Activity

Date Panel Item Activity
3000 actions
Genetic epilepsy syndromes v0.1052 GABRB2 Louise Daugherty Added comment: Comment on phenotypes: Added phenotypes suggested from expert review that indicate relevance to inclusion on the Genetic Epilepsy Syndromes panel
Genetic epilepsy syndromes v0.1052 GABRB2 Louise Daugherty Phenotypes for gene: GABRB2 were changed from to Epileptic encephalopathy, infantile or early childhood, 2, 617829
Thoracic aortic aneurysm or dissection v1.77 ABL1 Chris Buxton gene: ABL1 was added
gene: ABL1 was added to Thoracic aortic aneurysm or dissection. Sources: Literature
Mode of inheritance for gene: ABL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ABL1 were set to 28288113
Phenotypes for gene: ABL1 were set to Congenital finger flexion contractures (HP:0005879); Congenital septal defect (HP:0004760); Generalized joint laxity (HP:0002761); Ascending aortic dilation (HP:0004970); Scoliosis (HP:0002650); Failure to thrive in infancy (HP:0001531); Hypospadias (HP:0000047); Pectus excavatum (HP:0000767)
Penetrance for gene: ABL1 were set to unknown
Mode of pathogenicity for gene: ABL1 was set to Other
Review for gene: ABL1 was set to RED
Added comment: Gain of function variants in this gene are described by Wang (2017, PMID 28288113) as a ddx for TGFB overexpression pathway disorders, eg Loeys Dietz, Shprintzen Goldberg, Marfan syndrome.

Wang X et al., Germline mutations in ABL1 cause an autosomal dominant syndrome characterized by congenital heart defects and skeletal malformations. Nat Genet. 2017 Apr;49(4):613-617.
Sources: Literature
Genetic epilepsy syndromes v0.1051 GALC Louise Daugherty Marked gene: GALC as ready
Genetic epilepsy syndromes v0.1051 GALC Louise Daugherty Gene: galc has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.1051 GALC Louise Daugherty Classified gene: GALC as Green List (high evidence)
Genetic epilepsy syndromes v0.1051 GALC Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green. Appropriate phenotype, sufficient cases, and external review comment all support gene-disease association
Genetic epilepsy syndromes v0.1051 GALC Louise Daugherty Gene: galc has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.1050 PTS Sarah Leigh Classified gene: PTS as Red List (low evidence)
Genetic epilepsy syndromes v0.1050 PTS Sarah Leigh Added comment: Comment on list classification: Although the phenotype in OMIM and Gen2Phen gene. However, unable to find reports of seizures in variant carriers.
Genetic epilepsy syndromes v0.1050 PTS Sarah Leigh Gene: pts has been classified as Red List (Low Evidence).
Genetic epilepsy syndromes v0.1049 GALC Louise Daugherty Added comment: Comment on publications: Added publications to support upgrading of the gene to Green
Genetic epilepsy syndromes v0.1049 GALC Louise Daugherty Publications for gene: GALC were set to
Genetic epilepsy syndromes v0.1048 GALC Louise Daugherty Added comment: Comment on mode of inheritance: changed MOI from external clinical review and publications
Genetic epilepsy syndromes v0.1048 GALC Louise Daugherty Mode of inheritance for gene: GALC was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.1047 GALC Louise Daugherty Added comment: Comment on phenotypes: Added phenotypes suggested from expert review that indicate relevance to inclusion on the Genetic Epilepsy Syndromes panel
Genetic epilepsy syndromes v0.1047 GALC Louise Daugherty Phenotypes for gene: GALC were changed from to Krabbe disease, 245200; seizures; CALC deficiency; Galactosylceramide beta-galactosidase deficiency
Genetic epilepsy syndromes v0.1046 GAMT Louise Daugherty Marked gene: GAMT as ready
Genetic epilepsy syndromes v0.1046 GAMT Louise Daugherty Gene: gamt has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.1046 PIK3CA Eleanor Williams Added comment: Comment on mode of inheritance: Note somatic mosiacism
Genetic epilepsy syndromes v0.1046 PIK3CA Eleanor Williams Mode of inheritance for gene: PIK3CA was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic epilepsy syndromes v0.1045 PIK3CA Eleanor Williams Tag mosaicism tag was added to gene: PIK3CA.
Tag somatic tag was added to gene: PIK3CA.
Genetic epilepsy syndromes v0.1045 PIK3CA Eleanor Williams commented on gene: PIK3CA
Genetic epilepsy syndromes v0.1045 KCNQ5 Ivone Leong Classified gene: KCNQ5 as Green List (high evidence)
Genetic epilepsy syndromes v0.1045 KCNQ5 Ivone Leong Added comment: Comment on list classification: Promoted from amber to green. Have checked with Eleanor Williams (Genomic England) that two probands with different variants who have the same ethnic background is accepted as two separate pieces of evidence.
Genetic epilepsy syndromes v0.1045 KCNQ5 Ivone Leong Gene: kcnq5 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.1044 GAMT Louise Daugherty Added comment: Comment on phenotypes: added synonyms
Genetic epilepsy syndromes v0.1044 GAMT Louise Daugherty Phenotypes for gene: GAMT were changed from Cerebral creatine deficiency syndrome 2, 612736; Seizures; Deficiency of guanidinoacetate methyltransferase to Cerebral creatine deficiency syndrome 2, 612736; Seizures; Deficiency of guanidinoacetate methyltransferase; GAMT deficiency
Genetic epilepsy syndromes v0.1043 GAMT Louise Daugherty Publications for gene: GAMT were set to 15651030; 17101918; 15108290; 19027335
Genetic epilepsy syndromes v0.1042 GAMT Louise Daugherty Classified gene: GAMT as Green List (high evidence)
Genetic epilepsy syndromes v0.1042 GAMT Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green. Appropriate phenotype, sufficient cases, and external review comment all support gene-disease association
Genetic epilepsy syndromes v0.1042 GAMT Louise Daugherty Gene: gamt has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.1041 GAMT Louise Daugherty Added comment: Comment on publications: Added publications s to support upgrading of the gene to Green
Genetic epilepsy syndromes v0.1041 GAMT Louise Daugherty Publications for gene: GAMT were set to
Genetic epilepsy syndromes v0.1040 MAP2K1 Ivone Leong Publications for gene: MAP2K1 were set to
Genetic epilepsy syndromes v0.1039 GAMT Louise Daugherty Phenotypes for gene: GAMT were changed from Cerebral creatine deficiency syndrome 2, 612736; Seizures to Cerebral creatine deficiency syndrome 2, 612736; Seizures; Deficiency of guanidinoacetate methyltransferase
Genetic epilepsy syndromes v0.1038 GAMT Louise Daugherty Added comment: Comment on mode of inheritance: Added MOI from external clinical review and publications
Genetic epilepsy syndromes v0.1038 GAMT Louise Daugherty Mode of inheritance for gene: GAMT was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.1037 GAMT Louise Daugherty Added comment: Comment on phenotypes: Not added the expert review phenotype Krabbe disease as it related to the previously reviewed gene GALC. Cerebral creatine deficiency syndrome 2, 612736 is the disorder associated to variants of this gene, and is relevant for inclusion on the Genetic Epilepsy Syndromes panel
Genetic epilepsy syndromes v0.1037 GAMT Louise Daugherty Phenotypes for gene: GAMT were changed from to Cerebral creatine deficiency syndrome 2, 612736; Seizures
Genetic epilepsy syndromes v0.1036 MAP2K1 Ivone Leong Mode of inheritance for gene: MAP2K1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hearing loss v1.55 TBC1D24 Louise Daugherty Publications for gene: TBC1D24 were set to 10574461; 10741954; 20727515; 20797691; 21087195; 22211675; 23343562; 23526554; 24291220; 24387994; 24729539; 24729547
Hearing loss v1.54 TBC1D24 Louise Daugherty Classified gene: TBC1D24 as Green List (high evidence)
Hearing loss v1.54 TBC1D24 Louise Daugherty Added comment: Comment on list classification: Changed from Red to Green. Appropriate phenotype, sufficient cases, and external review comment all support gene-disease association
Hearing loss v1.54 TBC1D24 Louise Daugherty Gene: tbc1d24 has been classified as Green List (High Evidence).
Hearing loss v1.53 TBC1D24 Louise Daugherty Mode of inheritance for gene: TBC1D24 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hearing loss v1.52 TBC1D24 Louise Daugherty Added comment: Comment on publications: Added publications suggested from external expert review to support upgrading of the gene to Green
Hearing loss v1.52 TBC1D24 Louise Daugherty Publications for gene: TBC1D24 were set to
Hearing loss v1.51 TBC1D24 Louise Daugherty Phenotypes for gene: TBC1D24 were changed from Deafness , autosomal recessive 86, 614617; Deafness, autosomal dominant 65, 616044; DOORS syndrome, 220500; deafness, onychodystrophy, osteodystrophy, and mental retardation to Deafness, autosomal recessive 86, 614617; Deafness, autosomal dominant 65, 616044; DOORS syndrome, 220500; deafness, onychodystrophy, osteodystrophy, and mental retardation
Hearing loss v1.50 TBC1D24 Louise Daugherty Added comment: Comment on phenotypes: Added phenotypes that indicate relevance to inclusion on the Hearing loss panel from OMIM. removed: Myoclonic epilepsy, infantile, familial, 605021;Myoclonicepilepsy,infantile,familial,605021Epilepticencephalopathy,earlyinfantile,16,615338
Hearing loss v1.50 TBC1D24 Louise Daugherty Phenotypes for gene: TBC1D24 were changed from Myoclonic epilepsy, infantile, familial, 605021; Myoclonicepilepsy,infantile,familial,605021Epilepticencephalopathy,earlyinfantile,16,615338 to Deafness , autosomal recessive 86, 614617; Deafness, autosomal dominant 65, 616044; DOORS syndrome, 220500; deafness, onychodystrophy, osteodystrophy, and mental retardation
Genetic epilepsy syndromes v0.1035 MAP2K1 Ivone Leong Phenotypes for gene: MAP2K1 were changed from to Cardiofaciocutaneous syndrome 3, 615279
Genetic epilepsy syndromes v0.1034 PIGW Eleanor Williams Marked gene: PIGW as ready
Genetic epilepsy syndromes v0.1034 PIGW Eleanor Williams Added comment: Comment when marking as ready: Sufficient cases to make green
Genetic epilepsy syndromes v0.1034 PIGW Eleanor Williams Gene: pigw has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.1034 PIGW Eleanor Williams Phenotypes for gene: PIGW were changed from to Glycosylphosphatidylinositol biosynthesis defect 11, 616025; HYPERPHOSPHATASIA WITH MENTAL RETARDATION SYNDROME 5
Genetic epilepsy syndromes v0.1033 PIGW Eleanor Williams Publications for gene: PIGW were set to 24367057; 27626616; 30078644
Genetic epilepsy syndromes v0.1032 PIGW Eleanor Williams Publications for gene: PIGW were set to
Genetic epilepsy syndromes v0.1031 LIAS Ivone Leong Marked gene: LIAS as ready
Genetic epilepsy syndromes v0.1031 LIAS Ivone Leong Gene: lias has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.1031 LIAS Ivone Leong Classified gene: LIAS as Green List (high evidence)
Genetic epilepsy syndromes v0.1031 LIAS Ivone Leong Added comment: Comment on list classification: Promoted from amber to green. Phenotype confirmed by both OMIM and Gene2Phenotype.

There are only 4 reported cases of this disease in 3 papers (PMID: 24334290, 22152680, 26108146). Of the three cases, all patients (2 of Turkish descent and 1 of Somali descent) have different variants in the LIAS gene and they all have seizures (PMID: 24334290, 22152680).
Genetic epilepsy syndromes v0.1031 LIAS Ivone Leong Gene: lias has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.1030 PIGW Eleanor Williams Mode of inheritance for gene: PIGW was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.1029 PIGW Eleanor Williams Classified gene: PIGW as Green List (high evidence)
Genetic epilepsy syndromes v0.1029 PIGW Eleanor Williams Added comment: Comment on list classification: 3 cases/families reported, all with seizures
Genetic epilepsy syndromes v0.1029 PIGW Eleanor Williams Gene: pigw has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.1028 PIGW Eleanor Williams commented on gene: PIGW
Genetic epilepsy syndromes v0.1028 PIGO Eleanor Williams Marked gene: PIGO as ready
Genetic epilepsy syndromes v0.1028 PIGO Eleanor Williams Added comment: Comment when marking as ready: Sufficient cases with compound heterozygous mutations in PIGO and 3 cases with seizures.
Genetic epilepsy syndromes v0.1028 PIGO Eleanor Williams Gene: pigo has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.1028 PIGO Eleanor Williams Publications for gene: PIGO were set to 22683086; 24049131; 24417746; 28900819
Retinal disorders v1.88 SCAPER Louise Daugherty Added comment: Comment on phenotypes: added phenotype and MIM from OMIM : Tatour et al. (2017) PMID: 28794130 describes 4 patients from 3 unrelated families with intellectual disability disorder and retinitis pigmentosa and identified homozygosity or compound heterozygosity for mutations in the SCAPER gene. Noting that the retinal phenotype associated with null SCAPER mutations is not congenital but presents around the second decade of life, the authors suggested that in the retina, SCAPER does not play a developmental role, but rather is important for photoreceptor function and/or maintenance.
Retinal disorders v1.88 SCAPER Louise Daugherty Phenotypes for gene: SCAPER were changed from More than one phenotype including syndromic cases for syndromic forms of Inherited retinal disease or albinism to More than one phenotype including syndromic cases for syndromic forms of Inherited retinal disease or albinism; Intellectual developmental disorder and retinitis pigmentosa, 618195
Intellectual disability v2.553 SCAPER Louise Daugherty Added comment: Comment on publications: Added publications to support upgrading of the gene to Green
Intellectual disability v2.553 SCAPER Louise Daugherty Publications for gene: SCAPER were set to 21937992
Intellectual disability v2.552 SCAPER Louise Daugherty edited their review of gene: SCAPER: Changed rating: AMBER
Intellectual disability v2.552 SCAPER Louise Daugherty Added comment: Comment on phenotypes: added phenotype and MIM from OMIM : Tatour et al. (2017) PMID: 28794130 describes 4 patients from 3 unrelated families with intellectual disability disorder and retinitis pigmentosa and identified homozygosity or compound heterozygosity for mutations in the SCAPER gene. Noting that the retinal phenotype associated with null SCAPER mutations is not congenital but presents around the second decade of life, the authors suggested that in the retina, SCAPER does not play a developmental role, but rather is important for photoreceptor function and/or maintenance.
Intellectual disability v2.552 SCAPER Louise Daugherty Phenotypes for gene: SCAPER were changed from AUTOSOMAL RECESSIVE MENTAL RETARDATION to AUTOSOMAL RECESSIVE MENTAL RETARDATION; Intellectual developmental disorder and retinitis pigmentosa, 618195
Genetic epilepsy syndromes v0.1027 PIGO Eleanor Williams Phenotypes for gene: PIGO were changed from to Hyperphosphatasia with mental retardation syndrome 2, 614749
Genetic epilepsy syndromes v0.1026 PIGO Eleanor Williams Added comment: Comment on publications: Further cases reported in PMIDs: 28900819 and 28337824
Genetic epilepsy syndromes v0.1026 PIGO Eleanor Williams Publications for gene: PIGO were set to
Genetic epilepsy syndromes v0.1025 PIGO Eleanor Williams Mode of inheritance for gene: PIGO was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.1024 PIGO Eleanor Williams Classified gene: PIGO as Green List (high evidence)
Genetic epilepsy syndromes v0.1024 PIGO Eleanor Williams Added comment: Comment on list classification: Sufficient cases with compound heterogzyous mutations in PIGO and 3 cases with seizures.
Genetic epilepsy syndromes v0.1024 PIGO Eleanor Williams Gene: pigo has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.1023 PIGO Eleanor Williams commented on gene: PIGO
Genetic epilepsy syndromes v0.1023 LARGE1 Ivone Leong Marked gene: LARGE1 as ready
Genetic epilepsy syndromes v0.1023 LARGE1 Ivone Leong Gene: large1 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v0.1023 LARGE1 Ivone Leong Classified gene: LARGE1 as Amber List (moderate evidence)
Genetic epilepsy syndromes v0.1023 LARGE1 Ivone Leong Added comment: Comment on list classification: Phenotype confirmed by both OMIM and Gene2Phenotype. However, there is only one reported case of a patient with mutations in LARGE1 who also have seizures (PMID: 24709677). Therefore not enough evidence to promote to green status.
Genetic epilepsy syndromes v0.1023 LARGE1 Ivone Leong Gene: large1 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v0.1022 LARGE1 Ivone Leong Publications for gene: LARGE1 were set to
Intellectual disability v2.551 NUDT2 Konstantinos Varvagiannis gene: NUDT2 was added
gene: NUDT2 was added to Intellectual disability. Sources: Literature,Expert Review
Mode of inheritance for gene: NUDT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUDT2 were set to 27431290; 30059600
Phenotypes for gene: NUDT2 were set to Muscular hypotonia; Global developmental delay; Intellectual disability
Penetrance for gene: NUDT2 were set to Complete
Review for gene: NUDT2 was set to AMBER
Added comment: PMID: 27431290 reports briefly on 2 sibs from a consanguineous Saudi family, as part of a cohort of 337 patients investigated for intellectual disability. Both were homozygous for a nonsense NUDT2 mutation [NM_001161.4:c.34C>T or p.Arg12Ter / rs148119952]. The common features included hypotonia, global developmental delay (first words at 2.5 years, sitting at 2-2.5 years,walking achieved by 4 years - valid for both sibs) and intellectual disability. No other candidate variants were found in the exome.

