Retinal disorders v4.89 SLC37A3 Achchuthan Shanmugasundram Gene: slc37a3 has been classified as Amber List (Moderate Evidence).
Retinal disorders v4.88 SLC37A3 Achchuthan Shanmugasundram Phenotypes for gene: SLC37A3 were changed from Retinitis pigmentosa; No OMIM entry to retinitis pigmentosa, MONDO:0019200
Retinal disorders v4.87 SLC37A3 Achchuthan Shanmugasundram Publications for gene: SLC37A3 were set to 28041643
Retinal disorders v4.86 SLC37A3 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: SLC37A3.
Retinal disorders v4.86 SLC37A3 Achchuthan Shanmugasundram reviewed gene: SLC37A3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: retinitis pigmentosa, MONDO:0019200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v4.86 MT-ATP6 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: MT-ATP6.
Retinal disorders v4.86 MT-ATP6 Achchuthan Shanmugasundram Classified gene: MT-ATP6 as Amber List (moderate evidence)
Retinal disorders v4.86 MT-ATP6 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is ample evidence available for the association of MT-ATP6 gene with retinitis pigmentosa. Hence, this gene can be promoted to green rating in the next GMS review.
Retinal disorders v4.86 MT-ATP6 Achchuthan Shanmugasundram Gene: mt-atp6 has been classified as Amber List (Moderate Evidence).
Retinal disorders v4.85 MT-ATP6 Achchuthan Shanmugasundram Phenotypes for gene: MT-ATP6 were changed from Retinitis pigmentosa to NARP syndrome, MONDO:0010794
Retinal disorders v4.84 MT-ATP6 Achchuthan Shanmugasundram Publications for gene: MT-ATP6 were set to
Retinal disorders v4.83 MT-ATP6 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: MT-ATP6.
Retinal disorders v4.83 MT-ATP6 Achchuthan Shanmugasundram reviewed gene: MT-ATP6: Rating: GREEN; Mode of pathogenicity: None; Publications: 11843698, 17568559, 19124644, 22819295, 23266623, 24118886, 27015314, 29054413, 29224958, 36809201; Phenotypes: NARP syndrome, MONDO:0010794; Mode of inheritance: MITOCHONDRIAL
Primary immunodeficiency or monogenic inflammatory bowel disease v4.201 PTCRA Achchuthan Shanmugasundram Classified gene: PTCRA as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.201 PTCRA Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.201 PTCRA Achchuthan Shanmugasundram Gene: ptcra has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.200 PTCRA Achchuthan Shanmugasundram Phenotypes for gene: PTCRA were changed from Autoimmunity; elevated TCRgamma/delta T cells; lymphopenia; low TREC to Autoimmunity, HP:0002960; lymphopenia, MONDO:0003783
Primary immunodeficiency or monogenic inflammatory bowel disease v4.199 PTCRA Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: PTCRA.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.199 PTCRA Achchuthan Shanmugasundram reviewed gene: PTCRA: Rating: GREEN; Mode of pathogenicity: None; Publications: 38422122; Phenotypes: Autoimmunity, HP:0002960, lymphopenia, MONDO:0003783; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v3.92 GAN Arina Puzriakova Publications for gene: GAN were set to 1106248
Hereditary neuropathy or pain disorder v3.91 GAN Arina Puzriakova Classified gene: GAN as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v3.91 GAN Arina Puzriakova Added comment: Comment on list classification: This gene should be promoted to Green at the next GMS panel update as the scope of this panel has now been expanded to include complex cases of neuropathy.
Biallelic variants in the GAN gene cause giant axonal neuropathy. This childhood onset polyneuropathy results in progressive neurodegeneration of both the peripheral and central nervous systems. More than 10 unrelated cases have been reported in the literature which is sufficient for making this gene Green (PMIDs: 18595793; 19231187; 20949505; 27852232; 36866531)
Hereditary neuropathy or pain disorder v3.91 GAN Arina Puzriakova Gene: gan has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.531 GAN Arina Puzriakova changed review comment from: Comment on list classification: Biallelic variants in the GAN gene cause giant axonal neuropathy, characterised by abnormalities in the peripheral and central nervous systems. Though extent of CNS involvement can vary, intellectual disability has been reported in at least 3 unrelated cases to date (PMID: 18595793; 19231187). Therefore, this gene should be promoted to Green at the next GMS panel update.; to: Comment on list classification: Biallelic variants in the GAN gene cause giant axonal neuropathy, characterised by abnormalities in the peripheral and central nervous systems. Though extent of CNS involvement can vary, intellectual disability has been reported in at least 3 unrelated cases (PMID: 18595793; 19231187). Therefore, this gene should be promoted to Green at the next GMS panel update.
Intellectual disability v5.531 GAN Arina Puzriakova Tag Q2_24_promote_green tag was added to gene: GAN.
Tag Q2_24_NHS_review tag was added to gene: GAN.
Intellectual disability v5.531 GAN Arina Puzriakova Publications for gene: GAN were set to
Intellectual disability v5.530 GAN Arina Puzriakova Classified gene: GAN as Amber List (moderate evidence)
Intellectual disability v5.530 GAN Arina Puzriakova Added comment: Comment on list classification: Biallelic variants in the GAN gene cause giant axonal neuropathy, characterised by abnormalities in the peripheral and central nervous systems. Though extent of CNS involvement can vary, intellectual disability has been reported in at least 3 unrelated cases to date (PMID: 18595793; 19231187). Therefore, this gene should be promoted to Green at the next GMS panel update.
Intellectual disability v5.530 GAN Arina Puzriakova Gene: gan has been classified as Amber List (Moderate Evidence).
Arthrogryposis v5.22 COASY Hannah Knight reviewed gene: COASY: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 35499143; Phenotypes: Pontocerebellar hypoplasia type 12; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v5.22 PIP5K1C Hannah Knight reviewed gene: PIP5K1C: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 38491417; Phenotypes: Lethal congenital contractural syndrome 3 611369; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v3.90 GAN Arina Puzriakova Tag Q2_24_promote_green tag was added to gene: GAN.
Tag Q2_24_NHS_review tag was added to gene: GAN.
Arthrogryposis v5.22 SLC18A3 Hannah Knight reviewed gene: SLC18A3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34943989; Phenotypes: Myasthenic syndrome, congenital, 21, presynaptic; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v5.22 TRIP4 Hannah Knight reviewed gene: TRIP4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31794073; Phenotypes: Spinal muscular atrophy with congenital bone fractures 1; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.529 GAN Arina Puzriakova Mode of inheritance for gene: GAN was changed from to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.528 GAN Arina Puzriakova Phenotypes for gene: GAN were changed from to Giant axonal neuropathy-1, OMIM:256850
Hereditary neuropathy v1.477 GAN Arina Puzriakova Phenotypes for gene: GAN were changed from Giant axonal neuropathy-1 to Giant axonal neuropathy-1, OMIM:256850
Hereditary neuropathy or pain disorder v3.90 GAN Arina Puzriakova Phenotypes for gene: GAN were changed from Giant axonal neuropathy-1 to Giant axonal neuropathy-1, OMIM:256850
Intellectual disability v5.527 SEPHS1 Arina Puzriakova Classified gene: SEPHS1 as Amber List (moderate evidence)
Intellectual disability v5.527 SEPHS1 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update.
Intellectual disability v5.527 SEPHS1 Arina Puzriakova Gene: sephs1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.526 SEPHS1 Arina Puzriakova Classified gene: SEPHS1 as Amber List (moderate evidence)
Intellectual disability v5.526 SEPHS1 Arina Puzriakova Gene: sephs1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.525 SEPHS1 Arina Puzriakova gene: SEPHS1 was added
gene: SEPHS1 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Q2_24_promote_green tags were added to gene: SEPHS1.
Mode of inheritance for gene: SEPHS1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SEPHS1 were set to 38531365
Phenotypes for gene: SEPHS1 were set to Neurodevelopmental disorder, MONDO:0700092
Review for gene: SEPHS1 was set to GREEN
Added comment: Mullegama et al. (2024) reported 9 individuals from 8 families with developmental delay, growth and feeding problems, hypotonia, and dysmorphic features, all with heterozygous missense variants in SEPHS1. Eight individuals shared different missense variants at the same p.Arg371 residue in SEPHS1 (p.Arg371Trp, p.Arg371Gln, and p.Arg371Gly); seven of these variants were confirmed as de novo (one unknown). Functional studies showed that variants at the Arg371 residue impact direct protein-protein interactions of SEPSH1 and enhance cell proliferation by modulating ROS homeostasis.
Sources: Literature
Fetal anomalies v3.155 GRM1 Arina Puzriakova Classified gene: GRM1 as Red List (low evidence)
Fetal anomalies v3.155 GRM1 Arina Puzriakova Added comment: Comment on list classification: Demoted from Amber to Red inline with review by Zornitza Stark. Could not find any evidence of prenatal phenotypes in patients with GRM1 variants.
Fetal anomalies v3.155 GRM1 Arina Puzriakova Gene: grm1 has been classified as Red List (Low Evidence).
Stickler syndrome v4.4 LRP2 Arina Puzriakova Classified gene: LRP2 as Red List (low evidence)
Stickler syndrome v4.4 LRP2 Arina Puzriakova Added comment: Comment on list classification: Demoted from Amber to Red inline with review by Dmitrijs Rots.