PMID: 30059600 is a further report on 5 individuals from 3 consanguineous families from Saudi Arabia. All presented with low birth weight and height, poor suck, hypotonia, motor and language delay and borderline intelligence. All patients were homozygous for the same nonsense variant (Arg12Ter) which seems to be a founder mutation in Saudi Arabia.

As truncating NUDT2 variants have a combined allele frequency of 0.02% in gnomAD (no homozygotes in the database) the authors comment that most of the other LoF variants observed are in the second - and last - exon of the gene (thus probably escaping NMD) and downstream of its catalytic domain.

As a result this gene can be considered for inclusion in the ID panel probably as amber (single founder mutation - the degree of intellectual disability appears to be more severe in the first report but borderline in the subsequent) or green.
Sources: Literature, Expert Review
Genetic epilepsy syndromes v0.1021 PHGDH Eleanor Williams Marked gene: PHGDH as ready
Genetic epilepsy syndromes v0.1021 PHGDH Eleanor Williams Added comment: Comment when marking as ready: Sufficient cases reported with seizures.
Genetic epilepsy syndromes v0.1021 PHGDH Eleanor Williams Gene: phgdh has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.1021 PHGDH Eleanor Williams Phenotypes for gene: PHGDH were changed from to Phosphoglycerate dehydrogenase deficiency 601815
Genetic epilepsy syndromes v0.1020 PHGDH Eleanor Williams Publications for gene: PHGDH were set to
Genetic epilepsy syndromes v0.1019 PHGDH Eleanor Williams Mode of inheritance for gene: PHGDH was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.1018 PHGDH Eleanor Williams Classified gene: PHGDH as Green List (high evidence)
Genetic epilepsy syndromes v0.1018 PHGDH Eleanor Williams Added comment: Comment on list classification: More than 3 variants associated with the disorder. Patients from 7 families present with seizures.
Genetic epilepsy syndromes v0.1018 PHGDH Eleanor Williams Gene: phgdh has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.1017 PHGDH Eleanor Williams commented on gene: PHGDH
Genetic epilepsy syndromes v0.1017 PDHX Eleanor Williams Marked gene: PDHX as ready
Genetic epilepsy syndromes v0.1017 PDHX Eleanor Williams Added comment: Comment when marking as ready: Sufficient variants to associate with disorder. At least 3 cases where seizures are part of the phenotype.
Genetic epilepsy syndromes v0.1017 PDHX Eleanor Williams Gene: pdhx has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.1017 PDHX Eleanor Williams Phenotypes for gene: PDHX were changed from to Lacticacidemia due to PDX1 deficiency 245349
Genetic epilepsy syndromes v0.1016 PDHX Eleanor Williams Publications for gene: PDHX were set to
Genetic epilepsy syndromes v0.1015 PDHX Eleanor Williams Mode of inheritance for gene: PDHX was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.1014 PDHX Eleanor Williams Classified gene: PDHX as Green List (high evidence)
Genetic epilepsy syndromes v0.1014 PDHX Eleanor Williams Added comment: Comment on list classification: Numerous variants in this gene associated with Lacticacidemia are reported. 3 cases where seizures are part of the phenotype.
Genetic epilepsy syndromes v0.1014 PDHX Eleanor Williams Gene: pdhx has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.1013 PDHX Eleanor Williams commented on gene: PDHX
Pain syndromes v1.3 Ellen McDonagh List of related panels changed from neuropathic pain;Pain channelopathies to neuropathic pain; Pain channelopathies
Genetic epilepsy syndromes v0.1013 GBA Louise Daugherty Marked gene: GBA as ready
Genetic epilepsy syndromes v0.1013 GBA Louise Daugherty Gene: gba has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.1013 PDHA1 Eleanor Williams Marked gene: PDHA1 as ready
Genetic epilepsy syndromes v0.1013 PDHA1 Eleanor Williams Added comment: Comment when marking as ready: Sufficient cases.
Genetic epilepsy syndromes v0.1013 PDHA1 Eleanor Williams Gene: pdha1 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.1013 PDHA1 Eleanor Williams Classified gene: PDHA1 as Green List (high evidence)
Genetic epilepsy syndromes v0.1013 PDHA1 Eleanor Williams Added comment: Comment on list classification: > 3 cases of patients with variants in this gene with Pyruvate dehydrogenase E1-alpha deficiency and with seizures as part of the phenotype.
Genetic epilepsy syndromes v0.1013 PDHA1 Eleanor Williams Gene: pdha1 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.1012 GBA Louise Daugherty Classified gene: GBA as Green List (high evidence)
Genetic epilepsy syndromes v0.1012 GBA Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green. Appropriate phenotype, sufficient cases, and external review comment all support gene-disease association
Genetic epilepsy syndromes v0.1012 GBA Louise Daugherty Gene: gba has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.1011 PDHA1 Eleanor Williams Added comment: Comment on mode of inheritance: Heterozygous mutations seen in females showing phenotype.
Genetic epilepsy syndromes v0.1011 PDHA1 Eleanor Williams Mode of inheritance for gene: PDHA1 was changed from to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Genetic epilepsy syndromes v0.1010 PDHA1 Eleanor Williams Added comment: Comment on phenotypes: Siezures are listed as part of the phenotype for X-LINKED LEIGH SYNDROME, PYRUVATE DEHYDROGENASE E1-ALPHA DEFICIENCY IN FEMALES and INTELLECTUAL DISABILTIY in Gene2Phenotype
Genetic epilepsy syndromes v0.1010 PDHA1 Eleanor Williams Phenotypes for gene: PDHA1 were changed from to Pyruvate dehydrogenase E1-alpha deficiency 312170; X-LINKED LEIGH SYNDROME; PYRUVATE DEHYDROGENASE E1-ALPHA DEFICIENCY IN FEMALES; INTELLECTUAL DISABILTIY
Genetic epilepsy syndromes v0.1009 PDHA1 Eleanor Williams Publications for gene: PDHA1 were set to
Genetic epilepsy syndromes v0.1008 PDHA1 Eleanor Williams commented on gene: PDHA1
Genetic epilepsy syndromes v0.1008 GBA Louise Daugherty Publications for gene: GBA were set to 8929950; 15214004; 12838552; 8829654; 8118460
Genetic epilepsy syndromes v0.1007 LIAS Ivone Leong Mode of inheritance for gene: LIAS was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.1006 LIAS Ivone Leong Phenotypes for gene: LIAS were changed from to Hyperglycinemia, lactic acidosis, and seizures, 614462
Genetic epilepsy syndromes v0.1005 LARGE1 Ivone Leong Mode of inheritance for gene: LARGE1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.1004 LARGE1 Ivone Leong Phenotypes for gene: LARGE1 were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 6, 613154; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 6, 608840
Genetic epilepsy syndromes v0.1003 KRAS Ivone Leong Classified gene: KRAS as Amber List (moderate evidence)
Genetic epilepsy syndromes v0.1003 KRAS Ivone Leong Added comment: Comment on list classification: Cardiofaciocutaneous syndrome 2 was confirmed on both OMIM and Gene2Phenotype. One report (PMID: 16474405) found one proband with a missense variant in the KRAS gene that had seizures, and another study (PMID: 21871821) found 2 unrelated Japanese probands with missense mutations who have seizures. There is not enough evidence to promote the gene.
Genetic epilepsy syndromes v0.1003 KRAS Ivone Leong Gene: kras has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v0.1002 GBA Louise Daugherty Added comment: Comment on publications: Added publications to support upgrading of the gene to Green
Genetic epilepsy syndromes v0.1002 GBA Louise Daugherty Publications for gene: GBA were set to
Genetic epilepsy syndromes v0.1001 KRAS Ivone Leong Publications for gene: KRAS were set to
Genetic epilepsy syndromes v0.1000 KRAS Ivone Leong Added comment: Comment on mode of pathogenicity: Variants cause gain-of-function effects (PMID: 21871821, 23059812).
Genetic epilepsy syndromes v0.1000 KRAS Ivone Leong Mode of pathogenicity for gene: KRAS was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Genetic epilepsy syndromes v0.999 GBA Louise Daugherty Added comment: Comment on mode of inheritance: Added MOI from external clinical review and publications
Genetic epilepsy syndromes v0.999 GBA Louise Daugherty Mode of inheritance for gene: GBA was changed from to BIALLELIC, autosomal or pseudoautosomal
Thoracic aortic aneurysm or dissection v1.77 Ellen McDonagh List of related panels changed from Familial retinal arteriolar tortuosity;FTAAD;Familial Thoracic Aortic Aneurysm Disease to Familial retinal arteriolar tortuosity; FTAAD; Familial Thoracic Aortic Aneurysm Disease
Genetic epilepsy syndromes v0.998 GBA Louise Daugherty Added comment: Comment on phenotypes: Added phenotypes suggested from expert review and reviewed literature that indicate relevance to inclusion on the Genetic Epilepsy Syndromes panel
Genetic epilepsy syndromes v0.998 GBA Louise Daugherty Phenotypes for gene: GBA were changed from to Gaucher disease, perinatal lethal, 608013; Gaucher disease, type II, 230900; Gaucher disease, type III, 231000; Gaucher disease, type IIIC, 231005; seizures
Genetic epilepsy syndromes v0.997 GCH1 Louise Daugherty Marked gene: GCH1 as ready
Genetic epilepsy syndromes v0.997 GCH1 Louise Daugherty Gene: gch1 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.997 GCH1 Louise Daugherty Classified gene: GCH1 as Green List (high evidence)
Genetic epilepsy syndromes v0.997 GCH1 Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green. Appropriate phenotype, sufficient cases, and external review comment all support gene-disease association
Genetic epilepsy syndromes v0.997 GCH1 Louise Daugherty Gene: gch1 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.996 GCH1 Louise Daugherty Mode of inheritance for gene: GCH1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.995 GCH1 Louise Daugherty Added comment: Comment on publications: Added publications to support upgrading of the gene to Green
Genetic epilepsy syndromes v0.995 GCH1 Louise Daugherty Publications for gene: GCH1 were set to
Genetic epilepsy syndromes v0.994 PCCB Eleanor Williams Phenotypes for gene: PCCB were changed from to Propionicacidemia 606054
Genetic epilepsy syndromes v0.993 PCCB Eleanor Williams Publications for gene: PCCB were set to
Genetic epilepsy syndromes v0.992 PCCB Eleanor Williams commented on gene: PCCB
Genetic epilepsy syndromes v0.992 PCCB Eleanor Williams Mode of inheritance for gene: PCCB was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.991 GCH1 Louise Daugherty Added comment: Comment on phenotypes: Added phenotypes suggested from expert review that indicate relevance to inclusion on the Genetic Epilepsy Syndromes panel
Genetic epilepsy syndromes v0.991 GCH1 Louise Daugherty Phenotypes for gene: GCH1 were changed from to Hyperphenylalaninemia, BH4-deficient, B, 233910; seizures
Genetic epilepsy syndromes v0.990 PTS Sarah Leigh Classified gene: PTS as Green List (high evidence)
Genetic epilepsy syndromes v0.990 PTS Sarah Leigh Gene: pts has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.989 PCCB Eleanor Williams commented on gene: PCCB
Genetic epilepsy syndromes v0.989 PTS Sarah Leigh Phenotypes for gene: PTS were changed from to Hyperphenylalaninemia, BH4-deficient, A, 261640
Genetic epilepsy syndromes v0.988 PTS Sarah Leigh Publications for gene: PTS were set to
Genetic epilepsy syndromes v0.987 GFAP Louise Daugherty Marked gene: GFAP as ready
Genetic epilepsy syndromes v0.987 GFAP Louise Daugherty Gene: gfap has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.987 PTS Sarah Leigh Mode of inheritance for gene: PTS was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.986 GFAP Louise Daugherty Classified gene: GFAP as Green List (high evidence)
Genetic epilepsy syndromes v0.986 GFAP Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green. Appropriate phenotype, sufficient cases, and external review comment all support gene-disease association
Genetic epilepsy syndromes v0.986 GFAP Louise Daugherty Gene: gfap has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.985 GFAP Louise Daugherty Mode of inheritance for gene: GFAP was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic epilepsy syndromes v0.984 GFAP Louise Daugherty Phenotypes for gene: GFAP were changed from to Alexander disease, 203450; seizures
Genetic epilepsy syndromes v0.983 GFAP Louise Daugherty Added comment: Comment on publications: Added publications suggested from external expert review to support upgrading of the gene to Green. From OMIM PMID: 12034785 Gorospe et al. (2002) reported 12 genetically confirmed cases of Alexander disease. Seven of the 12 had onset in infancy (range 2-18 months), with seizures being the most common presenting sign, followed by failure to thrive and delayed motor development.
Genetic epilepsy syndromes v0.983 GFAP Louise Daugherty Publications for gene: GFAP were set to
Genetic epilepsy syndromes v0.982 KRAS Ivone Leong Mode of inheritance for gene: KRAS was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v2.551 GFAP Louise Daugherty Publications for gene: GFAP were set to
Genetic epilepsy syndromes v0.981 PCCA Eleanor Williams Publications for gene: PCCA were set to 2213454; 25875215; 30014764
Genetic epilepsy syndromes v0.980 D2HGDH Rebecca Foulger Marked gene: D2HGDH as ready
Genetic epilepsy syndromes v0.980 D2HGDH Rebecca Foulger Gene: d2hgdh has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.980 D2HGDH Rebecca Foulger Phenotypes for gene: D2HGDH were changed from D-2-hydroxyglutaric aciduria, 600721; generalized tonic-clonic seizures; absence seizures; tonic seizures; tonic-clonic seizures; myoclonic seizures, to D-2-hydroxyglutaric aciduria, 600721; generalized tonic-clonic seizures; absence seizures; tonic seizures; tonic-clonic seizures; myoclonic seizures
Genetic epilepsy syndromes v0.979 D2HGDH Rebecca Foulger Phenotypes for gene: D2HGDH were changed from D-2-hydroxyglutaric aciduria, 600721 to D-2-hydroxyglutaric aciduria, 600721; generalized tonic-clonic seizures; absence seizures; tonic seizures; tonic-clonic seizures; myoclonic seizures,
Genetic epilepsy syndromes v0.978 D2HGDH Rebecca Foulger Classified gene: D2HGDH as Green List (high evidence)
Genetic epilepsy syndromes v0.978 D2HGDH Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green. Green review, and as Zornitza reports, epilepsy is a phenotype of D-2-hydroxyglutaric aciduria. Sufficient unrelated epileptic cases from the literature (2 from PMID:15609246 and 1 from PMID:16037974) to support a diagnostic rating.
Genetic epilepsy syndromes v0.978 D2HGDH Rebecca Foulger Gene: d2hgdh has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.977 D2HGDH Rebecca Foulger commented on gene: D2HGDH: Struys et al 2005 (PMID:15609246) report two unrelated patients affected with severe D-2-hydroxyglutaric aciduria and disease-causing variants in D2HGDH. Patient one suffered tonic, tonic-clonic, and myoclonic seizures, and was homozygous for missense variant in D2HGDH (c.1331T-->C; p.Val444Ala). Patient 2 presented with generalized tonic-clonic seizures and infantile spasms amongst her symptoms. She was compound heterozygous for a missense mutation (c.440T-->G; p.Ile147Ser) and a splice-site mutation (IVS1-23A-->G) that resulted in a null allele.
Genetic epilepsy syndromes v0.977 D2HGDH Rebecca Foulger commented on gene: D2HGDH
Genetic epilepsy syndromes v0.977 PCCA Eleanor Williams Phenotypes for gene: PCCA were changed from to Propionicacidemia 606054
Genetic epilepsy syndromes v0.976 PCCA Eleanor Williams Publications for gene: PCCA were set to
Genetic epilepsy syndromes v0.975 PCCA Eleanor Williams Mode of inheritance for gene: PCCA was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.974 PCCA Eleanor Williams commented on gene: PCCA
Genetic epilepsy syndromes v0.974 GLB1 Louise Daugherty Marked gene: GLB1 as ready
Genetic epilepsy syndromes v0.974 GLB1 Louise Daugherty Gene: glb1 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.974 GLB1 Louise Daugherty Classified gene: GLB1 as Green List (high evidence)
Genetic epilepsy syndromes v0.974 GLB1 Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green. Appropriate phenotype, sufficient cases, and external review comment all support gene-disease association
Genetic epilepsy syndromes v0.974 GLB1 Louise Daugherty Gene: glb1 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.973 GLB1 Louise Daugherty Publications for gene: GLB1 were set to
Genetic epilepsy syndromes v0.972 UFM1 Konstantinos Varvagiannis reviewed gene: UFM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28931644, 29868776; Phenotypes: Leukodystrophy hypomyelinating 14, 617899; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.972 UFM1 Konstantinos Varvagiannis Deleted their review
Intellectual disability v2.550 UFM1 Konstantinos Varvagiannis reviewed gene: UFM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28931644, 29868776; Phenotypes: Leukodystrophy hypomyelinating 14, 617899; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v2.550 UFM1 Konstantinos Varvagiannis Deleted their review
Genetic epilepsy syndromes v0.972 UFM1 Konstantinos Varvagiannis gene: UFM1 was added
gene: UFM1 was added to Genetic epilepsy syndromes. Sources: Literature,Expert Review
Mode of inheritance for gene: UFM1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: UFM1 were set to 28931644; 29868776
Phenotypes for gene: UFM1 were set to Leukodystrophy hypomyelinating 14, 617899
Penetrance for gene: UFM1 were set to Complete
Review for gene: UFM1 was set to GREEN
Added comment: Biallelic UFM1 mutations cause Leukodystrophy hypomyelinating 14, MIM 617899.

PMID: 28931644 is the first report on 16 individuals from 14 families with shared Roma ethnic background. All subjects were found to harbor a UFM1 promoter 3 basepair deletion in the homozygous state.

All patients demonstrated a severe phenotype including lack of development and severe epileptic encephalopathy while their MRI images demonstrated hypomyelination with atrophy of the basal ganglia and the cerebellum.

The promoter deletion was detected by exome sequencing. Previously a 0.8 Mb homozygous region (encompassing UFM1) was identified to be shared by all the patients in whom a SNP array was performed. Alternative causes, notably TUBB4A mutations and deletions/duplications were excluded. 3 individuals had Sanger sequencing of all coding regions within the homozygous interval to rule out other - eventually missed - variants.

PMID: 29868776 reports 4 additional individuals from 2 consanguineous families (one from Ethiopia, for the other this was not specified). All 4 patients were homozygous for the c.241C>T (NM_016617.3) or p.(Arg81Cys) variant which was shown to be hypomorphic upon functional studies.

The phenotype consisted of developmental delay (4/4 or 20/20 including the patients from the previous report with which comparison is made in table 2 of the article) with microcephaly (4/4 or 20/20) and seizures (4/4 or 16/20) as well as MRI abnormalities. Failure to thrive and/or short stature were also among the most common features.

UFM1 (as well as UFC1 also discussed in the same article) participate in ufmylation, with mutations in other enzymes of the same process (notably UBA5 - gene rated Green in the ID and epilepsy panels) having already been described in neurodevelopmental disorders.

As a result, this gene can be considered for inclusion in this panel as green (or amber).
Sources: Literature, Expert Review
Genetic epilepsy syndromes v0.972 GLB1 Louise Daugherty Added comment: Comment on phenotypes: Added phenotype suggested from expert review that indicate relevance to inclusion on the Genetic Epilepsy Syndromes panel
Genetic epilepsy syndromes v0.972 GLB1 Louise Daugherty Phenotypes for gene: GLB1 were changed from to GM1-gangliosidosis, type II, 230600; seizures
Intellectual disability v2.550 UFM1 Konstantinos Varvagiannis gene: UFM1 was added
gene: UFM1 was added to Intellectual disability. Sources: Literature,Expert Review
Mode of inheritance for gene: UFM1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: UFM1 were set to 28931644; 29868776
Phenotypes for gene: UFM1 were set to Leukodystrophy hypomyelinating 14, 617899
Penetrance for gene: UFM1 were set to Complete
Review for gene: UFM1 was set to GREEN
Added comment: Biallelic UFM1 mutations cause Leukodystrophy hypomyelinating 14, MIM 617899.

PMID: 28931644 is the first report on 16 individuals from 14 families with shared Roma ethnic background. All subjects were found to harbor a UFM1 promoter 3 basepair deletion in the homozygous state.

All patients demonstrated a severe phenotype including lack of development and severe epileptic encephalopathy while their MRI images demonstrated hypomyelination with atrophy of the basal ganglia and the cerebellum.

The promoter deletion was detected by exome sequencing. Previously a 0.8 Mb homozygous region was identified to be shared by all the patients in whom a SNP array was performed. Alternative causes, notably TUBB4A mutations and deletions/duplications were excluded. 3 individuals had Sanger sequencing of all coding regions within the homozygous interval to rule out other - eventually missed - variants.

PMID: 29868776 reports 4 additional individuals from 2 consanguineous families (one from Ethiopia, for the other this was not specified). All 4 patients were homozygous for the c.241C>T (NM_016617.3) or p.(Arg81Cys) variant which was shown to be hypomorphic upon functional studies.

The phenotype consisted of developmental delay (4/4 or 20/20 including the patients from the previous report with which comparison is made in table 2 of the article) with microcephaly (4/4 or 20/20) and seizures (4/4 or 16/20) as well as MRI abnormalities. Failure to thrive and/or short stature were also among the most common features.

UFM1 (as well as UFC1 also discussed in the same article) participate in ufmylation, with mutations in other enzymes of the same process (notably UBA5 - gene rated Green in the ID and epilepsy panels) having already been described in neurodevelopmental disorders.

As a result, this gene can be considered for inclusion in this panel as green (or amber).
Sources: Literature, Expert Review
Genetic epilepsy syndromes v0.971 GLB1 Louise Daugherty Mode of inheritance for gene: GLB1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.970 D2HGDH Rebecca Foulger Mode of inheritance for gene: D2HGDH was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.969 D2HGDH Rebecca Foulger Phenotypes for gene: D2HGDH were changed from to D-2-hydroxyglutaric aciduria, 600721
Intellectual disability v2.550 GLB1 Louise Daugherty Publications for gene: GLB1 were set to
Short QT syndrome v1.0 Sarah Leigh promoted panel to version 1.0
Genetic epilepsy syndromes v0.968 GLDC Louise Daugherty Marked gene: GLDC as ready
Genetic epilepsy syndromes v0.968 GLDC Louise Daugherty Gene: gldc has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.968 GLDC Louise Daugherty Classified gene: GLDC as Green List (high evidence)
Genetic epilepsy syndromes v0.968 GLDC Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green. Appropriate phenotype, sufficient cases, and external review comment all support gene-disease association
Genetic epilepsy syndromes v0.968 GLDC Louise Daugherty Gene: gldc has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.967 GLDC Louise Daugherty Added comment: Comment on publications: Added publications to support upgrading of the gene to Green
Genetic epilepsy syndromes v0.967 GLDC Louise Daugherty Publications for gene: GLDC were set to
Genetic epilepsy syndromes v0.966 CTSD Rebecca Foulger Marked gene: CTSD as ready
Genetic epilepsy syndromes v0.966 CTSD Rebecca Foulger Gene: ctsd has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.966 CTSD Rebecca Foulger Classified gene: CTSD as Green List (high evidence)
Genetic epilepsy syndromes v0.966 CTSD Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green. Epileptic seizures are an accepted phenotype of CLN10 disease (MIM:610127). Epilepsy reported as part of the symptoms in at least 2 families in literature (PMID:16670177 and PMID:26059544) PLUS animal model of epilepsy (PMID:10995834). Therefore 2 cases + clear animal model is sufficient evidence for diagnostic rating.
Genetic epilepsy syndromes v0.966 CTSD Rebecca Foulger Gene: ctsd has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.965 CTSD Rebecca Foulger commented on gene: CTSD: PMID:26059544 (Meyer et al 2015) report 2 siblings with CLN10 disease who showed intractable seizures and respiratory insufficiency immediately after birth. A homozygous insertion (c.268_269insC) in exon 3 of the cathepsin D gene was found in both infants.
Genetic epilepsy syndromes v0.965 CTSD Rebecca Foulger commented on gene: CTSD: Animal mode: CatD-deficient mice develop seizures and progressive retinal atrophy, becoming blind (See PMIDs:10995834 and 16685649).
Genetic epilepsy syndromes v0.965 CTSD Rebecca Foulger commented on gene: CTSD
Genetic epilepsy syndromes v0.965 CTSD Rebecca Foulger Publications for gene: CTSD were set to
Genetic epilepsy syndromes v0.964 KRAS Ivone Leong Phenotypes for gene: KRAS were changed from to Cardiofaciocutaneous syndrome 2, 615278
Genetic epilepsy syndromes v0.963 KIF5C Ivone Leong Classified gene: KIF5C as Green List (high evidence)
Genetic epilepsy syndromes v0.963 KIF5C Ivone Leong Added comment: Comment on list classification: Promoted from amber to green. Phenotype is confirmed in both OMIM and Gene2Phenotype.
There are 3 studies (PMID: 23603762, 23033978, 29048727) that have reported, in total, 3 unrelated families (5 patients) who have various missense variants in this gene who have Cortical dysplasia and also seizures.
Genetic epilepsy syndromes v0.963 KIF5C Ivone Leong Gene: kif5c has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.962 GLDC Louise Daugherty Mode of inheritance for gene: GLDC was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.961 GLDC Louise Daugherty Added comment: Comment on phenotypes: Added phenotypes suggested from expert review that indicate relevance to inclusion on the Genetic Epilepsy Syndromes panel
Genetic epilepsy syndromes v0.961 GLDC Louise Daugherty Phenotypes for gene: GLDC were changed from to Glycine encephalopathy, 605899; seizures
Genetic epilepsy syndromes v0.960 KIF5C Ivone Leong Publications for gene: KIF5C were set to
Genetic epilepsy syndromes v0.959 GLUD1 Louise Daugherty Marked gene: GLUD1 as ready
Genetic epilepsy syndromes v0.959 GLUD1 Louise Daugherty Gene: glud1 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.959 GLUD1 Louise Daugherty Classified gene: GLUD1 as Green List (high evidence)
Genetic epilepsy syndromes v0.959 GLUD1 Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green. Appropriate phenotype, sufficient cases, and external review comment all support gene-disease association.
Genetic epilepsy syndromes v0.959 GLUD1 Louise Daugherty Gene: glud1 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.958 GLUD1 Louise Daugherty Phenotypes for gene: GLUD1 were changed from Hyperinsulinism-hyperammonemia syndrome, 606762 to Hyperinsulinism-hyperammonemia syndrome, 606762; epilepsy
Genetic epilepsy syndromes v0.957 GLUD1 Louise Daugherty Publications for gene: GLUD1 were set to 19046187
Genetic epilepsy syndromes v0.956 CTSD Rebecca Foulger Mode of inheritance for gene: CTSD was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.955 CTSD Rebecca Foulger Phenotypes for gene: CTSD were changed from to Ceroid lipofuscinosis, neuronal, 10, 610127
Genetic epilepsy syndromes v0.954 GLUL Louise Daugherty Marked gene: GLUL as ready
Genetic epilepsy syndromes v0.954 GLUL Louise Daugherty Gene: glul has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.954 GLUL Louise Daugherty Added comment: Comment on publications: Added publications to support upgrading of the gene to Green
Genetic epilepsy syndromes v0.954 GLUL Louise Daugherty Publications for gene: GLUL were set to
Genetic epilepsy syndromes v0.953 GLUL Louise Daugherty Classified gene: GLUL as Green List (high evidence)
Genetic epilepsy syndromes v0.953 GLUL Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green. Appropriate phenotype, sufficient cases, and external review comment all support gene-disease association.
Genetic epilepsy syndromes v0.953 GLUL Louise Daugherty Gene: glul has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.952 KIF5C Ivone Leong Mode of inheritance for gene: KIF5C was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic epilepsy syndromes v0.951 KIF5C Ivone Leong Phenotypes for gene: KIF5C were changed from to Cortical dysplasia, complex, with other brain malformations 2, 615282
Intellectual disability v2.549 CSNK2B Rebecca Foulger Phenotypes for gene: CSNK2B were changed from to Intellectual disability with or without myoclonic epilepsy
Genetic epilepsy syndromes v0.950 KCTD3 Ivone Leong Marked gene: KCTD3 as ready
Genetic epilepsy syndromes v0.950 KCTD3 Ivone Leong Gene: kctd3 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.950 KCTD3 Ivone Leong Classified gene: KCTD3 as Green List (high evidence)
Genetic epilepsy syndromes v0.950 KCTD3 Ivone Leong Added comment: Comment on list classification: Promoted from amber to green. No phenotypes are associated with this gene OMIM or Gene2Phenotype.
One study (PMID: 29406573) reported various mutations in this gene for 7 probands from 4 consanguineous families who all have epilepsy. The families are from the same geographical location. The study did show that the variants segregated with the phenotype. Two other large (PMID: 27848944, 25558065) screening studies reported 3 probands with frameshift variants in this gene who have epilepsy.
Genetic epilepsy syndromes v0.950 KCTD3 Ivone Leong Gene: kctd3 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.949 GLUD1 Louise Daugherty Added comment: Comment on phenotypes: Added phenotypes suggested from expert review that indicate relevance to inclusion on the Genetic Epilepsy Syndromes panel
Genetic epilepsy syndromes v0.949 GLUD1 Louise Daugherty Phenotypes for gene: GLUD1 were changed from to Hyperinsulinism-hyperammonemia syndrome, 606762
Intellectual disability v2.548 CSNK2B Rebecca Foulger Publications for gene: CSNK2B were set to 28585349, 28762608
Genetic epilepsy syndromes v0.948 GLUD1 Louise Daugherty Added comment: Comment on publications: Added publications suggested from external expert review to support upgrading of the gene to Green
Genetic epilepsy syndromes v0.948 GLUD1 Louise Daugherty Publications for gene: GLUD1 were set to
Genetic epilepsy syndromes v0.947 GLUD1 Louise Daugherty Added comment: Comment on mode of inheritance: Changed MOI from external clinical review and publications
Genetic epilepsy syndromes v0.947 GLUD1 Louise Daugherty Mode of inheritance for gene: GLUD1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v2.547 CSNK2B Rebecca Foulger Classified gene: CSNK2B as Green List (high evidence)
Intellectual disability v2.547 CSNK2B Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Green: As summarised by Zornitza, three unrelated patients reported in the literature (one in PMID:28762608 and two in PMID:28585349) with intellectual disability and de novo variants in CSNK2B (splice variant and a frameshift truncating variant). Two of the patients also had monoclonic epilepsy.
Intellectual disability v2.547 CSNK2B Rebecca Foulger Gene: csnk2b has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.946 KCTD3 Ivone Leong Phenotypes for gene: KCTD3 were changed from to No OMIM number; Epileptic encephalopathy
Intellectual disability v2.546 CSNK2B Rebecca Foulger Mode of inheritance for gene: CSNK2B was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic epilepsy syndromes v0.945 KCTD3 Ivone Leong Publications for gene: KCTD3 were set to
Genetic epilepsy syndromes v0.944 KCTD3 Ivone Leong Mode of inheritance for gene: KCTD3 was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.943 UFC1 Konstantinos Varvagiannis gene: UFC1 was added
gene: UFC1 was added to Genetic epilepsy syndromes. Sources: Literature,Expert Review
Mode of inheritance for gene: UFC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UFC1 were set to 29868776
Phenotypes for gene: UFC1 were set to Neurodevelopmental disorder with spasticity and poor growth, 618076
Penetrance for gene: UFC1 were set to Complete
Review for gene: UFC1 was set to GREEN
Added comment: Biallelic UFC1 mutations cause Neurodevelopmental disorder with spasticity and poor growth, MIM 618076.

PMID: 29868776 describes 7 individuals (most) born to consanguineous Saudi families (in one case the parents were not consanguineous but originated from the same tribe) as well as a further individual born to distantly related Swiss parents. One of these patients was previously briefly published by the same authors (PMID: 27431290).

The phenotype consisted of developmental delay (8/8 - usually profound), failure to thrive (8/8), short stature and microcephaly (both observed in 7/8), seizures (4/8) and variable brain MRI anomalies in some of these subjects.

Overall, two UFC1 missense variants are reported [NM_016406.3:c.317C>T or p.(Thr106Ile) and c.68G>A or p.(Arg23Gln) the former in the Saudi individuals]. Functional studies demonstrated the hypomorphic nature of the variants.

UFC1 (as well as UFM1 also discussed in the same article) participate in ufmylation, with mutations in other enzymes of the same process (notably UBA5 - gene rated Green in the ID and epilepsy panels) having already been described in neurodevelopmental disorders.

Epilepsy was a feature in 50% (4/8) of the individuals reported.

As a result this gene can be considered for inclusion in the epilepsy panel as green (or amber).
Sources: Literature, Expert Review
Intellectual disability v2.545 UFC1 Konstantinos Varvagiannis gene: UFC1 was added
gene: UFC1 was added to Intellectual disability. Sources: Literature,Expert Review
Mode of inheritance for gene: UFC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UFC1 were set to 29868776
Phenotypes for gene: UFC1 were set to Neurodevelopmental disorder with spasticity and poor growth, 618076
Penetrance for gene: UFC1 were set to Complete
Review for gene: UFC1 was set to GREEN
Added comment: Biallelic UFC1 mutations cause Neurodevelopmental disorder with spasticity and poor growth, MIM 618076.

PMID: 29868776 describes 7 individuals (most) born to consanguineous Saudi families (in one case the parents were not consanguineous but originated from the same tribe) as well as a further individual born to distantly related Swiss parents. One of these patients was previously briefly published by the same authors (PMID: 27431290).

The phenotype consisted of developmental delay (8/8 - usually profound), failure to thrive (8/8), short stature and microcephaly (both observed in 7/8), seizures (4/8) and variable brain MRI anomalies in some of these subjects.

Overall, two UFC1 missense variants are reported [NM_016406.3:c.317C>T or p.(Thr106Ile) and c.68G>A or p.(Arg23Gln) the former in the Saudi individuals]. Functional studies demonstrated the hypomorphic nature of the variants.

UFC1 (as well as UFM1 also discussed in the same article) participate in ufmylation, with mutations in other enzymes of the same process (notably UBA5 - gene rated Green in the ID and epilepsy panels) having already been described in neurodevelopmental disorders.

As a result this gene can be considered for inclusion in the ID panel as green (or amber).
Sources: Literature, Expert Review
Genetic epilepsy syndromes v0.943 KCNQ5 Ivone Leong Marked gene: KCNQ5 as ready
Genetic epilepsy syndromes v0.943 KCNQ5 Ivone Leong Added comment: Comment when marking as ready: Phenotype conformed on OMIM and Gene2Phenotype. KCNQ5 is a green gene on the Intellectual disability panel.