Only a single family reported with features overlapping those of Stickler syndrome (PMID:23992033), mainly based on their ocular phenotype, including high myopia, vitreous changes, cataract and esotropia. LRP2 variants are typically associated with Donnai-Barrow syndrome and facio-oculo-acoustico-renal syndrome which are not relevant to this panel.
Stickler syndrome v4.4 LRP2 Arina Puzriakova Gene: lrp2 has been classified as Red List (Low Evidence).
Cytopenia - NOT Fanconi anaemia v3.32 FCGR3B Arina Puzriakova Classified gene: FCGR3B as Red List (low evidence)
Cytopenia - NOT Fanconi anaemia v3.32 FCGR3B Arina Puzriakova Added comment: Comment on list classification: Demoted from Amber to Red inline with review by Dmitrijs Rots.

Also note review from Helen Brittain (Genomics England Clinical Team) on 100K panel Cytopenias and congenital anaemias (159) from 9 Mar 2017:

"Relevant phenotype affects neutrophils only, on a transient basis owing to presence of antibodies in mother and antigen in fetus (as a result of different genetic factors in father and mother.). Therefore not a germline condition associated with mutations in the child."
Cytopenia - NOT Fanconi anaemia v3.32 FCGR3B Arina Puzriakova Gene: fcgr3b has been classified as Red List (Low Evidence).
Rare genetic inflammatory skin disorders v3.19 ADAMTS2 Arina Puzriakova Classified gene: ADAMTS2 as Red List (low evidence)
Rare genetic inflammatory skin disorders v3.19 ADAMTS2 Arina Puzriakova Added comment: Comment on list classification: Demoted from Amber to Red inline with review by Dmitrijs Rots.
Rare genetic inflammatory skin disorders v3.19 ADAMTS2 Arina Puzriakova Gene: adamts2 has been classified as Red List (Low Evidence).
Dilated and arrhythmogenic cardiomyopathy v2.22 MYZAP Arina Puzriakova Tag Q2_24_promote_green tag was added to gene: MYZAP.
Dilated and arrhythmogenic cardiomyopathy v2.22 MYZAP Arina Puzriakova Deleted their comment
Dilated and arrhythmogenic cardiomyopathy v2.22 MYZAP Arina Puzriakova Publications for gene: MYZAP were set to 34899865; 20093627; 35840178
Dilated and arrhythmogenic cardiomyopathy v2.21 MYZAP Arina Puzriakova Classified gene: MYZAP as Amber List (moderate evidence)
Dilated and arrhythmogenic cardiomyopathy v2.21 MYZAP Arina Puzriakova Added comment: Comment on list classification: New gene added to the panel by Aleš Maver. MYZAP is not yet associated with any phenotype in OMIM or Gene2Phenoype. At least three unrelated families have been reported with biallelic LOF variants in MYZAP and a phenotype of DCM (PMIDs: 34899865; 35840178; 38436102). Studies in zebrafish and mice demonstrate the link between MYZAP and cardiomyopathy (PMIDs: 20093627; 24698889). Overall, the evidence is sufficient to promote this gene to Green at the next GMS panel update.
Dilated and arrhythmogenic cardiomyopathy v2.21 MYZAP Arina Puzriakova Gene: myzap has been classified as Amber List (Moderate Evidence).
Dilated and arrhythmogenic cardiomyopathy v2.21 MYZAP Arina Puzriakova Classified gene: MYZAP as Amber List (moderate evidence)
Dilated and arrhythmogenic cardiomyopathy v2.21 MYZAP Arina Puzriakova Added comment: Comment on list classification: New gene added to the panel by Aleš Maver. MYZAP is not yet associated with any phenotype in OMIM or Gene2Phenoype. At least three unrelated families have been reported with biallelic LOF variants in MYZAP and a phenotype of DCM (PMIDs: 34899865; 35840178; 38436102). Studies in zebrafish and mice demonstrate the link between MYZAP and cardiomyopathy (PMIDs: 20093627; 24698889). Overall, the evidence is sufficient to promote this gene to Green at the next GMS panel update.
Dilated and arrhythmogenic cardiomyopathy v2.21 MYZAP Arina Puzriakova Gene: myzap has been classified as Amber List (Moderate Evidence).
Hypogonadotropic hypogonadism (GMS) v3.18 NDNF Arina Puzriakova Classified gene: NDNF as Green List (high evidence)
Hypogonadotropic hypogonadism (GMS) v3.18 NDNF Arina Puzriakova Added comment: Comment on list classification: Gene was re-reviewed in light of an Amber review by Zornitza Stark (Australian Genomics) on a Green gene. At least five unrelated cases have been reported, as well as mouse and zebrafish studies showing Ndnf deficiency leads to anomalies in GnRH neuron migration. Pedigree analysis does indicate variable expressivity and incomplete penetrance, although this is relatively common in dominant forms of HH. Furthermore, inclusion of NDNF on this panel has already been reviewed and approved by the NHS specialist group and therefore the Green rating is being maintained.
Hypogonadotropic hypogonadism (GMS) v3.18 NDNF Arina Puzriakova Gene: ndnf has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism (GMS) v3.17 NDNF Arina Puzriakova Phenotypes for gene: NDNF were changed from Congenital hypogonadotropic hypogonadism (CHH); Hypogonadotropic hypogonadism 25 with anosmia, 618841 to Hypogonadotropic hypogonadism 25 with anosmia, OMIM:618841
Hypogonadotropic hypogonadism (GMS) v3.16 NDNF Arina Puzriakova Publications for gene: NDNF were set to 31883645
Hypogonadotropic hypogonadism (GMS) v3.15 NDNF Arina Puzriakova commented on gene: NDNF: PMID: 36245975 (2022) - another male patient with idiopathic hypogonadotropin hypogonadism identified harbouring a paternally inherited NDNF variant (c.1439T>A, p.Ile480Asn)
Hereditary spastic paraplegia v1.311 RTN2 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: As there are sufficient number of cases with biallelic variants and lower limb spasticity, the MOI has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal'.
Hereditary spastic paraplegia v1.311 RTN2 Achchuthan Shanmugasundram Mode of inheritance for gene: RTN2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary spastic paraplegia v1.310 RTN2 Achchuthan Shanmugasundram Phenotypes for gene: RTN2 were changed from Spastic paraplegia 12, autosomal dominant to Spastic paraplegia 12, autosomal dominant, OMIM:604805; distal hereditary motor neuropathy, MONDO:0018894; Lower limb spasticity, HP:0002061
Hereditary spastic paraplegia v1.309 RTN2 Achchuthan Shanmugasundram Publications for gene: RTN2 were set to Montenegro et al. (2012)
Hereditary spastic paraplegia v1.308 RTN2 Achchuthan Shanmugasundram reviewed gene: RTN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 38527963; Phenotypes: distal hereditary motor neuropathy, MONDO:0018894, Lower limb spasticity, HP:0002061; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia v4.42 RTN2 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: As there are sufficient number of cases with biallelic variants and lower limb spasticity, the MOI should be updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' in the next GMS update.
Childhood onset hereditary spastic paraplegia v4.42 RTN2 Achchuthan Shanmugasundram Mode of inheritance for gene: RTN2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Childhood onset hereditary spastic paraplegia v4.41 RTN2 Achchuthan Shanmugasundram Phenotypes for gene: RTN2 were changed from Spastic paraplegia 12, autosomal dominant, 604805 to Spastic paraplegia 12, autosomal dominant, OMIM:604805; distal hereditary motor neuropathy, MONDO:0018894; Lower limb spasticity, HP:0002061
Childhood onset hereditary spastic paraplegia v4.40 RTN2 Achchuthan Shanmugasundram Publications for gene: RTN2 were set to 22232211; 24123792; 28362824
Childhood onset hereditary spastic paraplegia v4.39 RTN2 Achchuthan Shanmugasundram Tag Q2_24_MOI tag was added to gene: RTN2.
Tag Q2_24_NHS_review tag was added to gene: RTN2.
Hereditary neuropathy or pain disorder v3.89 RTN2 Achchuthan Shanmugasundram changed review comment from: PMID:38527963 reported the identification of seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven unrelated families with distal hereditary motor neuropathy.