As stated by Zornitza Stark (Australian Genomics), the original paper (PMID: 28669405) describes 2 of 4 patients with variants in this gene who have seizures (both are are South East Asian decent). Another paper (PMID: 30359776) describes a patient with an intragenic duplication variant in this gene who has seizures. However, as there's just not quit nough evidence I have put the Watchlist tag on.
Genetic epilepsy syndromes v0.943 KCNQ5 Ivone Leong Gene: kcnq5 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v0.943 KCNQ5 Ivone Leong Tag watchlist tag was added to gene: KCNQ5.
Genetic epilepsy syndromes v0.943 CSNK2B Rebecca Foulger Marked gene: CSNK2B as ready
Genetic epilepsy syndromes v0.943 CSNK2B Rebecca Foulger Added comment: Comment when marking as ready: Marked as Ready: November 19th 2018.
Genetic epilepsy syndromes v0.943 CSNK2B Rebecca Foulger Gene: csnk2b has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v0.943 CSNK2B Rebecca Foulger commented on gene: CSNK2B: Added watchlist tag.
Genetic epilepsy syndromes v0.943 CSNK2B Rebecca Foulger Tag watchlist tag was added to gene: CSNK2B.
Genetic epilepsy syndromes v0.943 CSNK2B Rebecca Foulger Classified gene: CSNK2B as Amber List (moderate evidence)
Genetic epilepsy syndromes v0.943 CSNK2B Rebecca Foulger Added comment: Comment on list classification: Kept rating as Amber: As summarised by Zornitza, currently 2 epileptic patients with de novo CSNK2B variants (PMID:28762608 and PMID:28585349). The third patient was reported with intellectual disability but not epilepsy. At least one further epileptic case required for diagnostic rating.
Genetic epilepsy syndromes v0.943 CSNK2B Rebecca Foulger Gene: csnk2b has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v0.942 CSNK2B Rebecca Foulger commented on gene: CSNK2B
Genetic epilepsy syndromes v0.942 CSNK2B Rebecca Foulger Phenotypes for gene: CSNK2B were changed from to Myoclonic epilepsy and intellectual disability
Genetic epilepsy syndromes v0.941 CSNK2B Rebecca Foulger Publications for gene: CSNK2B were set to
Genetic epilepsy syndromes v0.940 CSNK2B Rebecca Foulger Mode of inheritance for gene: CSNK2B was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic epilepsy syndromes v0.939 KCNQ5 Ivone Leong Publications for gene: KCNQ5 were set to
Genetic epilepsy syndromes v0.938 KCNQ5 Ivone Leong Mode of inheritance for gene: KCNQ5 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic epilepsy syndromes v0.937 KCNQ5 Ivone Leong Phenotypes for gene: KCNQ5 were changed from to Mental retardation, autosomal dominant 46, 617601
Genetic epilepsy syndromes v0.936 KCNJ11 Ivone Leong Classified gene: KCNJ11 as Green List (high evidence)
Genetic epilepsy syndromes v0.936 KCNJ11 Ivone Leong Added comment: Comment on list classification: Promoted from amber to green. Conformed for Diabetes, permanent neonatal, with or without neurologic features (PNDM) on OMIM but not on Gene2Phenotype, which lists only Diabetes mellitus, kcnj11-related transient neonatal. It should be noted that in the OMIM (606176), developmental delay, epilepsy, and neonatal diabetes (DEND) is also included, which is a more severe form of the disease.
KCNJ11 is also a green gene in the Intellectual disability gene panel.
There are 4 studies (PMID: 25678012,
16670688,16609879,27681997) describing, in total, 27 unrelated probands with DEND or PNDM who have seizures.
Genetic epilepsy syndromes v0.936 KCNJ11 Ivone Leong Gene: kcnj11 has been classified as Green List (High Evidence).
Dilated cardiomyopathy - teen and adult v1.37 PPP1R13L Louise Daugherty Classified gene: PPP1R13L as Green List (high evidence)
Dilated cardiomyopathy - teen and adult v1.37 PPP1R13L Louise Daugherty Added comment: Comment on list classification: Changed from Red to Green. Appropriate phenotypes, sufficient cases, and external review comment denoting extra cases and evidences all support gene-disease association.
Dilated cardiomyopathy - teen and adult v1.37 PPP1R13L Louise Daugherty Gene: ppp1r13l has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.935 KCNJ11 Ivone Leong Publications for gene: KCNJ11 were set to
Genetic epilepsy syndromes v0.934 KCNJ11 Ivone Leong Added comment: Comment on mode of pathogenicity: Gain-of-function mutations are responsible for the phenotype (PMID: 17065345).
Genetic epilepsy syndromes v0.934 KCNJ11 Ivone Leong Mode of pathogenicity for gene: KCNJ11 was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Dilated cardiomyopathy - teen and adult v1.36 PPP1R13L Louise Daugherty Added comment: Comment on publications: Added publications suggested from external expert review to support upgrading of the gene to Green
Dilated cardiomyopathy - teen and adult v1.36 PPP1R13L Louise Daugherty Publications for gene: PPP1R13L were set to 28069640; 25691752; 19016676
Genetic epilepsy syndromes v0.933 KCNJ11 Ivone Leong Mode of inheritance for gene: KCNJ11 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic epilepsy syndromes v0.932 CCDC88A Konstantinos Varvagiannis reviewed gene: CCDC88A: Rating: AMBER; Mode of pathogenicity: None; Publications: 26917597, 30392057; Phenotypes: ; Mode of inheritance: None
Intellectual disability v2.545 CCDC88A Konstantinos Varvagiannis reviewed gene: CCDC88A: Rating: AMBER; Mode of pathogenicity: None; Publications: 26917597, 30392057; Phenotypes: ?PEHO syndrome-like, 617507; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v2.545 EIF3F Louise Daugherty Classified gene: EIF3F as Green List (high evidence)
Intellectual disability v2.545 EIF3F Louise Daugherty Added comment: Comment on list classification: New gene added by external expert and reviewed by curation team, enough evidence to support gene-disease association and relevance to this panel to rate this gene Green
Intellectual disability v2.545 EIF3F Louise Daugherty Gene: eif3f has been classified as Green List (High Evidence).
Arthrogryposis - broad panel v0.4 Ellen McDonagh List of related panels changed from to Arthrogryposis; GMS R83
White matter disorders - childhood onset v0.6 Ellen McDonagh List of related panels changed from to Childhood onset leukodystrophy; GMS R109
Cerebral malformations v0.5 Ellen McDonagh List of related panels changed from to Cerebral malformation; GMS R87
Hypotonic infant v0.6 Ellen McDonagh List of related panels changed from to Floppy infant with a likely central cause; GMS R69
Epilepsy - early onset or syndromic v0.289 Ellen McDonagh List of related panels changed from to Early onset or syndromic epilepsy; GMS R59
Hereditary ataxia and cerebellar anomalies - childhood onset v0.5 Ellen McDonagh List of related panels changed from Hereditary ataxia with onset in childhood; GMS R55 to Hereditary ataxia with onset in childhood; GMS R55; Cerebellar anomalies; GMS R84
Hereditary ataxia and cerebellar anomalies - childhood onset v0.4 Ellen McDonagh List of related panels changed from to Hereditary ataxia with onset in childhood; GMS R55
Intellectual disability v2.544 RHOBTB2 Louise Daugherty Classified gene: RHOBTB2 as Green List (high evidence)
Intellectual disability v2.544 RHOBTB2 Louise Daugherty Added comment: Comment on list classification: New gene added by external expert and reviewed by curation team, enough evidence to support gene-disease association and relevance to this panel to rate this gene Green
Intellectual disability v2.544 RHOBTB2 Louise Daugherty Gene: rhobtb2 has been classified as Green List (High Evidence).
Cystic renal disease v0.6 Ellen McDonagh List of related panels changed from to Cystic renal disease - PKD1; GMS R193
Paediatric disorders v0.8 Ellen McDonagh List of related panels changed from Acutely unwell children with a likely monogenic disorder; GMS R14 to Acutely unwell children with a likely monogenic disorder; GMS R14; Congenital malformation and dysmorphism syndromes - microarray and sequencing; GMS R27
Paediatric disorders v0.7 Ellen McDonagh List of related panels changed from to Acutely unwell children with a likely monogenic disorder; GMS R14
Inborn errors of metabolism v0.1 Ellen McDonagh List of related panels changed from to Likely inborn error of metabolism - targeted testing not possible; GMS R98
Intellectual disability v2.543 RHOBTB2 Louise Daugherty Added comment: Comment on phenotypes: Added phenotypes suggested from expert review that indicate relevance to inclusion on the Intellectual disability panel
Intellectual disability v2.543 RHOBTB2 Louise Daugherty Phenotypes for gene: RHOBTB2 were changed from Global developmental delay; Intellectual disability; Seizures; Postnatal microcephaly to Epileptic encephalopathy, early infantile, 64, 618004; Global developmental delay; Intellectual disability; Seizures; Postnatal microcephaly
Hereditary ataxia - adult onset v0.1 Ellen McDonagh List of related panels changed from to Hereditary ataxia with onset in adulthood; GMS R54
Neuromuscular disorders v0.2 Ellen McDonagh List of related panels changed from to Other rare neuromuscular disorders; GMS R381
Skeletal dysplasia v1.129 Ellen McDonagh List of related panels changed from Unexplained skeletal dysplasia to Unexplained skeletal dysplasia; Skeletal dysplasia; GMS R104
Intellectual disability v2.542 Ellen McDonagh 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 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; GMS R29
Genetic epilepsy syndromes v0.932 KCNJ11 Ivone Leong Phenotypes for gene: KCNJ11 were changed from Diabetes, permanent neonatal, with or without neurologic features, 606176 to Diabetes, permanent neonatal, with or without neurologic features, 606176; DEND syndrome
Diabetes - neonatal onset v1.9 Ellen McDonagh List of related panels changed from Neonatal diabetes (diagnosed less than 6 months);Neonatal diabetes;Neonatal diabetes diagnosed <6 months to Neonatal diabetes (diagnosed less than 6 months); Neonatal diabetes; Neonatal diabetes diagnosed <6 months; GMS R143
Intellectual disability v2.542 RHOBTB2 Louise Daugherty commented on gene: RHOBTB2
Hydrocephalus v1.24 Ellen McDonagh List of related panels changed from to Hydrocephalus; GMS R86
Craniosynostosis v1.42 Ellen McDonagh List of related panels changed from Craniosynostosis syndromes;Craniosynostosis syndromes phenotypes to Craniosynostosis syndromes; Craniosynostosis syndromes phenotypes; Rare syndromic craniosynostosis or isolated multisuture synostosis; GMS R100
Hereditary spastic paraplegia - childhood onset v0.2 Ellen McDonagh List of related panels changed from to Childhood onset hereditary spastic paraplegia; GMS R61
Congenital disorders of glycosylation v1.20 FUT8 Louise Daugherty Classified gene: FUT8 as Green List (high evidence)
Congenital disorders of glycosylation v1.20 FUT8 Louise Daugherty Added comment: Comment on list classification: New gene added by external expert and reviewed by curation team, enough evidence to support gene-disease association and relevance to this panel to rate this gene Green
Congenital disorders of glycosylation v1.20 FUT8 Louise Daugherty Gene: fut8 has been classified as Green List (High Evidence).
Severe microcephaly v1.39 Ellen McDonagh List of related panels changed from Primary Microcephaly - Microcephalic Dwarfism Spectrum to Primary Microcephaly - Microcephalic Dwarfism Spectrum; Severe microcephaly; GMS R88
Holoprosencephaly v1.6 Ellen McDonagh List of related panels changed from Rhombencephalosynapsis to Rhombencephalosynapsis; Holoprosencephaly - NOT chromosomal; GMS R85
Intellectual disability v2.541 FUT8 Louise Daugherty Classified gene: FUT8 as Green List (high evidence)
Intellectual disability v2.541 FUT8 Louise Daugherty Added comment: Comment on list classification: New gene added by external expert and reviewed by curation team, enough evidence to support gene-disease association and relevance to this panel to rate this gene Green
Intellectual disability v2.541 FUT8 Louise Daugherty Gene: fut8 has been classified as Green List (High Evidence).
Intellectual disability v2.540 FUT8 Louise Daugherty Added comment: Comment on phenotypes: Added phenotypes suggested from expert review that indicate relevance to inclusion on the intellectual disability panel
Intellectual disability v2.540 FUT8 Louise Daugherty Phenotypes for gene: FUT8 were changed from Congenital disorder of glycosylation with defective fucosylation, 618005 to Congenital disorder of glycosylation with defective fucosylation, 618005; Intellectual disability
Intellectual disability v2.539 FUT8 Louise Daugherty Publications for gene: FUT8 were set to 29304374
Genetic epilepsy syndromes v0.931 FUT8 Louise Daugherty Added comment: Comment on phenotypes: Added phenotypes suggested from expert review that indicate relevance to inclusion on the Intellectual Disability panel
Genetic epilepsy syndromes v0.931 FUT8 Louise Daugherty Phenotypes for gene: FUT8 were changed from Congenital disorder of glycosylation with defective fucosylation, 618005 to Congenital disorder of glycosylation with defective fucosylation, 618005; Intellectual disability
Short QT syndrome v0.35 KCNQ1 Sarah Leigh Phenotypes for gene: KCNQ1 were changed from b; Idiopathic Ventricular Fibrillation; Short QT-interval syndrome; Short QT syndrome 2 609621 to Idiopathic Ventricular Fibrillation; Short QT-interval syndrome; Short QT syndrome 2 609621
Short QT syndrome v0.34 CACNA2D1 Sarah Leigh Classified gene: CACNA2D1 as Amber List (moderate evidence)
Short QT syndrome v0.34 CACNA2D1 Sarah Leigh Gene: cacna2d1 has been classified as Amber List (Moderate Evidence).
Short QT syndrome v0.33 CACNA2D1 Sarah Leigh Tag watchlist tag was added to gene: CACNA2D1.
Short QT syndrome v0.33 CACNA2D1 Sarah Leigh Classified gene: CACNA2D1 as Amber List (moderate evidence)
Short QT syndrome v0.33 CACNA2D1 Sarah Leigh Added comment: Comment on list classification: Taking into consideration the Expert review green, this gene is rated amber rather than red, awaiting further reports of Short QT syndrome 6.
Short QT syndrome v0.33 CACNA2D1 Sarah Leigh Gene: cacna2d1 has been classified as Amber List (Moderate Evidence).
Insulin resistance (including lipodystrophy) v1.4 Ellen McDonagh Panel name changed from Insulin resistance (including lipodystrophy to Insulin resistance (including lipodystrophy)
List of related panels changed from Insulin resistance (including lipodystrophy); Insulin resistance (including lipodystrophy to Insulin resistance (including lipodystrophy
Hereditary spastic paraplegia - childhood onset v0.1 Ellen McDonagh Panel status changed from internal to public
Hereditary spastic paraplegia - childhood onset v0.0 Ellen McDonagh Added Panel Hereditary spastic paraplegia - childhood onset
Set panel types to: GMS Rare Disease Virtual
Short QT syndrome v0.32 CACNB2 Sarah Leigh Marked gene: CACNB2 as ready
Short QT syndrome v0.32 CACNB2 Sarah Leigh Gene: cacnb2 has been classified as Amber List (Moderate Evidence).
Hereditary spastic paraplegia v1.71 Ellen McDonagh Panel name changed from Hereditary spastic paraplegia - childhood onset to Hereditary spastic paraplegia
List of related panels changed from Hereditary spastic paraplegia to
Panel types changed to Rare Disease 100K
Short QT syndrome v0.32 CACNB2 Sarah Leigh Tag watchlist tag was added to gene: CACNB2.
Short QT syndrome v0.32 CACNB2 Sarah Leigh Classified gene: CACNB2 as Amber List (moderate evidence)
Short QT syndrome v0.32 CACNB2 Sarah Leigh Added comment: Comment on list classification: Taking into consideration the Expert review green, this gene is rated amber rather than red, awaiting further reports of Short QT syndrome 5 associated with Brugada syndrome 4.
Short QT syndrome v0.32 CACNB2 Sarah Leigh Gene: cacnb2 has been classified as Amber List (Moderate Evidence).
Short QT syndrome v0.31 CACNB2 Sarah Leigh Classified gene: CACNB2 as Amber List (moderate evidence)
Short QT syndrome v0.31 CACNB2 Sarah Leigh Gene: cacnb2 has been classified as Amber List (Moderate Evidence).
White matter disorders - childhood onset v0.5 Ellen McDonagh Panel types changed to GMS Rare Disease Virtual; Super Panel
White matter disorders and cerebral calcification - narrow panel v0.7 Ellen McDonagh Panel types changed to
Monogenic nephrogenic diabetes insipidus v1.8 Ellen McDonagh Panel types changed to Rare Disease 100K
Short QT syndrome v0.30 KCNJ2 Louise Daugherty Publications for gene: KCNJ2 were set to PMID: 15761194; 22155372; 23440193; 24794859; 22311718; 22308236; 19285083; 19710529; 25691870
Short QT syndrome v0.29 KCNQ1 Louise Daugherty Added comment: Comment on publications: Added publications suggested from external expert review to support upgrading of the gene to Green
Short QT syndrome v0.29 KCNQ1 Louise Daugherty Publications for gene: KCNQ1 were set to 15159330
Short QT syndrome v0.27 KCNJ8 Louise Daugherty Publications for gene: KCNJ8 were set to 21383000; 15569843; 27283775
Short QT syndrome v0.26 CACNB2 Louise Daugherty Publications for gene: CACNB2 were set to PMID: 17224476; 30027834; 29759541
Short QT syndrome v0.25 KCNH2 Louise Daugherty Publications for gene: KCNH2 were set to PMID:14676148; 15828882; 19340359; 18692916; 21130771; 25974115; 29016797; 29759541; 16011830; 19439805; 22194679; 16039272; 29085299
Arthrogryposis v2.31 Ellen McDonagh Panel types changed to Rare Disease 100K
Short QT syndrome v0.24 KCNJ8 Louise Daugherty Publications for gene: KCNJ8 were set to PMID: 21383000; 15569843; 27283775
Short QT syndrome v0.23 CACNA1C Louise Daugherty Added comment: Comment on publications: removed inclusion of PMID
Short QT syndrome v0.23 CACNA1C Louise Daugherty Publications for gene: CACNA1C were set to PMID: 17224476; 28427417; 28490369; 29759541; 29697308
Short QT syndrome v0.22 SCN5A Sarah Leigh Classified gene: SCN5A as Amber List (moderate evidence)
Short QT syndrome v0.22 SCN5A Sarah Leigh Added comment: Comment on list classification: Although this gene has been given an Expert review Green, to date there is only one case reported with short QT, hence the "watchlist" tag has been added and an Amber rating has been assigned.
Short QT syndrome v0.22 SCN5A Sarah Leigh Gene: scn5a has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v0.930 KCNJ11 Ivone Leong Phenotypes for gene: KCNJ11 were changed from to Diabetes, permanent neonatal, with or without neurologic features, 606176
Short QT syndrome v0.20 PKP2 Sarah Leigh Publications for gene: PKP2 were set to 24352520; 26888179
Genetic epilepsy syndromes v0.929 ISPD Ivone Leong Marked gene: ISPD as ready
Genetic epilepsy syndromes v0.929 ISPD Ivone Leong Added comment: Comment when marking as ready: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7 confirmed on OMIM but listed as Walker-Warburg syndrome, which comes under Muscular dystrophy-dystroglycanopathy, on Gene2Phenotype. Only one report of a patient with a large deletion in the ISPD gene having seizures (24120487).
Genetic epilepsy syndromes v0.929 ISPD Ivone Leong Gene: ispd has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v0.929 ISPD Ivone Leong Publications for gene: ISPD were set to
Intellectual disability v2.538 ATP6V1A Louise Daugherty Classified gene: ATP6V1A as Green List (high evidence)
Intellectual disability v2.538 ATP6V1A Louise Daugherty Added comment: Comment on list classification: New gene added by external expert and reviewed by curation team, enough evidence to support gene-disease association and relevance to this panel to rate this gene Green
Intellectual disability v2.538 ATP6V1A Louise Daugherty Gene: atp6v1a has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.928 ISPD Ivone Leong Phenotypes for gene: ISPD were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7, 614643 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7, 614643; Walker-Warburg syndrome
Genetic epilepsy syndromes v0.927 GNB5 Konstantinos Varvagiannis gene: GNB5 was added
gene: GNB5 was added to Genetic epilepsy syndromes. Sources: Literature,Expert Review
Mode of inheritance for gene: GNB5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GNB5 were set to 27523599; 27677260; 28697420; 29368331
Phenotypes for gene: GNB5 were set to Intellectual developmental disorder with cardiac arrhythmia, 617173; Language delay and ADHD/cognitive impairment with or without cardiac arrhythmia, 617182
Penetrance for gene: GNB5 were set to Complete
Review for gene: GNB5 was set to GREEN
Added comment: Biallelic GNB5 pathogenic variants cause Intellectual developmental disorder with cardiac arrhythmia (MIM 617173) or language delay and ADHD/cognitive impairment with or without cardiac arrhythmia (MIM 617182).