All affected individuals exhibited weakness in the distal upper and lower limbs, lower limb spasticity, hyperreflexia, with an onset in the first decade of life. Nerve conduction studies revealed axonal motor neuropathy with neurogenic changes in the electromyography.

Characterisation of C. elegans RTN2 homolog loss-of-function variants demonstrated morphological and behavioural differences compared to the parental strain and treatment with an endoplasmic/sarcoplasmic reticulum Ca(2+) re-uptake inhibitor (2,5-di-tert-butylhydroquinone) rescued key phenotypic differences.

Biallelic variants in RTN2 gene have not yet been associated with any phenotypes in OMIM or Gene2Phenotype, while monoallelic variants have been associated with spastic paraplegia (MIM #604805) in OMIM.
Sources: Literature; to: PMID:38527963 reported the identification of seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven unrelated families with distal hereditary motor neuropathy.

All affected individuals exhibited weakness in the distal upper and lower limbs, lower limb spasticity, hyperreflexia, with an onset in the first decade of life. Nerve conduction studies revealed axonal motor neuropathy with neurogenic changes in the electromyography.

Characterisation of C. elegans RTN2 homolog loss-of-function variants demonstrated morphological and behavioural differences compared to the parental strain, and treatment with an endoplasmic/sarcoplasmic reticulum Ca(2+) re-uptake inhibitor (2,5-di-tert-butylhydroquinone) rescued key phenotypic differences.

Biallelic variants in RTN2 gene have not yet been associated with any phenotypes in OMIM or Gene2Phenotype, while monoallelic variants have been associated with spastic paraplegia (MIM #604805) in OMIM.
Sources: Literature
Childhood onset hereditary spastic paraplegia v4.39 RTN2 Achchuthan Shanmugasundram reviewed gene: RTN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 38527963; Phenotypes: distal hereditary motor neuropathy, MONDO:0018894, Lower limb spasticity, HP:0002061; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v3.89 RTN2 Achchuthan Shanmugasundram changed review comment from: PMID:38527963 reported the identification of seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven unrelated families with distal hereditary motor neuropathy.

All affected individuals (seven males and seven females, aged 9-50 years) exhibited weakness in the distal upper and lower limbs, lower limb spasticity, hyperreflexia, with an onset in the first decade of life. Nerve conduction studies revealed axonal motor neuropathy with neurogenic changes in the electromyography.

Characterisation of C. elegans RTN2 homolog loss-of-function variants demonstrated morphological and behavioural differences compared to the parental strain and treatment with an endoplasmic/sarcoplasmic reticulum Ca(2+) re-uptake inhibitor (2,5-di-tert-butylhydroquinone) rescued key phenotypic differences.

Biallelic variants in RTN2 gene have not yet been associated with any phenotypes in OMIM or Gene2Phenotype, while monoallelic variants have been associated with spastic paraplegia (MIM #604805) in OMIM.
Sources: Literature; to: PMID:38527963 reported the identification of seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven unrelated families with distal hereditary motor neuropathy.

All affected individuals exhibited weakness in the distal upper and lower limbs, lower limb spasticity, hyperreflexia, with an onset in the first decade of life. Nerve conduction studies revealed axonal motor neuropathy with neurogenic changes in the electromyography.

Characterisation of C. elegans RTN2 homolog loss-of-function variants demonstrated morphological and behavioural differences compared to the parental strain and treatment with an endoplasmic/sarcoplasmic reticulum Ca(2+) re-uptake inhibitor (2,5-di-tert-butylhydroquinone) rescued key phenotypic differences.