PMID: 27523599 is the first report on the associated phenotype. A total of 9 individuals from 6 different families (from various ethnic backgrounds) are described.

The common features included hypotonia (noted in 6 out of 9 patients), intellectual disability (9/9 - in 3 cases mild, in 6 severe), heart rate disturbance (9/9 - in most cases sick sinus syndrome), seizures (4/9), ophthalmological problems (nystagmus in 6 out of 7 for whom this information was available) as well as gastric problems (5/8 with G-E reflux).

The 6 variants (summarized in table S1) included : 2 nonsense mutations, 1 synonymous (demonstrated to affect splicing and leading to retention of 25 intronic bp), 2 further splice variants (positions +1 and +3) and a missense one (S81L).

Nonsense mediated decay was the case for the product of the synonymous/splice variant as well as for a stopgain one.

As noted by the authors, individuals homozygous for the S81L variant had a less severe phenotype - among others - with mild degree of intellectual disability.

Functional studies included knockout of gnb5 in zebrafish, which was able to reproduce the human neurological, cardiac and ophthalmological phenotypes.

Alternative causes for these phenotypes (incl. chromosomal or metabolic disorders) were ruled out.

Affected individuals might benefit interventions for their heart rate disturbance as appears to be the case in the article as well as subsequent studies.

PMID: 27677260 describes an extended consanguineous Saudi family with 5 individuals homozygous for the S81L variant. Common features included severe language delay, ADHD, but normal cognition in those available for evaluation. Seizures were not reported. Pathogenicity of the S81L variant is further supported by functional studies.

PMID: 28697420 describes in detail 2 individuals from a large consanguineous pedigree confirmed to be homozygous for a single nucleotide deletion in GNB5. The phenotype included severe DD/ID, seizures, sinus bradycardia with frequent sinus pauses and ophthalmological problems. Sinus arrhythmia and or seizures were documented in several other relatives deceased and unavailable for testing.

PMID: 28327206 reports on 2 subjects previously included in PMID: 27523599.

PMID: 29368331 describes a child with severe developmental delay, nystagmus and sinus arrhythmia necessitating a pacemaker. EEG was abnormal although no frank seizures were observed. The child was compound heterozygous for a novel missense variant (R246Q) as well a 5 basepair deletion.

Epilepsy was a feature in at least 6 individuals reported.

As a result this gene can be considered for inclusion in this panel as green or amber.
Sources: Literature, Expert Review
Intellectual disability v2.537 GNB5 Konstantinos Varvagiannis gene: GNB5 was added
gene: GNB5 was added to Intellectual disability. Sources: Literature,Expert Review
Mode of inheritance for gene: GNB5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GNB5 were set to 27523599; 27677260; 28697420; 29368331
Phenotypes for gene: GNB5 were set to Intellectual developmental disorder with cardiac arrhythmia, 617173; Language delay and ADHD/cognitive impairment with or without cardiac arrhythmia, 617182
Penetrance for gene: GNB5 were set to Complete
Review for gene: GNB5 was set to GREEN
gene: GNB5 was marked as current diagnostic
Added comment: Biallelic GNB5 pathogenic variants cause Intellectual developmental disorder with cardiac arrhythmia (MIM 617173) or language delay and ADHD/cognitive impairment with or without cardiac arrhythmia (MIM 617182).

PMID: 27523599 is the first report on the associated phenotype. A total of 9 individuals from 6 different families (from various ethnic backgrounds) are described.

The common features included hypotonia (noted in 6 out of 9 patients), intellectual disability (9/9 - in 3 cases mild, in 6 severe), heart rate disturbance (9/9 - in most cases sick sinus syndrome), seizures (4/9), ophthalmological problems (nystagmus in 6 out of 7 for whom this information was available) as well as gastric problems (5/8 with G-E reflux).

The 6 variants (summarized in table S1) included : 2 nonsense mutations, 1 synonymous (demonstrated to affect splicing and leading to retention of 25 intronic bp), 2 further splice variants (positions +1 and +3) and a missense one (S81L).

Nonsense mediated decay was the case for the product of the synonymous/splice variant as well as for a stopgain one.

As noted by the authors, individuals homozygous for the S81L variant had a less severe phenotype - among others - with mild degree of intellectual disability.

Functional studies included knockout of gnb5 in zebrafish, which was able to reproduce the human neurological, cardiac and ophthalmological phenotypes.

Alternative causes for these phenotypes (incl. chromosomal or metabolic disorders) were ruled out.

Affected individuals might benefit interventions for their heart rate disturbance as appears to be the case in the article as well as subsequent studies.

PMID: 27677260 describes an extended consanguineous Saudi family with 5 individuals homozygous for the S81L variant. Common features included severe language delay, ADHD, but normal cognition in those available for evaluation. Seizures were not reported. Pathogenicity of the S81L variant is further supported by functional studies.

PMID: 28697420 describes in detail 2 individuals from a large consanguineous pedigree confirmed to be homozygous for a single nucleotide deletion in GNB5. The phenotype included severe DD/ID, seizures, sinus bradycardia with frequent sinus pauses and ophthalmological problems. Sinus arrhythmia and or seizures were documented in several other relatives deceased and unavailable for testing.

PMID: 28327206 reports on 2 subjects previously included in PMID: 27523599.

PMID: 29368331 describes a child with severe developmental delay, nystagmus and sinus arrhythmia necessitating a pacemaker. EEG was abnormal although no frank seizures were observed. The child was compound heterozygous for a novel missense variant (R246Q) as well a 5 basepair deletion.

GNB5 is included in diagnostic gene panels for intellectual disability offered by different laboratories.

As a result this gene can be considered for inclusion in this panel as green.
Sources: Literature, Expert Review
Short QT syndrome v0.19 PKP2 Sarah Leigh Publications for gene: PKP2 were set to
Short QT syndrome v0.18 SCN10A Sarah Leigh Publications for gene: SCN10A were set to PMID:30177317
Short QT syndrome v0.17 SLC4A3 Sarah Leigh Marked gene: SLC4A3 as ready
Short QT syndrome v0.17 SLC4A3 Sarah Leigh Added comment: Comment when marking as ready: Not associated with phenotype in OMIM or in Gen2Phen. One variant was identified in two unrelated families. The variant segregates with short QT in both families and an Slc4a3 knockdown in zebrafish causes increased cardiac pHi, short QTc, and reduced systolic duration, which was rescued by wildtype SLC4A3, but not by the variant (PMID: 29167417).
Short QT syndrome v0.17 SLC4A3 Sarah Leigh Gene: slc4a3 has been classified as Green List (High Evidence).
Intellectual disability v2.537 ATP6V1A Louise Daugherty Phenotypes for gene: ATP6V1A were changed from # 618012 EPILEPTIC ENCEPHALOPATHY, INFANTILE OR EARLY CHILDHOOD, 3; IECEE3 to Epileptic encephalopathy, infantile or early childhood, 3 618012; Cutis laxa, autosomal recessive, type IID 617403
Intellectual disability v2.536 ATP6V1A Louise Daugherty commented on gene: ATP6V1A
Intellectual disability v2.536 ATP1A1 Louise Daugherty Classified gene: ATP1A1 as Green List (high evidence)
Intellectual disability v2.536 ATP1A1 Louise Daugherty Added comment: Comment on list classification: New gene added by external expert and reviewed by curation team, enough evidence to support gene-disease association and relevance to this panel to rate this gene Green
Intellectual disability v2.536 ATP1A1 Louise Daugherty Gene: atp1a1 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.927 ISPD Ivone Leong Mode of inheritance for gene: ISPD was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.926 ISPD Ivone Leong Phenotypes for gene: ISPD were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7, 614643
Intellectual disability v2.535 ATP1A1 Louise Daugherty commented on gene: ATP1A1
Genetic epilepsy syndromes v0.925 IKBKG Ivone Leong Marked gene: IKBKG as ready
Genetic epilepsy syndromes v0.925 IKBKG Ivone Leong Gene: ikbkg has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.925 IKBKG Ivone Leong Publications for gene: IKBKG were set to
Short QT syndrome v0.17 SLC22A5 Sarah Leigh Phenotypes for gene: SLC22A5 were changed from arrhythmia; short QT; cardiomyopathy; primary carnitine deficiency to arrhythmia; short QT; cardiomyopathy; primary carnitine deficiency; Carnitine deficiency, systemic primary 212140
Genetic epilepsy syndromes v0.924 IKBKG Ivone Leong Classified gene: IKBKG as Green List (high evidence)
Genetic epilepsy syndromes v0.924 IKBKG Ivone Leong Added comment: Comment on list classification: Promoted from amber to green. Incontinentia pigmenti is confirmed by OMIM and Gene2Phenotype. There are >3 unrelated families with a variant in this gene diagnosed with incontinentia pigmenti who have seizures (PMID: 30151858,28794079,24339369). Neurological symptoms (including seizures) are affect ~30% of patients with incontinentia pigmenti (PMID:28870493).
Genetic epilepsy syndromes v0.924 IKBKG Ivone Leong Gene: ikbkg has been classified as Green List (High Evidence).
Short QT syndrome v0.16 SLC22A5 Sarah Leigh Publications for gene: SLC22A5 were set to PMID: 7254270; 7131143; 26190315; 29198778
Short QT syndrome v0.15 SCN5A Sarah Leigh Marked gene: SCN5A as ready
Short QT syndrome v0.15 SCN5A Sarah Leigh Gene: scn5a has been classified as Amber List (Moderate Evidence).
Short QT syndrome v0.15 SCN5A Sarah Leigh Tag watchlist tag was added to gene: SCN5A.
Short QT syndrome v0.15 SCN5A Sarah Leigh Classified gene: SCN5A as Amber List (moderate evidence)
Short QT syndrome v0.15 SCN5A Sarah Leigh Gene: scn5a has been classified as Amber List (Moderate Evidence).
Short QT syndrome v0.14 SCN5A Sarah Leigh Publications for gene: SCN5A were set to PMID: 22490985; 29697308
Short QT syndrome v0.13 SCN5A Sarah Leigh Phenotypes for gene: SCN5A were changed from short qt; Brugada; family history of sudden death to Brugada syndrome 1 601144
Short QT syndrome v0.12 LRP5 Sarah Leigh Publications for gene: LRP5 were set to PMID: 30309679
Short QT syndrome v0.11 LRP5 Sarah Leigh Classified gene: LRP5 as Red List (low evidence)
Short QT syndrome v0.11 LRP5 Sarah Leigh Gene: lrp5 has been classified as Red List (Low Evidence).
Genetic epilepsy syndromes v0.923 EIF3F Sarah Leigh Marked gene: EIF3F as ready
Genetic epilepsy syndromes v0.923 EIF3F Sarah Leigh Added comment: Comment when marking as ready: Not associated with phenotype in OMIM or in Gen2Phen. A single variant (rs141976414, ENSP00000310040.4:p.Phe232Val) has been identified as a homozygote in 9 subjects with intellectual disability and other phenotypic features, 6/9 have seizures. rs141976414 has a frequency of 0.12% in non-Finnish Europeans, however, it is not found as a homozygote in gnomAD (http://gnomad.broadinstitute.org). Supportive functional studies were also provided (PMID 30409806).
Genetic epilepsy syndromes v0.923 EIF3F Sarah Leigh Gene: eif3f has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.923 EIF3F Sarah Leigh Classified gene: EIF3F as Green List (high evidence)
Genetic epilepsy syndromes v0.923 EIF3F Sarah Leigh Gene: eif3f has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.922 EIF3F Sarah Leigh Classified gene: EIF3F as Green List (high evidence)
Genetic epilepsy syndromes v0.922 EIF3F Sarah Leigh Gene: eif3f has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.921 IKBKG Ivone Leong Mode of inheritance for gene: IKBKG was changed from to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Genetic epilepsy syndromes v0.920 RHOBTB2 Sarah Leigh Marked gene: RHOBTB2 as ready
Genetic epilepsy syndromes v0.920 RHOBTB2 Sarah Leigh Added comment: Comment when marking as ready: Associated with phenotype in OMIM and not in Gen2Phen. At least 6 variants identified in 8 unrelated cases. In vitro functional studies suggest that pathogenicity results from increased expression or reduced degradation of the variant peptides in affected individuals (PMID 29276004).
Genetic epilepsy syndromes v0.920 RHOBTB2 Sarah Leigh Gene: rhobtb2 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.920 RHOBTB2 Sarah Leigh Classified gene: RHOBTB2 as Green List (high evidence)
Genetic epilepsy syndromes v0.920 RHOBTB2 Sarah Leigh Gene: rhobtb2 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.919 RHOBTB2 Sarah Leigh Phenotypes for gene: RHOBTB2 were changed from Global developmental delay; Intellectual disability; Seizures; Postnatal microcephaly to Epileptic encephalopathy, early infantile, 64 618004
Genetic epilepsy syndromes v0.918 FUT8 Sarah Leigh Marked gene: FUT8 as ready
Genetic epilepsy syndromes v0.918 FUT8 Sarah Leigh Added comment: Comment when marking as ready: Associated with phenotype in OMIM and not in Gen2Phen. At least 4 variants identified in 3 unrelated cases, supportive segregation and in vitro data was also presented.
Genetic epilepsy syndromes v0.918 FUT8 Sarah Leigh Gene: fut8 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.918 FUT8 Sarah Leigh Classified gene: FUT8 as Green List (high evidence)
Genetic epilepsy syndromes v0.918 FUT8 Sarah Leigh Gene: fut8 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.917 ATP6V1A Sarah Leigh Marked gene: ATP6V1A as ready
Genetic epilepsy syndromes v0.917 ATP6V1A Sarah Leigh Added comment: Comment when marking as ready: Associated with phenotype in OMIM and not in Gen2Phen. At least 4 variants were identified in unrelated cases of Epileptic encephalopathy, infantile or early childhood, 3 618012, one variant (c.1045G>A, NM_001690.3, p.D349N) appear give gain of function results in in vitro analysis, whereas the others had loss of function. Two homozygous variants were reported in two unrelated cases of Cutis laxa, autosomal recessive, type IID 617403 who both had seizures as part of their phenotypes.
Genetic epilepsy syndromes v0.917 ATP6V1A Sarah Leigh Gene: atp6v1a has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.917 ATP6V1A Sarah Leigh Added comment: Comment on phenotypes: Monoallelic variants associated with Epileptic encephalopathy, infantile or early childhood, 3 618012 and biallelic variants associated with Cutis laxa, autosomal recessive, type IID 617403. Both phenotypes include seizures.
Genetic epilepsy syndromes v0.917 ATP6V1A Sarah Leigh Phenotypes for gene: ATP6V1A were changed from # 618012 EPILEPTIC ENCEPHALOPATHY, INFANTILE OR EARLY CHILDHOOD, 3 - IECEE3; # 617403 CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IID - ARCL2D to Epileptic encephalopathy, infantile or early childhood, 3 618012; Cutis laxa, autosomal recessive, type IID 617403
Genetic epilepsy syndromes v0.916 ATP6V1A Sarah Leigh Classified gene: ATP6V1A as Green List (high evidence)
Genetic epilepsy syndromes v0.916 ATP6V1A Sarah Leigh Gene: atp6v1a has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.915 ATP1A1 Sarah Leigh Marked gene: ATP1A1 as ready
Genetic epilepsy syndromes v0.915 ATP1A1 Sarah Leigh Added comment: Comment when marking as ready: Not associated with phenotype in OMIM or in Gen2Phen. Three heterozygous de novo variants reported in three unrelated cases manifesting with refractory seizures, severe hypomagnesemia and severe intellectual disability. Supportive in vitro studies were also presented.
Genetic epilepsy syndromes v0.915 ATP1A1 Sarah Leigh Gene: atp1a1 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.915 ATP1A1 Sarah Leigh Classified gene: ATP1A1 as Green List (high evidence)
Genetic epilepsy syndromes v0.915 ATP1A1 Sarah Leigh Gene: atp1a1 has been classified as Green List (High Evidence).
Intellectual disability v2.535 KDM5B Konstantinos Varvagiannis reviewed gene: KDM5B: Rating: GREEN; Mode of pathogenicity: None; Publications: 29276005, 30409806; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.914 EIF3F Konstantinos Varvagiannis gene: EIF3F was added
gene: EIF3F was added to Genetic epilepsy syndromes. Sources: Literature,Expert Review
Mode of inheritance for gene: EIF3F was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EIF3F were set to 30409806
Phenotypes for gene: EIF3F were set to Intellectual disability; Seizures; Behavioral abnormality; Sensorineural hearing impairment
Penetrance for gene: EIF3F were set to Complete
Review for gene: EIF3F was set to GREEN
Added comment: EIF3F was identified in a recent DDD publication (PMID: 30409806) as a cause of autosomal recessive intellectual disability.

All 9 individuals reported were homozygous for a missense variant (Phe232Val - rs141976414) which has a frequency of 0.12% in non-Finnish Europeans.

Features included intellectual disability (9/9), seizures (6/9), behavioral problems (3/9) and sensorineural hearing loss (3/9). Facial features were not specific.

Extensive functional studies were performed and support pathogenicity of the variant in the homozygous state (reduced protein levels, reduced translation rate in line with the role of EIF3F encoding a subunit for eukaryotic translation initiation factor 3, as well as reduced proliferation rates).

As a result this gene can be considered for inclusion in this panel as green (or amber).
Sources: Literature, Expert Review
Intellectual disability v2.535 EIF3F Konstantinos Varvagiannis gene: EIF3F was added
gene: EIF3F was added to Intellectual disability. Sources: Literature,Expert Review
Mode of inheritance for gene: EIF3F was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EIF3F were set to 30409806
Phenotypes for gene: EIF3F were set to Intellectual disability; Seizures; Behavioral abnormality; Sensorineural hearing impairment
Penetrance for gene: EIF3F were set to Complete
Review for gene: EIF3F was set to GREEN
Added comment: EIF3F was identified in a recent DDD publication (PMID: 30409806) as a cause of autosomal recessive intellectual disability.

All 9 individuals reported were homozygous for a missense variant (Phe232Val - rs141976414) which has a frequency of 0.12% in non-Finnish Europeans.

Features included intellectual disability (9/9), seizures (6/9), behavioral problems (3/9) and sensorineural hearing loss (3/9). Facial features were not specific.

Extensive functional studies were performed and support pathogenicity of the variant in the homozygous state (reduced protein levels, reduced translation rate in line with the role of EIF3F encoding a subunit for eukaryotic translation initiation factor 3, as well as reduced proliferation rates).

As a result this gene can be considered for inclusion in this panel as green.
Sources: Literature, Expert Review
Congenital disorders of glycosylation v1.19 FUT8 Konstantinos Varvagiannis gene: FUT8 was added
gene: FUT8 was added to Congenital disorders of glycosylation. Sources: Literature
Mode of inheritance for gene: FUT8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FUT8 were set to 29304374
Phenotypes for gene: FUT8 were set to Congenital disorder of glycosylation with defective fucosylation, 618005
Penetrance for gene: FUT8 were set to Complete
Review for gene: FUT8 was set to GREEN
Added comment: PMID: 29304374 reports on 3 unrelated individuals with biallelic pathogenic variants in FUT8.

Two of the patients were born to consanguineous parents and were found to be homozygous for stopgain variants (p.Arg239* in one family and p.Arg315* in the other). A third patient was compound heterozygous for a missense as well as a splice variant.

All three presented with similar phenotype consisting of polyhydramnios (2 out of 3), IUGR and failure to thrive with short stature (3/3), severe developmental delay (3/3) with microcephaly (3/3) and seizures (3/3). Variable respiratory problems were also noted in all.

Western blot demonstrated loss of FUT8 protein expression in one individual homozygous for a stopgain mutation as well as the patient who was compound heterozygous for the missense and the splice variant. The splice variant was further shown to produce a shorter transcript due to lack of exon 9, leading to an in-frame deletion of 59 residues critical for the protein function.

Additional studies confirmed the fucosylation defect compared to controls.

The authors note that while Fut8 knockout mice are born normal, 70% die within the first 3 days due to severe growth retardation and respiratory deficiency (similarly to what is observed in humans, though to a lesser extent).

This type of CDG is associated with a normal carbohydrate-deficient transferrin (CDT) pattern.

As a result this gene can be considered for inclusion in this panel probably as green.
Sources: Literature
Genetic epilepsy syndromes v0.914 FUT8 Konstantinos Varvagiannis gene: FUT8 was added
gene: FUT8 was added to Genetic epilepsy syndromes. Sources: Literature,Expert Review
Mode of inheritance for gene: FUT8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FUT8 were set to 29304374
Phenotypes for gene: FUT8 were set to Congenital disorder of glycosylation with defective fucosylation, 618005
Penetrance for gene: FUT8 were set to Complete
Review for gene: FUT8 was set to GREEN
Added comment: PMID: 29304374 reports on 3 unrelated individuals with biallelic pathogenic variants in FUT8.

Two of the patients were born to consanguineous parents and were found to be homozygous for stopgain variants (p.Arg239* in one family and p.Arg315* in the other). A third patient was compound heterozygous for a missense as well as a splice variant.

All three presented with similar phenotype consisting of polyhydramnios (2 out of 3), IUGR and failure to thrive with short stature (3/3), severe developmental delay (3/3) with microcephaly (3/3) and seizures (3/3). Variable respiratory problems were also noted in all.

Western blot demonstrated loss of FUT8 protein expression in one individual homozygous for a stopgain mutation as well as the patient who was compound heterozygous for the missense and the splice variant. The splice variant was further shown to produce a shorter transcript due to lack of exon 9, leading to an in-frame deletion of 59 residues critical for the protein function.

Additional studies confirmed the fucosylation defect compared to controls.

The authors note that while Fut8 knockout mice are born normal, 70% die within the first 3 days due to severe growth retardation and respiratory deficiency (similarly to what is observed in humans, though to a lesser extent).

As a result this gene can be considered for inclusion in this panel probably as green (3 unrelated families, strong additional functional data, consistent phenotype) or amber.
Sources: Literature, Expert Review
Intellectual disability v2.535 FUT8 Konstantinos Varvagiannis gene: FUT8 was added
gene: FUT8 was added to Intellectual disability. Sources: Literature,Expert Review
Mode of inheritance for gene: FUT8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FUT8 were set to 29304374
Phenotypes for gene: FUT8 were set to Congenital disorder of glycosylation with defective fucosylation, 618005
Penetrance for gene: FUT8 were set to Complete
Review for gene: FUT8 was set to GREEN
Added comment: PMID: 29304374 reports on 3 unrelated individuals with biallelic pathogenic variants in FUT8.

Two of the patients were born to consanguineous parents and were found to be homozygous for stopgain variants (p.Arg239* in one family and p.Arg315* in the other). A third patient was compound heterozygous for a missense as well as a splice variant.

All three presented with similar phenotype consisting of polyhydramnios (2 out of 3), IUGR and failure to thrive with short stature (3/3), severe developmental delay (3/3) with microcephaly (3/3) and seizures (3/3). Variable respiratory problems were also noted in all.

Western blot demonstrated loss of FUT8 protein expression in one individual homozygous for a stopgain mutation as well as the patient who was compound heterozygous for the missense and the splice variant. The splice variant was further shown to produce a shorter transcript due to lack of exon 9, leading to an in-frame deletion of 59 residues critical for the protein function.

Additional studies confirmed the fucosylation defect compared to controls.

The authors note that while Fut8 knockout mice are born normal, 70% die within the first 3 days due to severe growth retardation and respiratory deficiency (similarly to what is observed in humans, though to a lesser extent).

As a result this gene can be considered for inclusion in this panel probably as green (3 unrelated families, strong additional functional data, consistent phenotype) or amber.
Sources: Literature, Expert Review
Genetic epilepsy syndromes v0.914 ATP6V1A Konstantinos Varvagiannis gene: ATP6V1A was added
gene: ATP6V1A was added to Genetic epilepsy syndromes. Sources: Literature,Expert Review
Mode of inheritance for gene: ATP6V1A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ATP6V1A were set to 29668857; 28065471
Phenotypes for gene: ATP6V1A were set to # 618012 EPILEPTIC ENCEPHALOPATHY, INFANTILE OR EARLY CHILDHOOD, 3 - IECEE3; # 617403 CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IID - ARCL2D
Penetrance for gene: ATP6V1A were set to unknown
Review for gene: ATP6V1A was set to GREEN
Added comment: Heterozygous mutations in ATP6V1A cause Epileptic encephalopathy, infantile or early childhood, type 3 (MIM 618012).

PMID: 29668857 reports 4 individuals from 4 families with de novo pathogenic variants in ATP6V1A. The phenotype was consistent with a developmental encephalopathy with epilepsy.

All patients were found to harbor missense variants. The variants resulted in altered lysosomal homeostasis, abnormal neuritogenesis and synaptic density. However in one of the variants tested (p.Asp100Tyr) pathogenicity was mediated by loss-of-function mechanism while for another (p.Asp349Asn) by gain-of-function mechanism.

Differences in severity were noted, with two variants (incl. Asp100Tyr) being associated with a more severe phenotype and the two other (incl. Asp349Asn) with milder degrees of ID and epilepsy.

Biallelic ATP6V1A mutations cause Cutis laxa type IID (MIM 617403). PMID: 28065471 is the first report on 3 individuals from 3 different families (2 of which were consanguineous). All patients were homozygous for ATP6V1A pathogenic variants. All three presented with hypotonia, one (or possibly two) with developmental delay and two with seizures although the developmental phenotype is not further commented on. (Additional patients described in the article harbored mutations in other genes and were not considered).

As a result, this gene can be considered for inclusion in this panel as green.
Sources: Literature, Expert Review
Intellectual disability v2.535 ATP6V1A Konstantinos Varvagiannis gene: ATP6V1A was added
gene: ATP6V1A was added to Intellectual disability. Sources: Literature,Expert Review
Mode of inheritance for gene: ATP6V1A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ATP6V1A were set to 29668857; 28065471
Phenotypes for gene: ATP6V1A were set to # 618012 EPILEPTIC ENCEPHALOPATHY, INFANTILE OR EARLY CHILDHOOD, 3; IECEE3
Penetrance for gene: ATP6V1A were set to unknown
Review for gene: ATP6V1A was set to GREEN
Added comment: Heterozygous mutations in ATP6V1A cause Epileptic encephalopathy, infantile or early childhood, type 3 (MIM 618012).

PMID: 29668857 reports 4 individuals from 4 families with de novo pathogenic variants in ATP6V1A. The phenotype was consistent with a developmental encephalopathy with epilepsy.

All patients were found to harbor missense variants. The variants resulted in altered lysosomal homeostasis, abnormal neuritogenesis and synaptic density. However in one of the variants tested (p.Asp100Tyr) pathogenicity was mediated by loss-of-function mechanism while for another (p.Asp349Asn) by gain-of-function mechanism.

Differences in severity were noted, with two variants (incl. Asp100Tyr) being associated with a more severe phenotype and the two other (incl. Asp349Asn) with milder degrees of ID and epilepsy.

Biallelic ATP6V1A mutations cause Cutis laxa type IID (MIM 617403). PMID: 28065471 is the first report on 3 individuals from 3 different families (2 of which were consanguineous). All patients were homozygous for ATP6V1A pathogenic variants. All three presented with hypotonia, one (or possibly two) with developmental delay and two with seizures although the developmental phenotype is not further commented on. (Additional patients described in the article harbored mutations in other genes and were not considered).

As a result, this gene can be considered for inclusion in this panel as green (or amber).
Sources: Literature, Expert Review
Genetic epilepsy syndromes v0.914 ATP1A1 Konstantinos Varvagiannis gene: ATP1A1 was added
gene: ATP1A1 was added to Genetic epilepsy syndromes. Sources: Literature,Expert Review
Mode of inheritance for gene: ATP1A1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ATP1A1 were set to 30388404
Phenotypes for gene: ATP1A1 were set to Hypomagnesemia; Seizures; Intellectual disability
Penetrance for gene: ATP1A1 were set to unknown
Review for gene: ATP1A1 was set to GREEN
Added comment: PMID: 30388404 reports on 3 subjects from 3 families with de novo pathogenic variants in ATP1A1. All 3 presented with similar phenotype consisting of hypomagnesemia, early onset refractory seizures as well as intellectual disability.

Alternative causes of hypomagnesemia with seizures (eg. due to TRPM6 mutations) were excluded while the phenotype of the 3 patients differed from similar disorder in that hypomagnesemia as well as seizures were not responsive to magnesium supplementation.

Three different missense variants are reported (L302R, G303R, M859R) all as de novo occurences and after confirmation of paternity.

Functional studies were suggestive of loss of the ATPase function, abnormal cation permeabilities as well as reduced level of expression (the latter was significant for at least for 2 of the 3 variants).

Mutations in ATP1A1 have also been reported in patients with Charcot-Marie-Tooth type 2 (CMT2DD - MIM: 618036) although the variants reported to date map seem to cluster within the helical linker region (residues 592 to 608). The young age of the patients with epilepsy and intellectual disability did not allow conclusions on eventual peripheral neuropathy in these individuals.

As a result this gene can be considered for inclusion in this panel as green (or amber).
Sources: Literature, Expert Review
Intellectual disability v2.535 ATP1A1 Konstantinos Varvagiannis gene: ATP1A1 was added
gene: ATP1A1 was added to Intellectual disability. Sources: Expert Review,Literature
Mode of inheritance for gene: ATP1A1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ATP1A1 were set to 30388404
Phenotypes for gene: ATP1A1 were set to Hypomagnesemia; Seizures; Intellectual disability
Penetrance for gene: ATP1A1 were set to unknown
Review for gene: ATP1A1 was set to GREEN
Added comment: PMID: 30388404 reports on 3 subjects from 3 families with de novo pathogenic variants in ATP1A1. All 3 presented with similar phenotype consisting of hypomagnesemia, early onset refractory seizures as well as intellectual disability.

Alternative causes of hypomagnesemia with seizures (eg. due to TRPM6 mutations) were excluded while the phenotype of the 3 patients differed from similar disorder in that hypomagnesemia as well as seizures were not responsive to magnesium supplementation.

Three different missense variants are reported (L302R, G303R, M859R) all as de novo occurences and after confirmation of paternity.

Functional studies were suggestive of loss of the ATPase function, abnormal cation permeabilities as well as reduced level of expression (the latter was significant for at least for 2 of the 3 variants).

Mutations in ATP1A1 have also been reported in patients with Charcot-Marie-Tooth type 2 (CMT2DD - MIM: 618036) although the variants reported to date map seem to cluster within the helical linker region (residues 592 to 608). The young age of the patients with epilepsy and intellectual disability did not allow conclusions on eventual peripheral neuropathy in these individuals.