Biallelic variants in RTN2 gene have not yet been associated with any phenotypes in OMIM or Gene2Phenotype, while monoallelic variants have been associated with spastic paraplegia (MIM #604805) in OMIM.
Sources: Literature
Rare genetic inflammatory skin disorders v3.18 COL5A2 Arina Puzriakova Classified gene: COL5A2 as Red List (low evidence)
Rare genetic inflammatory skin disorders v3.18 COL5A2 Arina Puzriakova Added comment: Comment on list classification: Demoted from Amber to Red inline with review by Dmitrijs Rots.
Rare genetic inflammatory skin disorders v3.18 COL5A2 Arina Puzriakova Gene: col5a2 has been classified as Red List (Low Evidence).
Rare genetic inflammatory skin disorders v3.17 COL5A1 Arina Puzriakova Classified gene: COL5A1 as Red List (low evidence)
Rare genetic inflammatory skin disorders v3.17 COL5A1 Arina Puzriakova Added comment: Comment on list classification: Demoted from Amber to Red inline with review by Dmitrijs Rots.
Rare genetic inflammatory skin disorders v3.17 COL5A1 Arina Puzriakova Gene: col5a1 has been classified as Red List (Low Evidence).
Rare genetic inflammatory skin disorders v3.16 COL4A5 Arina Puzriakova Classified gene: COL4A5 as Red List (low evidence)
Rare genetic inflammatory skin disorders v3.16 COL4A5 Arina Puzriakova Added comment: Comment on list classification: Demoted from Amber to Red inline with review by Dmitrijs Rots.
Rare genetic inflammatory skin disorders v3.16 COL4A5 Arina Puzriakova Gene: col4a5 has been classified as Red List (Low Evidence).
Rare genetic inflammatory skin disorders v3.15 COL4A4 Arina Puzriakova Classified gene: COL4A4 as Red List (low evidence)
Rare genetic inflammatory skin disorders v3.15 COL4A4 Arina Puzriakova Added comment: Comment on list classification: Demoted from Amber to Red inline with review by Dmitrijs Rots.
Rare genetic inflammatory skin disorders v3.15 COL4A4 Arina Puzriakova Gene: col4a4 has been classified as Red List (Low Evidence).
Rare genetic inflammatory skin disorders v3.14 COL4A3 Arina Puzriakova Classified gene: COL4A3 as Red List (low evidence)
Rare genetic inflammatory skin disorders v3.14 COL4A3 Arina Puzriakova Added comment: Comment on list classification: Demoted from Amber to Red inline with review by Dmitrijs Rots.
Rare genetic inflammatory skin disorders v3.14 COL4A3 Arina Puzriakova Gene: col4a3 has been classified as Red List (Low Evidence).
Rare genetic inflammatory skin disorders v3.13 COL3A1 Arina Puzriakova Classified gene: COL3A1 as Red List (low evidence)
Rare genetic inflammatory skin disorders v3.13 COL3A1 Arina Puzriakova Added comment: Comment on list classification: Demoted from Amber to Red inline with review by Dmitrijs Rots.
Rare genetic inflammatory skin disorders v3.13 COL3A1 Arina Puzriakova Gene: col3a1 has been classified as Red List (Low Evidence).
Rare genetic inflammatory skin disorders v3.12 COL1A2 Arina Puzriakova Classified gene: COL1A2 as Red List (low evidence)
Rare genetic inflammatory skin disorders v3.12 COL1A2 Arina Puzriakova Added comment: Comment on list classification: Demoted from Amber to Red inline with review by Dmitrijs Rots.
Rare genetic inflammatory skin disorders v3.12 COL1A2 Arina Puzriakova Gene: col1a2 has been classified as Red List (Low Evidence).
Rare genetic inflammatory skin disorders v3.11 COL1A1 Arina Puzriakova Classified gene: COL1A1 as Red List (low evidence)
Rare genetic inflammatory skin disorders v3.11 COL1A1 Arina Puzriakova Added comment: Comment on list classification: Demoted from Amber to Red inline with review by Dmitrijs Rots.
Rare genetic inflammatory skin disorders v3.11 COL1A1 Arina Puzriakova Gene: col1a1 has been classified as Red List (Low Evidence).
Autoinflammatory disorders v1.17 IL17RA Arina Puzriakova Tag watchlist tag was added to gene: IL17RA.
Autoinflammatory disorders v1.17 IL17RA Arina Puzriakova Classified gene: IL17RA as Amber List (moderate evidence)
Autoinflammatory disorders v1.17 IL17RA Arina Puzriakova Added comment: Comment on list classification: New gene added to this panel by Lauma Freimane (Children's Clinical University Hospital). Biallelic variants have been found patients with immunodeficiency, presenting as chronic mucocutaneous candidiasis (PMID: 21350122).

Interleukin-17A (IL-17A) is a pro-inflammatory cytokine implicated in diverse autoimmune and inflammatory disorders such as psoriasis and Kawasaki disease so it is plausible that the interleukin-17A receptor (IL-17RA) could contribute to the same pathway.