As a result this gene can be considered for inclusion in this panel as green (or amber).
Sources: Expert Review, Literature
Lipodystrophy - childhood onset v0.1 Ellen McDonagh Panel types changed to GMS Rare Disease Virtual
Genetic epilepsy syndromes v0.914 GLUL Louise Daugherty Added comment: Comment on mode of inheritance: changed MOI from OMIM and publication PMID:16267323
Genetic epilepsy syndromes v0.914 GLUL Louise Daugherty Mode of inheritance for gene: GLUL was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.913 GLUL Louise Daugherty Added comment: Comment on phenotypes: Added phenotypes suggested from expert review that indicate relevance to inclusion on the Genetic Epilepsy Syndromes panel
Genetic epilepsy syndromes v0.913 GLUL Louise Daugherty Phenotypes for gene: GLUL were changed from to Glutamine deficiency, congenital, 610015; seizures
Genetic epilepsy syndromes v0.912 GM2A Louise Daugherty Marked gene: GM2A as ready
Genetic epilepsy syndromes v0.912 GM2A Louise Daugherty Gene: gm2a has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.912 GM2A Louise Daugherty Classified gene: GM2A as Green List (high evidence)
Genetic epilepsy syndromes v0.912 GM2A Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green. Appropriate phenotypes, sufficient cases, and external review comment all support gene-disease association.
Genetic epilepsy syndromes v0.912 GM2A Louise Daugherty Gene: gm2a has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.911 GM2A Louise Daugherty Added comment: Comment on publications: Publications added support gene-disease association and rating of this gene to Green.
Genetic epilepsy syndromes v0.911 GM2A Louise Daugherty Publications for gene: GM2A were set to
Intellectual disability v2.535 GM2A Louise Daugherty Added comment: Comment on publications: added missing publications to support gene-disease association.
Intellectual disability v2.535 GM2A Louise Daugherty Publications for gene: GM2A were set to
Genetic epilepsy syndromes v0.910 GM2A Louise Daugherty Phenotypes for gene: GM2A were changed from GM2-gangliosidosis, AB variant, 272750; seizures to GM2-gangliosidosis, AB variant, 272750; seizures; Hexosaminidase activator deficiency; Tay-Sachs disease
Genetic epilepsy syndromes v0.909 GM2A Louise Daugherty Added comment: Comment on phenotypes: Added phenotypes suggested from expert review that indicate relevance to inclusion on the Genetic Epilepsy Syndromes panel
Genetic epilepsy syndromes v0.909 GM2A Louise Daugherty Phenotypes for gene: GM2A were changed from to GM2-gangliosidosis, AB variant, 272750; seizures
Genetic epilepsy syndromes v0.908 GM2A Louise Daugherty Mode of inheritance for gene: GM2A was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.907 GNB1 Louise Daugherty Marked gene: GNB1 as ready
Genetic epilepsy syndromes v0.907 GNB1 Louise Daugherty Gene: gnb1 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.907 GNB1 Louise Daugherty Classified gene: GNB1 as Green List (high evidence)
Genetic epilepsy syndromes v0.907 GNB1 Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green. Appropriate phenotype, sufficient cases (more than 20), and external review comment all support gene-disease association.
Genetic epilepsy syndromes v0.907 GNB1 Louise Daugherty Gene: gnb1 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.906 GNB1 Louise Daugherty Mode of inheritance for gene: GNB1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic epilepsy syndromes v0.905 GNB1 Louise Daugherty Publications for gene: GNB1 were set to 27108799; 25529582; 27108799
Genetic epilepsy syndromes v0.904 GNB1 Louise Daugherty Added comment: Comment on publications: 13 unrelated patients with autosomal dominant mental retardation-42 Petrovski et al. (2016) PMID:27108799 identified 9 different de novo heterozygous missense mutations in the GNB1 gene, the variants were confirmed by Sanger sequencing.
Genetic epilepsy syndromes v0.904 GNB1 Louise Daugherty Publications for gene: GNB1 were set to
Genetic epilepsy syndromes v0.903 GNB1 Louise Daugherty Added comment: Comment on phenotypes: correction of the MIMid
Genetic epilepsy syndromes v0.903 GNB1 Louise Daugherty Phenotypes for gene: GNB1 were changed from Mental retardation, autosomal dominant 42, 614018; seizures to Mental retardation, autosomal dominant 42, 616973; seizures
Genetic epilepsy syndromes v0.902 GNB1 Louise Daugherty Added comment: Comment on phenotypes: Added phenotypes suggested from expert review that indicate relevance to inclusion on the Genetic Epilepsy Syndromes panel
Genetic epilepsy syndromes v0.902 GNB1 Louise Daugherty Phenotypes for gene: GNB1 were changed from to Mental retardation, autosomal dominant 42, 614018; seizures
Genetic epilepsy syndromes v0.901 GOSR2 Louise Daugherty Marked gene: GOSR2 as ready
Genetic epilepsy syndromes v0.901 GOSR2 Louise Daugherty Gene: gosr2 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.901 GOSR2 Louise Daugherty commented on gene: GOSR2: added founder-effect tag. Even though there is a founder effect in this population, there is further evidence for it being the gene of interest by the fact that there is more than one variant identified so supports a green rating on the current evidence.
Genetic epilepsy syndromes v0.901 GOSR2 Louise Daugherty Tag founder-effect tag was added to gene: GOSR2.
Genetic epilepsy syndromes v0.901 GOSR2 Louise Daugherty Classified gene: GOSR2 as Green List (high evidence)
Genetic epilepsy syndromes v0.901 GOSR2 Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green. Appropriate phenotype, sufficient cases, and external review comment all support gene-disease association.
Genetic epilepsy syndromes v0.901 GOSR2 Louise Daugherty Gene: gosr2 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.900 GOSR2 Louise Daugherty edited their review of gene: GOSR2: Added comment: External review notes that there are Corbett et al., 2011 (PMID: 21549339) reported five unrelated individuals reported with bi-allelic variants and denoted a founder effect.
To date, 17 reported patients with GOSR2‐mediated Progressive myoclonic epilepsy have been shown to carry the same homozygous c.430G>T (p.G144W) mutation, the result of a founder effect 21549339, 23449775, 24458321. However, Praschberger et al., (2015) PMID: 30363482 described a 61‐year‐old female patient suffering from progressive myoclonus epilepsy and was found to be compound heterozygous for the known c.430G>T and a novel c.491_493delAGA (p.K164del) GOSR2 mutation.; Changed rating: GREEN
Genetic epilepsy syndromes v0.900 GOSR2 Louise Daugherty Publications for gene: GOSR2 were set to 21549339; 30363482; 24458321; 27618868
Limb girdle muscular dystrophy v1.12 Ellen McDonagh List of related panels changed from to
Panel types changed to Rare Disease 100K; GMS Rare Disease
Congenital myopathy v1.61 Ellen McDonagh List of related panels changed from to
Panel types changed to Rare Disease 100K; GMS Rare Disease
Congenital myaesthenic syndrome v1.10 Ellen McDonagh Panel name changed from Congenital myaesthenia to Congenital myaesthenic syndrome
List of related panels changed from Congenital myasthenia to Congenital myaesthenia; Congenital myasthenia
Panel types changed to Rare Disease 100K; GMS Rare Disease
Congenital muscular dystrophy v1.16 Ellen McDonagh List of related panels changed from to
Panel types changed to Rare Disease 100K; GMS Rare Disease
Genetic epilepsy syndromes v0.899 GOSR2 Louise Daugherty Publications for gene: GOSR2 were set to 21549339; 30363482; 24458321
Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome v1.6 Ellen McDonagh Panel name changed from Cockayne and Xeroderma Pigmentosum-like disorders to Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome
List of related panels changed from Cockayne syndrome; Xeroderma Pigmentosum-like disorders; XP-like disorders to Cockayne and Xeroderma Pigmentosum-like disorders; Cockayne syndrome; Xeroderma Pigmentosum-like disorders; XP-like disorders
Panel types changed to Rare Disease 100K; GMS Rare Disease
Pneumothorax - familial v1.7 Ellen McDonagh Panel name changed from Familial Pneumothorax to Pneumothorax - familial
List of related panels changed from Familial Primary Spontaneous Pneumothorax to Familial Pneumothorax; Familial Primary Spontaneous Pneumothorax
Panel types changed to Rare Disease 100K; GMS Rare Disease
Pulmonary arterial hypertension v1.37 Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease
Hereditary haemorrhagic telangiectasia v1.30 Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease
Nephrocalcinosis or nephrolithiasis v1.15 Ellen McDonagh Panel name changed from Renal tract calcification (or Nephrolithiasis/nephrocalcinosis) to Nephrocalcinosis or nephrolithiasis
List of related panels changed from Renal tract calcification (or Nephrolithiasis or nephrocalcinosis) to Renal tract calcification (or Nephrolithiasis or nephrocalcinosis); Renal tract calcification (or Nephrolithiasis/nephrocalcinosis)
Panel types changed to Rare Disease 100K; GMS Rare Disease
Atypical haemolytic uraemic syndrome v1.4 Ellen McDonagh List of related panels changed from to
Panel types changed to Rare Disease 100K; GMS Rare Disease
Renal tubulopathies v1.9 Ellen McDonagh Panel name changed from Renal tubular acidosis to Renal tubulopathies
List of related panels changed from to Renal tubular acidosis
Panel types changed to Rare Disease 100K; GMS Rare Disease
Membranoproliferative glomerulonephritis v1.2 Ellen McDonagh Panel name changed from Primary Membranoproliferative Glomerulonephritis to Membranoproliferative glomerulonephritis
List of related panels changed from PMG; MPGN to PMG; MPGN; Primary Membranoproliferative Glomerulonephritis
Panel types changed to Rare Disease 100K; GMS Rare Disease
Proteinuric renal disease v1.12 Ellen McDonagh List of related panels changed from to
Panel types changed to Rare Disease 100K; GMS Rare Disease
Haematuria v1.15 Ellen McDonagh Panel name changed from Familial haematuria to Haematuria
List of related panels changed from Alport syndrome to Alport syndrome; Familial haematuria
Panel types changed to Rare Disease 100K; GMS Rare Disease
Leukodystrophy - adult onset v1.23 Ellen McDonagh Panel name changed from Inherited white matter disorders to Leukodystrophy - adult onset
List of related panels changed from to Inherited white matter disorders
Panel types changed to Rare Disease 100K; GMS Rare Disease
Osteogenesis imperfecta v1.13 Ellen McDonagh Panel name changed from Osteogenesis Imperfecta to Osteogenesis imperfecta
List of related panels changed from Osteogenesis imperfecta to Osteogenesis Imperfecta
Panel types changed to Rare Disease 100K; GMS Rare Disease
Amelogenesis imperfecta v1.6 Ellen McDonagh Panel name changed from Amelogenesis Imperfecta to Amelogenesis imperfecta
List of related panels changed from to Amelogenesis Imperfecta
Panel types changed to Rare Disease 100K; GMS Rare Disease
Familial rhabdoid tumours v1.1 Ellen McDonagh Panel name changed from Familial rhabdomyosarcoma to Familial rhabdoid tumours
List of related panels changed from Familial rhabdomyosarcoma or sarcoma to Familial rhabdomyosarcoma; Familial rhabdomyosarcoma or sarcoma
Panel types changed to Rare Disease 100K; GMS Rare Disease
Pancreatitis v0.21 Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease
Polycystic liver disease v0.35 Ellen McDonagh Panel name changed from Ductal plate malformation (DPM) to Polycystic liver disease
List of related panels changed from to Ductal plate malformation (DPM)
Panel types changed to Rare Disease 100K; GMS Rare Disease
Stickler syndrome v1.24 Ellen McDonagh List of related panels changed from to
Panel types changed to Rare Disease 100K; GMS Rare Disease
Corneal dystrophy v1.5 Ellen McDonagh Panel name changed from Corneal abnormalities to Corneal dystrophy
List of related panels changed from to Corneal abnormalities
Panel types changed to Rare Disease 100K; GMS Rare Disease
Optic neuropathy v1.24 Ellen McDonagh Panel name changed from Inherited optic neuropathies to Optic neuropathy
List of related panels changed from to Inherited optic neuropathies
Optic neuropathy v1.23 Ellen McDonagh List of related panels changed from to
Panel types changed to Rare Disease 100K; GMS Rare Disease
Arrythmogenic cardiomyopathy v1.6 Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease
Arrythmogenic cardiomyopathy v1.5 Ellen McDonagh Panel name changed from Arrhythmogenic Right Ventricular Cardiomyopathy to Arrythmogenic cardiomyopathy
List of related panels changed from to Arrhythmogenic Right Ventricular Cardiomyopathy
Dilated cardiomyopathy - teen and adult v1.35 Ellen McDonagh Panel name changed from Dilated Cardiomyopathy and conduction defects to Dilated cardiomyopathy - teen and adult
List of related panels changed from Dilated Cardiomyopathy; Dilated Cardiomyopathy (DCM) to Dilated Cardiomyopathy and conduction defects; Dilated Cardiomyopathy; Dilated Cardiomyopathy (DCM)
Panel types changed to Rare Disease 100K; GMS Rare Disease
Hypertrophic cardiomyopathy - teen and adult v1.22 Ellen McDonagh Panel name changed from Hypertrophic Cardiomyopathy to Hypertrophic cardiomyopathy - teen and adult
List of related panels changed from HCM to Hypertrophic Cardiomyopathy; HCM
Panel types changed to Rare Disease 100K; GMS Rare Disease
Short QT syndrome v0.10 Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease
Catecholaminergic polymorphic VT v1.3 Ellen McDonagh Panel name changed from Catecholaminergic Polymorphic Ventricular Tachycardia to Catecholaminergic polymorphic VT
List of related panels changed from to Catecholaminergic Polymorphic Ventricular Tachycardia
Panel types changed to Rare Disease 100K; GMS Rare Disease
Brugada syndrome v1.11 Ellen McDonagh List of related panels changed from to
Panel types changed to Rare Disease 100K; GMS Rare Disease
Long QT syndrome v1.7 Ellen McDonagh List of related panels changed from to Long QT
Long QT syndrome v1.6 Ellen McDonagh List of related panels changed from to
Panel types changed to Rare Disease 100K; GMS Rare Disease
Inherited colorectal cancer (with or without polyposis) v1.7 Ellen McDonagh Panel name changed from GI tract tumours to Inherited colorectal cancer (with or without polyposis)
List of related panels changed from Familial colon cancer; Multiple bowel polyps; Peutz-Jeghers syndrome; GI tract to GI tract tumours; Familial colon cancer; Multiple bowel polyps; Peutz-Jeghers syndrome; GI tract
Panel types changed to Rare Disease 100K; GMS Rare Disease
Inherited ovarian cancer (without breast cancer) v1.2 Ellen McDonagh Panel name changed from Familial ovarian cancer to Inherited ovarian cancer (without breast cancer)
List of related panels changed from to Familial ovarian cancer
Panel types changed to Rare Disease 100K; GMS Rare Disease
Hereditary spastic paraplegia - adult onset v0.0 Ellen McDonagh Added Panel Hereditary spastic paraplegia - adult onset
Set panel types to: GMS Rare Disease
Hereditary spastic paraplegia v1.70 Ellen McDonagh Panel name changed from Hereditary spastic paraplegia to Hereditary spastic paraplegia - childhood onset
Hereditary spastic paraplegia v1.69 Ellen McDonagh List of related panels changed from to Hereditary spastic paraplegia
Primary pigmented nodular adrenocortical disease v0.0 Ellen McDonagh Added Panel Primary pigmented nodular adrenocortical disease
Set panel types to: GMS Rare Disease
Rare genetic inflammatory skin disorders v0.0 Ellen McDonagh Added Panel Rare genetic inflammatory skin disorders
Set panel types to: GMS Rare Disease
Mosaic skin disorders - deep sequencing v0.0 Ellen McDonagh Added Panel Mosaic skin disorders - deep sequencing
Set panel types to: GMS Rare Disease
Vascular skin disorders v0.0 Ellen McDonagh Added Panel Vascular skin disorders
Set panel types to: GMS Rare Disease
Epidermodysplasia verruciformis v0.0 Ellen McDonagh Added Panel Epidermodysplasia verruciformis
Set panel types to: GMS Rare Disease
Neonatal erythroderma v0.0 Ellen McDonagh Added Panel Neonatal erythroderma
Set panel types to: GMS Rare Disease
Cutaneous photosensitivity with a likely genetic cause v0.0 Ellen McDonagh Added Panel Cutaneous photosensitivity with a likely genetic cause
Set panel types to: GMS Rare Disease
Pigmentary skin disorders v0.0 Ellen McDonagh Added Panel Pigmentary skin disorders
Set panel types to: GMS Rare Disease
Multiple monogenic benign skin tumours v0.0 Ellen McDonagh Added Panel Multiple monogenic benign skin tumours
Set panel types to: GMS Rare Disease
Autosomal recessive primary hypertrophic osteoarthropathy v0.0 Ellen McDonagh Added Panel Autosomal recessive primary hypertrophic osteoarthropathy
Set panel types to: GMS Rare Disease
Palmoplantar keratodermas v0.0 Ellen McDonagh Added Panel Palmoplantar keratodermas
Set panel types to: GMS Rare Disease
Ichthyosis and erythrokeratoderma v0.0 Ellen McDonagh Added Panel Ichthyosis and erythrokeratoderma
Set panel types to: GMS Rare Disease
Epidermolysis bullosa and congenital skin fragility v0.0 Ellen McDonagh Added Panel Epidermolysis bullosa and congenital skin fragility
Set panel types to: GMS Rare Disease
Ectodermal dysplasia v0.0 Ellen McDonagh Added Panel Ectodermal dysplasia
Set panel types to: GMS Rare Disease
Familial tumoral calcinosis v0.0 Ellen McDonagh Added Panel Familial tumoral calcinosis
Set panel types to: GMS Rare Disease
Surfactant deficiency v0.0 Ellen McDonagh Added Panel Surfactant deficiency
Set panel types to: GMS Rare Disease
Respiratory ciliopathies including non-CF bronchiectasis v0.0 Ellen McDonagh Added Panel Respiratory ciliopathies including non-CF bronchiectasis
Set panel types to: GMS Rare Disease
Hereditary ataxia v1.125 GOSR2 Louise Daugherty Phenotypes for gene: GOSR2 were changed from Ramsay Hunt syndrome; Epilepsy, progressive myoclonic 6, 614018 to Epilepsy, progressive myoclonic 6, 614018
Laterality disorders and isomerism v0.0 Ellen McDonagh Added Panel Laterality disorders and isomerism
Set panel types to: GMS Rare Disease
Tubulointerstitial kidney disease v0.0 Ellen McDonagh Added Panel Tubulointerstitial kidney disease
Set panel types to: GMS Rare Disease
Hereditary ataxia v1.124 GOSR2 Louise Daugherty Added comment: Comment on publications: Publications added support gene-disease association and rating of this gene to Green. Variants of GOSR2 are classified as causing less common Autosomal Recessive Hereditary Ataxias (i.e. reported in 1-5 families)
Hereditary ataxia v1.124 GOSR2 Louise Daugherty Publications for gene: GOSR2 were set to
Neuromuscular arthrogryposis v0.0 Ellen McDonagh Added Panel Neuromuscular arthrogryposis