Literature review did reveal multiple mouse models where IL-17RA was shown to promote the inflammatory response (PMID: 38060620; 30364284; 35844540; 38451335); however, there is no evidence of human cases where a variant in the IL17RA gene caused an autoinflammatory disorder. Therefore rating as Amber with a watchlist tag, awaiting further evidence.
Autoinflammatory disorders v1.17 IL17RA Arina Puzriakova Gene: il17ra has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.199 IL17RA Arina Puzriakova Added comment: Comment on phenotypes: Previous phenotypes: Candidiasis, familial, 5;Chronic mucocutaneous candidiasis (CMC);Immunodeficiency 51, 613953;Defects in Intrinsic and Innate Immunity;CMC, folliculitis;Defects in Intrinsic and Innate Immunity
Primary immunodeficiency or monogenic inflammatory bowel disease v4.199 IL17RA Arina Puzriakova Phenotypes for gene: IL17RA were changed from Candidiasis, familial, 5; Chronic mucocutaneous candidiasis (CMC); Immunodeficiency 51, 613953; Defects in Intrinsic and Innate Immunity; CMC, folliculitis; Defects in Intrinsic and Innate Immunity to Immunodeficiency 51, OMIM:613953
Autoinflammatory disorders v1.16 IL17RA Arina Puzriakova Phenotypes for gene: IL17RA were changed from Immunodeficiency-51 to Immunodeficiency 51, OMIM:613953
Likely inborn error of metabolism v4.137 ADA Arina Puzriakova Added comment: Comment on phenotypes: Previous phenotypes: Combined B and T cell defect;Adenosine deaminase deficiency (Disorders of purine metabolism);SCID;Infantile enterocolitis & monogenic inflammatory bowel disease
Likely inborn error of metabolism v4.137 ADA Arina Puzriakova Phenotypes for gene: ADA were changed from Severe combined immunodeficiency due to ADA deficiency, OMIM:102700; Adenosine deaminase deficiency, partial, OMIM:102700 to Severe combined immunodeficiency due to ADA deficiency, OMIM:102700; Adenosine deaminase deficiency, partial, OMIM:102700
Likely inborn error of metabolism v4.136 ADA Arina Puzriakova Added comment: Comment on phenotypes: Previous phenotypes: Combined B and T cell defect;Adenosine deaminase deficiency (Disorders of purine metabolism);SCID;Infantile enterocolitis & monogenic inflammatory bowel disease
Likely inborn error of metabolism v4.136 ADA Arina Puzriakova Phenotypes for gene: ADA were changed from Combined B and T cell defect; Adenosine deaminase deficiency (Disorders of purine metabolism); SCID; Infantile enterocolitis & monogenic inflammatory bowel disease to Severe combined immunodeficiency due to ADA deficiency, OMIM:102700; Adenosine deaminase deficiency, partial, OMIM:102700
Primary immunodeficiency or monogenic inflammatory bowel disease v4.198 ADA Arina Puzriakova Added comment: Comment on phenotypes: Previous phenotypes: Severe combined immunodeficiency due to ADA deficiency (some mosiacism noted);Severe combined immunodeficiency due to ADA deficiency, 102700;T-B- SCID;T-B+ SCID;Adenosine deaminase (ADA) deficiency;Atypical Severe Combined Immunodeficiency (Atypical SCID);Omenn syndrome;Severe combined immunodeficiency (SCID);Low NK, bone defects, may have pulmonary alveolar proteinosis, cognitive defects;Immunodeficiencies affecting cellular and humoral immunity
Primary immunodeficiency or monogenic inflammatory bowel disease v4.198 ADA Arina Puzriakova Phenotypes for gene: ADA were changed from Severe combined immunodeficiency due to ADA deficiency (some mosiacism noted); Severe combined immunodeficiency due to ADA deficiency, 102700; T-B- SCID; T-B+ SCID; Adenosine deaminase (ADA) deficiency; Atypical Severe Combined Immunodeficiency (Atypical SCID); Omenn syndrome; Severe combined immunodeficiency (SCID); Low NK, bone defects, may have pulmonary alveolar proteinosis, cognitive defects; Immunodeficiencies affecting cellular and humoral immunity to Severe combined immunodeficiency due to ADA deficiency, OMIM:102700; Adenosine deaminase deficiency, partial, OMIM:102700
Fetal anomalies v3.154 ADA Arina Puzriakova Phenotypes for gene: ADA were changed from Combined B and T cell defect; Adenosine deaminase deficiency (Disorders of purine metabolism); SCID; Infantile enterocolitis & monogenic inflammatory bowel disease to Severe combined immunodeficiency due to ADA deficiency, OMIM:102700; Adenosine deaminase deficiency, partial, OMIM:102700
Fetal anomalies v3.153 ADA Arina Puzriakova Phenotypes for gene: ADA were changed from ADENOSINE DEAMINASE DEFICIENCY to Combined B and T cell defect; Adenosine deaminase deficiency (Disorders of purine metabolism); SCID; Infantile enterocolitis & monogenic inflammatory bowel disease
Undiagnosed metabolic disorders v1.617 ADA Arina Puzriakova Added comment: Comment on phenotypes: Previous phenotypes: Adenosine deaminase deficiency (Disorders of purine metabolism);Combined B and T cell defect;Infantile enterocolitis & monogenic inflammatory bowel disease;SCID
Undiagnosed metabolic disorders v1.617 ADA Arina Puzriakova Phenotypes for gene: ADA were changed from Adenosine deaminase deficiency (Disorders of purine metabolism); Combined B and T cell defect; Infantile enterocolitis & monogenic inflammatory bowel disease; SCID to Severe combined immunodeficiency due to ADA deficiency, OMIM:102700; Adenosine deaminase deficiency, partial, OMIM:102700
Intellectual disability v5.524 ADA Arina Puzriakova Phenotypes for gene: ADA were changed from Severe combined immunodeficiency due to ADA deficiency, 102700; Adenosine deaminase deficiency, partial, 102700 to Severe combined immunodeficiency due to ADA deficiency, OMIM:102700; Adenosine deaminase deficiency, partial, OMIM:102700
Severe combined immunodeficiency with adenosine deaminase deficiency v1.3 ADA Arina Puzriakova Phenotypes for gene: ADA were changed from Severe combined immunodeficiency due to ADA deficiency, OMIM:102700; Adenosine deaminase deficiency, partial, OMIM:102700 to Severe combined immunodeficiency due to ADA deficiency, OMIM:102700
Severe combined immunodeficiency with adenosine deaminase deficiency v1.2 ADA Arina Puzriakova Phenotypes for gene: ADA were changed from to Severe combined immunodeficiency due to ADA deficiency, OMIM:102700; Adenosine deaminase deficiency, partial, OMIM:102700
Autoinflammatory disorders v1.15 ADA Arina Puzriakova Phenotypes for gene: ADA were changed from T(-), B(-), NK(-) severe combin immunodeficiency to Severe combined immunodeficiency due to ADA deficiency, OMIM:102700; Adenosine deaminase deficiency, partial, OMIM:102700
Bleeding and platelet disorders v3.9 GP6 Arina Puzriakova Phenotypes for gene: GP6 were changed from 614201 Bleeding disorder, platelet-type, 11 to Bleeding disorder, platelet-type, 11, OMIM:614201
Inherited bleeding disorders v1.177 GP6 Arina Puzriakova Phenotypes for gene: GP6 were changed from Bleeding diathesis due to glycoprotein VI deficiency to Bleeding disorder, platelet-type, 11, OMIM:614201
Autoinflammatory disorders v1.14 GP6 Arina Puzriakova Phenotypes for gene: GP6 were changed from Platlet-type bleeding disorder-11 to Bleeding disorder, platelet-type, 11, OMIM:614201
Autoinflammatory disorders v1.13 GP6 Arina Puzriakova Classified gene: GP6 as Red List (low evidence)
Autoinflammatory disorders v1.13 GP6 Arina Puzriakova Added comment: Comment on list classification: New gene added to this panel by Lauma Freimane (Children's Clinical University Hospital). Biallelic variants are associated with bleeding disorder caused by defective platelet activation and aggregation in response to collagen. Could not find evidence of an autoinflammatory component observed in patients and therefore rating as Red on this panel
Autoinflammatory disorders v1.13 GP6 Arina Puzriakova Gene: gp6 has been classified as Red List (Low Evidence).
Autoinflammatory disorders v1.12 ADA Arina Puzriakova Classified gene: ADA as Red List (low evidence)
Autoinflammatory disorders v1.12 ADA Arina Puzriakova Added comment: Comment on list classification: New gene added to this panel by Lauma Freimane (Children's Clinical University Hospital). Biallelic variants are associated with partial ADA deficiency or severe combined immunodeficiency (SCID) due to ADA deficiency with multiple unrelated cases reported.

Despite ADA null mice displaying severe pulmonary inflammation, could not find evidence of an autoinflammatory component observed in patients and therefore rating as Red on this panel
Autoinflammatory disorders v1.12 ADA Arina Puzriakova Gene: ada has been classified as Red List (Low Evidence).
Hereditary neuropathy or pain disorder v3.89 RTN2 Achchuthan Shanmugasundram Classified gene: RTN2 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v3.89 RTN2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the association of RTN2 biallelic variants with distal hereditary motor neuropathy. Hence, this gene should be promoted to green rating in the next GMS update.
Hereditary neuropathy or pain disorder v3.89 RTN2 Achchuthan Shanmugasundram Gene: rtn2 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v3.88 RTN2 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: RTN2.
Hereditary neuropathy or pain disorder v3.88 RTN2 Achchuthan Shanmugasundram gene: RTN2 was added
gene: RTN2 was added to Hereditary neuropathy or pain disorder. Sources: Literature
Mode of inheritance for gene: RTN2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RTN2 were set to 38527963
Phenotypes for gene: RTN2 were set to distal hereditary motor neuropathy, MONDO:0018894
Review for gene: RTN2 was set to GREEN
Added comment: PMID:38527963 reported the identification of seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven unrelated families with distal hereditary motor neuropathy.

All affected individuals (seven males and seven females, aged 9-50 years) exhibited weakness in the distal upper and lower limbs, lower limb spasticity, hyperreflexia, with an onset in the first decade of life. Nerve conduction studies revealed axonal motor neuropathy with neurogenic changes in the electromyography.

Characterisation of C. elegans RTN2 homolog loss-of-function variants demonstrated morphological and behavioural differences compared to the parental strain and treatment with an endoplasmic/sarcoplasmic reticulum Ca(2+) re-uptake inhibitor (2,5-di-tert-butylhydroquinone) rescued key phenotypic differences.

Biallelic variants in RTN2 gene have not yet been associated with any phenotypes in OMIM or Gene2Phenotype, while monoallelic variants have been associated with spastic paraplegia (MIM #604805) in OMIM.
Sources: Literature
Fetal anomalies v3.152 NRXN2 Sarah Leigh Classified gene: NRXN2 as Red List (low evidence)
Fetal anomalies v3.152 NRXN2 Sarah Leigh Added comment: Comment on list classification: There insufficient evidence between NRXN2 variants and autism for this gene to be rated amber.
Fetal anomalies v3.152 NRXN2 Sarah Leigh Gene: nrxn2 has been classified as Red List (Low Evidence).
Iron metabolism disorders - NOT common HFE mutations v2.6 CYBRD1 Sarah Leigh Publications for gene: CYBRD1 were set to 15338274; 27884173
Iron metabolism disorders - NOT common HFE mutations v2.5 CYBRD1 Sarah Leigh edited their review of gene: CYBRD1: Added comment: It would appear that there are no CYBRD1 rare SNVs associated with iron metabolism.  However, PMID: 37632052 concludes that the coexistence of minor alleles of HDAC3 rs976552 and CYBRD1 rs884409 is linked with higher prevalence of hepatocellular carcinoma.

Furthermore, HFE p.C282Y variant together with the CYBRD1 polymorphism rs884409 reduces CYBRD1 promoter activity by 30% (PMID: 19673882).; Changed rating: AMBER
Bilateral congenital or childhood onset cataracts v4.12 LIM2 Arina Puzriakova changed review comment from: Comment on mode of inheritance: The MOI should be updated from 'biallelic' to 'both mono- and biallelic' at the next GMS panel update. At least 9 unrelated multigenerational families have been identified with congenital cataracts due to a recurrent heterozygous LIM2 p.R130C variant (PMIDs: 32202185; 33078099; 33708862; 33923544; 35736209). These families come from different ancestries (British, Chinese, Spanish, Japanese) and haplotype analysis in families from shared ancestries has suggested the variant likely arose due to independent founder events in each family. The evidence therefore supports this MOI being included in future analyses.; to: Comment on mode of inheritance: The MOI should be updated from 'biallelic' to 'both mono- and biallelic' at the next GMS panel update. At least 9 unrelated multigenerational families have been identified with cataracts due to a recurrent heterozygous LIM2 p.R130C variant (PMIDs: 32202185; 33078099; 33708862; 33923544; 35736209). These families come from different ancestries (British, Chinese, Spanish, Japanese) and haplotype analysis in families from shared ancestries has suggested the variant likely arose due to independent founder events in each family. The evidence therefore supports this MOI being included in future analyses.
Bilateral congenital or childhood onset cataracts v4.12 LIM2 Arina Puzriakova changed review comment from: Comment on mode of inheritance: The MOI should be updated from 'biallelic' to 'both mono- and biallelic' at the next GMS panel update. At least 9 unrelated multigenerational families have been identified with congenital cataracts due to a recurrent LIM2 p.R130C variant (PMIDs: 32202185; 33078099; 33708862; 33923544; 35736209). These families come from different ancestries (British, Chinese, Spanish, Japanese) and haplotype analysis in families from shared ancestries has suggested the variant likely arose due to independent founder events in each family. The evidence therefore supports this MOI being included in future analyses.; to: Comment on mode of inheritance: The MOI should be updated from 'biallelic' to 'both mono- and biallelic' at the next GMS panel update. At least 9 unrelated multigenerational families have been identified with congenital cataracts due to a recurrent heterozygous LIM2 p.R130C variant (PMIDs: 32202185; 33078099; 33708862; 33923544; 35736209). These families come from different ancestries (British, Chinese, Spanish, Japanese) and haplotype analysis in families from shared ancestries has suggested the variant likely arose due to independent founder events in each family. The evidence therefore supports this MOI being included in future analyses.
Bilateral congenital or childhood onset cataracts v4.12 LIM2 Arina Puzriakova Tag recurrent-variant tag was added to gene: LIM2.
Tag Q2_24_MOI tag was added to gene: LIM2.
Bilateral congenital or childhood onset cataracts v4.12 LIM2 Arina Puzriakova changed review comment from: Comment on mode of inheritance: The MOI should be updated from 'biallelic' to 'both mono- and biallelic' at the next GMS panel update. At least 9 unrelated multigenerational families have been identified with congenital cataracts due to a recurrent LIM2 p.R130C variant. These families come from different ancestries (British, Chinese, Spanish, Japanese) and haplotype analysis in families from shared ancestries has suggested the variant likely arose due to independent founder events in each family. The evidence therefore supports this MOI being included in future analyses.; to: Comment on mode of inheritance: The MOI should be updated from 'biallelic' to 'both mono- and biallelic' at the next GMS panel update. At least 9 unrelated multigenerational families have been identified with congenital cataracts due to a recurrent LIM2 p.R130C variant (PMIDs: 32202185; 33078099; 33708862; 33923544; 35736209). These families come from different ancestries (British, Chinese, Spanish, Japanese) and haplotype analysis in families from shared ancestries has suggested the variant likely arose due to independent founder events in each family. The evidence therefore supports this MOI being included in future analyses.
Bilateral congenital or childhood onset cataracts v4.12 LIM2 Arina Puzriakova Added comment: Comment on mode of inheritance: The MOI should be updated from 'biallelic' to 'both mono- and biallelic' at the next GMS panel update. At least 9 unrelated multigenerational families have been identified with congenital cataracts due to a recurrent LIM2 p.R130C variant. These families come from different ancestries (British, Chinese, Spanish, Japanese) and haplotype analysis in families from shared ancestries has suggested the variant likely arose due to independent founder events in each family. The evidence therefore supports this MOI being included in future analyses.
Bilateral congenital or childhood onset cataracts v4.12 LIM2 Arina Puzriakova Mode of inheritance for gene: LIM2 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v3.87 CADM3 Ian Berry reviewed gene: CADM3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38074074, 33889941; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Bilateral congenital or childhood onset cataracts v4.11 LIM2 Arina Puzriakova Publications for gene: LIM2 were set to Ponnam et al (2008) Mol Vis 14:1204-1208; Pras et al (2002) Am J Hum genet 70:1363-7
Bilateral congenital or childhood onset cataracts v4.10 LIM2 Arina Puzriakova Phenotypes for gene: LIM2 were changed from Cortical Pulverulent Cataract; Cataract 19, 615277 to Cataract 19, multiple types, OMIM:615277
Structural eye disease v3.77 LIM2 Arina Puzriakova Phenotypes for gene: LIM2 were changed from Cataract 19, 615277 to Cataract 19, multiple types, OMIM:615277
Intellectual disability v5.523 FRYL Arina Puzriakova Classified gene: FRYL as Amber List (moderate evidence)
Intellectual disability v5.523 FRYL Arina Puzriakova Added comment: Comment on list classification: Rating Amber as overall the evidence is borderline. Only one recent study (PMID:38479391) has reported an disease association for FRYL, with variable phenotypes and results from functional studies, as well as variants in other genes in several cases. Additional studies are required to conclusively corroborate causality (added watchlist tag).
Intellectual disability v5.523 FRYL Arina Puzriakova Gene: fryl has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.522 FRYL Arina Puzriakova gene: FRYL was added
gene: FRYL was added to Intellectual disability - microarray and sequencing. Sources: Literature
watchlist tags were added to gene: FRYL.
Mode of inheritance for gene: FRYL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FRYL were set to 38479391
Phenotypes for gene: FRYL were set to Neurodevelopmental disorder, MONDO:0700092
Review for gene: FRYL was set to AMBER
Added comment: New association linking this gene to disease which is not yet listed in OMIM or Gene2Phenotype. There are no sequence variants in Decipher and ClinVar shows only a single pathogenic frameshift variant (c.1224del, p.Lys409fs) for FRYL-associated neurodevelopmental disorder, amongst multiple SNVs which are mostly missense VUS or B/LB.

Pan et al., 2024 (PMID: 38479391) reported 14 individuals with heterozygous variant in FRYL who presented with DD/ID, dysmorphic features, and other congenital anomalies in multiple systems. Except for DD/ID which was the only universal feature, observed phenotypes were variable and nonspecific.

Variants were confirmed de novo in all except one individual (duo testing excluded paternal inheritance although it was present at low frequency in gnomAD). Variant types include missense (5), fs/stop-gain (8) and canonical splice (1). Modelling 4/5 patient missense variants using flies showed that only one serves as a severe LoF variant, two others behave as partial LoF variants, and one variant had no functional impact (only variant not confirmed as de novo indicating this is a VUS). Four individuals also had P/LP variants in other genes (SF3B4, DHCR7, SLC6A19, SDHA) which could at least partially explain their phenotypes, and a further four harboured additional VUSs.
Sources: Literature
RASopathies v1.81 RRAS Sarah Leigh Classified gene: RRAS as Green List (high evidence)
RASopathies v1.81 RRAS Sarah Leigh Gene: rras has been classified as Green List (High Evidence).
RASopathies v1.80 RRAS Sarah Leigh Tag Q2_24_promote_green was removed from gene: RRAS.
RASopathies v1.80 RRAS Sarah Leigh Tag Q2_24_promote_green tag was added to gene: RRAS.
Fetal anomalies v3.151 RRAS Sarah Leigh Tag Q2_24_promote_green tag was added to gene: RRAS.
Cytopenia - NOT Fanconi anaemia v3.31 RRAS Sarah Leigh Tag Q2_24_promote_green tag was added to gene: RRAS.
RASopathies v1.80 RRAS Sarah Leigh Publications for gene: RRAS were set to 24705357
RASopathies v1.79 RRAS Sarah Leigh edited their review of gene: RRAS: Added comment: RRAS variants have not associated with a phenotype in OMIM or MONDO, but Gen2Phen lists a strong association between RRAS variants and RRAS-related atypical Noonan syndrome. Three germline RRAS variants have been reported (PMID: 24705357; 32815881; 34935735), associated with a RASopathy, which includes myelodysplastic syndrome and contributes to leukaemogenesis.; Changed rating: GREEN; Changed publications to: 24705357, 32815881, 34935735
Fetal anomalies v3.151 RRAS Sarah Leigh edited their review of gene: RRAS: Added comment: RRAS variants have not associated with a phenotype in OMIM or MONDO, but Gen2Phen lists a strong association between RRAS variants and RRAS-related atypical Noonan syndrome. Three germline RRAS variants have been reported (PMID: 24705357; 32815881; 34935735), associated with a RASopathy, which includes myelodysplastic syndrome and contributes to leukaemogenesis.; Changed rating: GREEN; Changed publications to: 24705357, 32815881, 34935735
Cytopenia - NOT Fanconi anaemia v3.31 RRAS Sarah Leigh Publications for gene: RRAS were set to 34935735
Cytopenia - NOT Fanconi anaemia v3.30 RRAS Sarah Leigh commented on gene: RRAS: RRAS variants have not associated with a phenotype in OMIM or MONDO, but Gen2Phen lists a strong association between RRAS variants and RRAS-related atypical Noonan syndrome. Three germline RRAS variants have been reported (PMID: 24705357; 32815881; 34935735), associated with a RASopathy, which includes myelodysplastic syndrome and contributes to leukaemogenesis.
RASopathies v1.79 RRAS Sarah Leigh Added comment: Comment on phenotypes: Phenotype from Gen2Phen
RASopathies v1.79 RRAS Sarah Leigh Phenotypes for gene: RRAS were changed from Noonan syndrome to RRAS-related atypical Noonan syndrome
Fetal anomalies v3.151 RRAS Sarah Leigh Added comment: Comment on phenotypes: Phenotype from Gen2Phen
Fetal anomalies v3.151 RRAS Sarah Leigh Phenotypes for gene: RRAS were changed from ATYPICAL NOONAN SYNDROME to RRAS-related atypical Noonan syndrome
Fetal anomalies v3.150 RRAS Sarah Leigh Publications for gene: RRAS were set to
Cytopenia - NOT Fanconi anaemia v3.30 RRAS Sarah Leigh edited their review of gene: RRAS: Added comment: RRAS variants have not associated with a phenotype in OMIM or MONDO, but Gen2Phen lists a strong association between RRAS variants and RRAS-related atypical Noonan syndrome. Three germline RRAS variants have been reported (PMID: 24705357; 32815881; 34935735), associated with a RASopathy, which includes myelodysplastic syndrome and contributes to leukaemogenesis.; Changed rating: GREEN; Changed publications to: 24705357, 32815881, 34935735; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Cytopenia - NOT Fanconi anaemia v3.30 RRAS Sarah Leigh Added comment: Comment on phenotypes: RRAS-related atypical Noonan syndrome phenotype from Gen2Phen
Cytopenia - NOT Fanconi anaemia v3.30 RRAS Sarah Leigh Phenotypes for gene: RRAS were changed from Pediatric Myelodysplastic Syndrome to RRAS-related atypical Noonan syndrome
Cytopenia - NOT Fanconi anaemia v3.29 RRAS Sarah Leigh Publications for gene: RRAS were set to PMID: 34935735
Cytopenia - NOT Fanconi anaemia v3.28 RRAS Sarah Leigh Classified gene: RRAS as Amber List (moderate evidence)
Cytopenia - NOT Fanconi anaemia v3.28 RRAS Sarah Leigh Gene: rras has been classified as Amber List (Moderate Evidence).
Hereditary ataxia with onset in adulthood v4.31 NAA60 Sarah Leigh commented on gene: NAA60: NAA60 should be green on the Hereditary ataxia with onset in adulthood as four of the families described in table 1 (PMID: 38480682), also displayed either cerebellar syndrome (which often includes ataxia) or cerebellar ataxia (personal communication from Helen Brittain (Genomics England Clinical Fellow).
Adult onset neurodegenerative disorder v4.47 NAA60 Sarah Leigh changed review comment from: To date, NAA60 variants are not associated with a phenotype in OMIM, Gen2Phen or MONDO. PMID: 38480682 reports six NAA60 variants in six unrelated cases with an autosomal recessive primary familial brain calcification (PFBC). Table 2 in PMID: 38480682 outlines the extent of the calcification seen in the patient's CT scans. Functional studies show that the phosphate importer SLC20A2 is a substrate of NAA60 in vitro, and loss of function by the NAA60 variants results in a reduced level of surface SLC20A2, thereby, reducing the extracellular phosphate uptake. The authors conclude, that this study provides a possible biochemical explanation of the involvement of NAA60 variants in PFBC development (PMID: 38480682).
Sources: Literature; to: To date, NAA60 variants are not associated with a phenotype in OMIM, Gen2Phen or MONDO. PMID: 38480682 reports six NAA60 variants in six unrelated cases with an autosomal recessive primary familial brain calcification (PFBC); signs of Parkinsonian presentation was evident in three families reported. Table 2 in PMID: 38480682 outlines the extent of the calcification seen in the patient's CT scans. Functional studies show that the phosphate importer SLC20A2 is a substrate of NAA60 in vitro, and loss of function by the NAA60 variants results in a reduced level of surface SLC20A2, thereby, reducing the extracellular phosphate uptake. The authors conclude, that this study provides a possible biochemical explanation of the involvement of NAA60 variants in PFBC development (PMID: 38480682).
Sources: Literature
Hereditary ataxia with onset in adulthood v4.31 NAA60 Sarah Leigh Tag Q2_24_MOI tag was added to gene: NAA60.
Adult onset neurodegenerative disorder v4.47 NAA60 Sarah Leigh Tag Q2_24_MOI tag was added to gene: NAA60.
White matter disorders and cerebral calcification - narrow panel v3.35 NAA60 Sarah Leigh Tag Q2_24_MOI tag was added to gene: NAA60.
Hereditary ataxia with onset in adulthood v4.31 NAA60 Sarah Leigh Entity copied from White matter disorders and cerebral calcification - narrow panel v3.35
Hereditary ataxia with onset in adulthood v4.31 NAA60 Sarah Leigh gene: NAA60 was added
gene: NAA60 was added to Hereditary ataxia with onset in adulthood. Sources: Literature,Expert Review Amber
Q2_24_promote_green, Q2_24_NHS_review tags were added to gene: NAA60.
Mode of inheritance for gene: NAA60 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAA60 were set to 38480682
Phenotypes for gene: NAA60 were set to NAA60 associated autosomal recessive primary familial brain calcifications
Adult onset neurodegenerative disorder v4.47 NAA60 Sarah Leigh Entity copied from White matter disorders and cerebral calcification - narrow panel v3.35
Adult onset neurodegenerative disorder v4.47 NAA60 Sarah Leigh gene: NAA60 was added
gene: NAA60 was added to Adult onset neurodegenerative disorder. Sources: Literature,Expert Review Amber
Q2_24_promote_green, Q2_24_NHS_review tags were added to gene: NAA60.
Mode of inheritance for gene: NAA60 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAA60 were set to 38480682
Phenotypes for gene: NAA60 were set to NAA60 associated autosomal recessive primary familial brain calcifications
White matter disorders and cerebral calcification - narrow panel v3.35 NAA60 Sarah Leigh changed review comment from: To date, NAA60 variants are not associated with a phenotype in OMIM, Gen2Phen or MONDO. PMID: 38480682 reports six NAA60 variants in six unrelated cases with an autosomal recessive primary familial brain calcification (PFBC). Table 2 in PMID: 38480682 outlines the extent of the calcification seen in the patient's CT scans. Functional studies show that the phosphate importer SLC20A2 is a substrate of NAA60 in vitro, and loss of function by the NAA60 variants results in a reduced level of surface SLC20A2, thereby, reducing the extracellular phosphate uptake. The authors conclude, that this study provides a possible biochemical explanation of the involvement of NAA60 variants in PFBC development (PMID: 38480682).
Sources: Literature; to: To date, NAA60 variants are not associated with a phenotype in OMIM, Gen2Phen or MONDO. PMID: 38480682 reports six NAA60 variants in six unrelated cases with an autosomal recessive primary familial brain calcification (PFBC). Table 2 in PMID: 38480682 outlines the extent of the calcification seen in the patient's CT scans. Functional studies show that the phosphate importer SLC20A2 is a substrate of NAA60 in vitro, and loss of function by the NAA60 variants results in a reduced level of surface SLC20A2, thereby, reducing the extracellular phosphate uptake. The authors conclude, that this study provides a possible biochemical explanation of the involvement of NAA60 variants in PFBC development (PMID: 38480682).
Sources: Literature
White matter disorders and cerebral calcification - narrow panel v3.35 NAA60 Sarah Leigh Mode of inheritance for gene: NAA60 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v4.30 BTD Achchuthan Shanmugasundram Phenotypes for gene: BTD were changed from Biotinidase deficiency, OMIM:253260 to Biotinidase deficiency, OMIM:253260; optic atrophy, MONDO:0003608
Optic neuropathy v4.29 BTD Achchuthan Shanmugasundram edited their review of gene: BTD: Changed phenotypes to: Biotinidase deficiency, OMIM:253260, optic atrophy, MONDO:0003608
Optic neuropathy v4.29 BTD Achchuthan Shanmugasundram Classified gene: BTD as Amber List (moderate evidence)
Optic neuropathy v4.29 BTD Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Optic neuropathy v4.29 BTD Achchuthan Shanmugasundram Gene: btd has been classified as Amber List (Moderate Evidence).