Set panel types to: GMS Rare Disease
Hereditary ataxia v1.123 GOSR2 Louise Daugherty Added comment: Comment on phenotypes: Added missing phenotype
Hereditary ataxia v1.123 GOSR2 Louise Daugherty Phenotypes for gene: GOSR2 were changed from to Ramsay Hunt syndrome; Epilepsy, progressive myoclonic 6, 614018
Lipodystrophy - childhood onset v0.0 Ellen McDonagh Added Panel Lipodystrophy - childhood onset
Set panel types to: GMS Rare Disease
Genetic epilepsy syndromes v0.898 GOSR2 Louise Daugherty Added comment: Comment on publications: Added publications suggested from external expert review and additional publications to support upgrading of the gene to Green
Genetic epilepsy syndromes v0.898 GOSR2 Louise Daugherty Publications for gene: GOSR2 were set to
Primary lymphoedema v1.32 Ellen McDonagh Panel name changed from Lymphatic Disorders to Primary lymphoedema
List of related panels changed from Meiges disease;Meige disease;Milroy disease;Lymphoedema distichiasis;Lipoedema disease;Primary lymphoedema to Lymphatic Disorders; Meiges disease; Meige disease; Milroy disease; Lymphoedema distichiasis; Lipoedema disease
Bleeding and platelet disorders v0.0 Ellen McDonagh Added Panel Bleeding and platelet disorders
Set panel types to: GMS Rare Disease
Inherited bleeding disorders v1.146 Ellen McDonagh List of related panels changed from Inherited platelet disorders; Monogenic thrombophilia; Bleeding and platelet disorders; Inherited bleeding and or platelet disorders; Unprovoked Thrombosis before 40; Monogenic venous thrombosis to Inherited platelet disorders; Monogenic thrombophilia; Inherited bleeding and or platelet disorders; Unprovoked Thrombosis before 40; Monogenic venous thrombosis
Cholestasis v0.0 Ellen McDonagh Added Panel Cholestasis
Set panel types to: GMS Rare Disease
Neonatal cholestasis v1.3 Ellen McDonagh List of related panels changed from Cholestasis to
Hypophosphataemia or rickets v0.2 FGFR1 Ivone Leong Mode of inheritance for gene: FGFR1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hypophosphataemia or rickets v0.1 FGFR1 Ivone Leong gene: FGFR1 was added
gene: FGFR1 was added to Hypophosphataemia or rickets. Sources: Literature,Emory Genetics Laboratory
Mode of inheritance for gene: FGFR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: FGFR1 were set to Osteoglophonic dysplasia (166250); Hypophosphatemia
Hypophosphataemia or rickets v0.1 FAM20C Ivone Leong gene: FAM20C was added
gene: FAM20C was added to Hypophosphataemia or rickets. Sources: Literature,Expert list,Emory Genetics Laboratory
Mode of inheritance for gene: FAM20C was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FAM20C were set to Raine syndrome (259775)
Hypophosphataemia or rickets v0.1 SLC34A1 Ivone Leong gene: SLC34A1 was added
gene: SLC34A1 was added to Hypophosphataemia or rickets. Sources: Literature
Mode of inheritance for gene: SLC34A1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: SLC34A1 were set to Nephrolithiasis/osteoporosis, hypophosphatemic, 1 (612286)
Hypophosphataemia or rickets v0.1 CYP2R1 Ivone Leong gene: CYP2R1 was added
gene: CYP2R1 was added to Hypophosphataemia or rickets. Sources: Radboud University Medical Center, Nijmegen
Mode of inheritance for gene: CYP2R1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CYP2R1 were set to Rickets due to defect in vitamin D 25-hydroxylation (600081)
Hypophosphataemia or rickets v0.1 VDR Ivone Leong gene: VDR was added
gene: VDR was added to Hypophosphataemia or rickets. Sources: Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen
Mode of inheritance for gene: VDR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VDR were set to Rickets, vitamin D-resistant, type IIA (277440)
Hypophosphataemia or rickets v0.1 CYP27B1 Ivone Leong gene: CYP27B1 was added
gene: CYP27B1 was added to Hypophosphataemia or rickets. Sources: Expert list,Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen
Mode of inheritance for gene: CYP27B1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CYP27B1 were set to Vitamin D-dependent rickets, type I (264700)
Hypophosphataemia or rickets v0.1 ENPP1 Ivone Leong gene: ENPP1 was added
gene: ENPP1 was added to Hypophosphataemia or rickets. Sources: Expert list,UKGTN,Emory Genetics Laboratory,Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen
Mode of inheritance for gene: ENPP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ENPP1 were set to Hypophosphatemic rickets, autosomal recessive, 2 (613312)
Hypophosphataemia or rickets v0.1 CLCN5 Ivone Leong gene: CLCN5 was added
gene: CLCN5 was added to Hypophosphataemia or rickets. Sources: Expert list,Emory Genetics Laboratory
Mode of inheritance for gene: CLCN5 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: CLCN5 were set to Hypophosphatemic rickets (300554)
Hypophosphataemia or rickets v0.1 SLC9A3R1 Ivone Leong gene: SLC9A3R1 was added
gene: SLC9A3R1 was added to Hypophosphataemia or rickets. Sources: Radboud University Medical Center, Nijmegen
Mode of inheritance for gene: SLC9A3R1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: SLC9A3R1 were set to Nephrolithiasis/osteoporosis, hypophosphatemic, 2 (612287)
Hypophosphataemia or rickets v0.1 SLC34A3 Ivone Leong gene: SLC34A3 was added
gene: SLC34A3 was added to Hypophosphataemia or rickets. Sources: UKGTN,Emory Genetics Laboratory,Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen
Mode of inheritance for gene: SLC34A3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC34A3 were set to Hypophosphatemic rickets with hypercalciuria (241530)
Hypophosphataemia or rickets v0.1 DMP1 Ivone Leong gene: DMP1 was added
gene: DMP1 was added to Hypophosphataemia or rickets. Sources: UKGTN,Emory Genetics Laboratory,Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen
Mode of inheritance for gene: DMP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DMP1 were set to Hypophosphatemic rickets, AR (241520)
Hypophosphataemia or rickets v0.1 FGF23 Ivone Leong gene: FGF23 was added
gene: FGF23 was added to Hypophosphataemia or rickets. Sources: Expert list,UKGTN,Emory Genetics Laboratory,Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen
Mode of inheritance for gene: FGF23 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: FGF23 were set to Hypophosphatemic rickets, autosomal dominant (193100)
Hypophosphataemia or rickets v0.1 PHEX Ivone Leong gene: PHEX was added
gene: PHEX was added to Hypophosphataemia or rickets. Sources: Expert list,UKGTN,Emory Genetics Laboratory,Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen
Mode of inheritance for gene: PHEX was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: PHEX were set to Hypophosphatemic rickets, X-linked dominant (307800)
Bardet Biedl syndrome v0.0 Ellen McDonagh Added Panel Bardet Biedl syndrome
Set panel types to: GMS Rare Disease
Ehlers Danlos syndromes v1.35 Ellen McDonagh Panel name changed from Ehlers-Danlos syndromes to Ehlers Danlos syndromes
List of related panels changed from Classical Ehlers Danlos Syndrome; Ehlers-Danlos Syndrome (unusual phenotypes e.g. absent pain sense); Ehlers-Danlos syndrome type 3; Kyphoscoliotic Ehlers-Danlos syndrome; EDS to Classical Ehlers Danlos Syndrome; Ehlers-Danlos Syndrome (unusual phenotypes e.g. absent pain sense); Ehlers-Danlos syndrome type 3; Kyphoscoliotic Ehlers-Danlos syndrome; EDS; Ehlers-Danlos syndromes
Myotonia congenita v0.0 Ellen McDonagh Added Panel Myotonia congenita
Set panel types to: GMS Rare Disease
Paroxysmal neurological disorders, pain disorders and sleep disorders v0.0 Ellen McDonagh Added Panel Paroxysmal neurological disorders, pain disorders and sleep disorders
Set panel types to: GMS Rare Disease
Adult onset movement disorder v0.0 Ellen McDonagh Added Panel Adult onset movement disorder
Set panel types to: GMS Rare Disease
Possible mitochondrial disorder - nuclear genes v0.0 Ellen McDonagh Added Panel Possible mitochondrial disorder - nuclear genes
Set panel types to: GMS Rare Disease
Mitochondrial disorder with complex V deficiency v0.0 Ellen McDonagh Added Panel Mitochondrial disorder with complex V deficiency
Set panel types to: GMS Rare Disease
Mitochondrial disorder with complex IV deficiency v0.0 Ellen McDonagh Added Panel Mitochondrial disorder with complex IV deficiency
Set panel types to: GMS Rare Disease
Mitochondrial disorder with complex III deficiency v0.0 Ellen McDonagh Added Panel Mitochondrial disorder with complex III deficiency
Set panel types to: GMS Rare Disease
Mitochondrial disorder with complex II deficiency v0.0 Ellen McDonagh Added Panel Mitochondrial disorder with complex II deficiency
Set panel types to: GMS Rare Disease
Mitochondrial disorder with complex I deficiency v0.0 Ellen McDonagh Added Panel Mitochondrial disorder with complex I deficiency
Set panel types to: GMS Rare Disease
Mitochondrial DNA maintenance disorder v0.0 Ellen McDonagh Added Panel Mitochondrial DNA maintenance disorder
Set panel types to: GMS Rare Disease
Mitochondrial liver disease v0.0 Ellen McDonagh Added Panel Mitochondrial liver disease
Set panel types to: GMS Rare Disease
Pyruvate dehydrogenase (PDH) deficiency v0.0 Ellen McDonagh Added Panel Pyruvate dehydrogenase (PDH) deficiency
Set panel types to: GMS Rare Disease
Leber hereditary optic neuropathy v0.0 Ellen McDonagh Added Panel Leber hereditary optic neuropathy
Set panel types to: GMS Rare Disease
Lysosomal storage disorder v0.0 Ellen McDonagh Added Panel Lysosomal storage disorder
Set panel types to: GMS Rare Disease
Glycogen storage disease v0.0 Ellen McDonagh Added Panel Glycogen storage disease
Set panel types to: GMS Rare Disease
Lipoprotein lipase deficiency v0.0 Ellen McDonagh Added Panel Lipoprotein lipase deficiency
Set panel types to: GMS Rare Disease
Neuronal ceroid lipofuscinosis v0.0 Ellen McDonagh Added Panel Neuronal ceroid lipofuscinosis
Set panel types to: GMS Rare Disease
Inherited predisposition to acute myeloid leukaemia (AML) v0.0 Ellen McDonagh Added Panel Inherited predisposition to acute myeloid leukaemia (AML)
Set panel types to: GMS Rare Disease
Inherited pancreatic cancer v0.0 Ellen McDonagh Added Panel Inherited pancreatic cancer
Set panel types to: GMS Rare Disease
Inherited predisposition to GIST v0.0 Ellen McDonagh Added Panel Inherited predisposition to GIST
Set panel types to: GMS Rare Disease
Familial melanoma v0.0 Ellen McDonagh Added Panel Familial melanoma
Set panel types to: GMS Rare Disease
Inherited renal cancer v0.0 Ellen McDonagh Added Panel Inherited renal cancer
Set panel types to: GMS Rare Disease
Cytopenia - Fanconi breakage testing indicated v0.0 Ellen McDonagh Added Panel Cytopenia - Fanconi breakage testing indicated
Set panel types to: GMS Rare Disease
Cytopenia - NOT Fanconi anaemia v0.0 Ellen McDonagh Added Panel Cytopenia - NOT Fanconi anaemia
Set panel types to: GMS Rare Disease
Rare anaemia v0.0 Ellen McDonagh Added Panel Rare anaemia
Set panel types to: GMS Rare Disease
Combined factor V and VIII deficiency v0.0 Ellen McDonagh Added Panel Combined factor V and VIII deficiency
Set panel types to: GMS Rare Disease
Thrombophilia v0.0 Ellen McDonagh Added Panel Thrombophilia
Set panel types to: GMS Rare Disease
Genetic epilepsy syndromes v0.897 GOSR2 Louise Daugherty Added comment: Comment on phenotypes: Added phenotypes suggested from expert review that indicate relevance to inclusion on the Genetic Epilepsy Syndromes panel
Genetic epilepsy syndromes v0.897 GOSR2 Louise Daugherty Phenotypes for gene: GOSR2 were changed from to Epilepsy, progressive myoclonic 6, 614018
Iron metabolism disorders v0.0 Ellen McDonagh Added Panel Iron metabolism disorders
Set panel types to: GMS Rare Disease
Genetic epilepsy syndromes v0.896 GOSR2 Louise Daugherty Added comment: Comment on mode of inheritance: added MOI suggested by external review, confirmed with OMIM/publications
Genetic epilepsy syndromes v0.896 GOSR2 Louise Daugherty Mode of inheritance for gene: GOSR2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Intestinal failure v0.0 Ellen McDonagh Added Panel Intestinal failure
Set panel types to: GMS Rare Disease
Non-acute porphyrias v0.0 Ellen McDonagh Added Panel Non-acute porphyrias
Set panel types to: GMS Rare Disease
Congenital fibrosis of the extraocular muscles v0.0 Ellen McDonagh Added Panel Congenital fibrosis of the extraocular muscles
Set panel types to: GMS Rare Disease
Albinism or congenital nystagmus v0.0 Ellen McDonagh Added Panel Albinism or congenital nystagmus
Set panel types to: GMS Rare Disease
Aniridia v0.0 Ellen McDonagh Added Panel Aniridia
Set panel types to: GMS Rare Disease
Structural eye disease v0.0 Ellen McDonagh Added Panel Structural eye disease
Set panel types to: GMS Rare Disease
Confirmed Fanconi anaemia or Bloom syndrome v0.0 Ellen McDonagh Added Panel Confirmed Fanconi anaemia or Bloom syndrome
Set panel types to: GMS Rare Disease
Common craniosynostosis syndromes v0.0 Ellen McDonagh Added Panel Common craniosynostosis syndromes
Set panel types to: GMS Rare Disease
Progressive cardiac conduction disease v0.0 Ellen McDonagh Added Panel Progressive cardiac conduction disease
Set panel types to: GMS Rare Disease
Paediatric or syndromic cardiomyopathy v0.0 Ellen McDonagh Added Panel Paediatric or syndromic cardiomyopathy
Set panel types to: GMS Rare Disease
Inherited polyposis v0.0 Ellen McDonagh Added Panel Inherited polyposis
Set panel types to: GMS Rare Disease
Inherited MMR deficiency (Lynch syndrome) v0.0 Ellen McDonagh Added Panel Inherited MMR deficiency (Lynch syndrome)
Set panel types to: GMS Rare Disease
Amyloidosis with no identifiable cause v0.0 Ellen McDonagh Added Panel Amyloidosis with no identifiable cause
Set panel types to: GMS Rare Disease
Paediatric disorders - additional genes v0.3 Ellen McDonagh Panel status changed from internal to public
Congenital hypothyroidism v1.4 Ellen McDonagh Panel name changed from Congenital hypothyroidism or thyroid agenesis to Congenital hypothyroidism
List of related panels changed from Congenital hypothyroidism to Congenital hypothyroidism or thyroid agenesis
Congenital hypothyroidism v1.3 Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Malformations of cortical development v1.161 Ellen McDonagh List of related panels changed from to
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Arthrogryposis v2.30 Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Genetic epilepsy syndromes v0.895 Ellen McDonagh Panel name changed from Genetic Epilepsy Syndromes to Genetic epilepsy syndromes
List of related panels changed from Epilepsy Plus;Epilepsy plus other features to Epilepsy Plus; Epilepsy plus other features; Genetic Epilepsy Syndromes
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Cystic kidney disease v1.30 Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Rare multisystem ciliopathy disorders v1.78 Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Distal myopathies v1.7 Ellen McDonagh List of related panels changed from to
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Paediatric motor neuronopathies v1.15 Ellen McDonagh List of related panels changed from to
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Intracerebral calcification disorders v1.11 Ellen McDonagh List of related panels changed from to
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Familial dysautonomia v1.5 Ellen McDonagh List of related panels changed from to
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Familial cerebral small vessel disease v1.4 Ellen McDonagh List of related panels changed from to
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Brugada syndrome v1.10 KCNH2 Jules Hancox reviewed gene: KCNH2: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 16043162, 19174314, 18692916; Phenotypes: Brugada syndrome, long QT syndrome, short QT syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Short QT syndrome v0.9 LRP5 Jules Hancox gene: LRP5 was added
gene: LRP5 was added to Short QT syndrome. Sources: Literature
Mode of inheritance for gene: LRP5 was set to Unknown
Publications for gene: LRP5 were set to PMID: 30309679
Phenotypes for gene: LRP5 were set to short qt
Mode of pathogenicity for gene: LRP5 was set to Other
Review for gene: LRP5 was set to RED
Added comment: The evidence here comes from animal model of LRP5 knockout, which results in a short QT interval via modulation of calcium channel degradation. So, in principle, this shows a novel modulator of repolarization that could be implicated in SQTS. Yet to be seen patients.
Sources: Literature
Gastrointestinal neuromuscular disorders v1.8 Ellen McDonagh Panel name changed from Neonatal and familial gastrointestinal neuromuscular disorders to Gastrointestinal neuromuscular disorders
List of related panels changed from Infantile pseudo-obstruction; Early onset or familial intestinal pseudo obstruction to Neonatal and familial gastrointestinal neuromuscular disorders; Infantile pseudo-obstruction; Early onset or familial intestinal pseudo obstruction
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Familial pulmonary fibrosis v1.4 Ellen McDonagh List of related panels changed from to
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Familial non syndromic congenital heart disease v1.34 Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Extreme early-onset hypertension v1.9 Ellen McDonagh List of related panels changed from to
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Genetic epilepsy syndromes v0.894 IKBKG Ivone Leong Phenotypes for gene: IKBKG were changed from to Incontinentia pigmenti, 308300
Genetic epilepsy syndromes v0.893 HSPD1 Ivone Leong Marked gene: HSPD1 as ready
Genetic epilepsy syndromes v0.893 HSPD1 Ivone Leong Added comment: Comment when marking as ready: Leukodystrophy, hypomyelinating, 4 is associated with the gene on OMIM and Gene2Phenotype. However, there are only 2 reported families with variants in this gene. In one large family (PMID:18571143) 6 of 10 affected members have seizures. In another study (PMID:30083362) one patient with a variant in this gene has seizures.
Genetic epilepsy syndromes v0.893 HSPD1 Ivone Leong Gene: hspd1 has been classified as Amber List (Moderate Evidence).
Primary ovarian insufficiency v1.13 Ellen McDonagh Panel name changed from Early onset familial premature ovarian insufficiency to Primary ovarian insufficiency
List of related panels changed from Early onset familial premature ovarian failure to Early onset familial premature ovarian insufficiency; Early onset familial premature ovarian failure
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Genetic epilepsy syndromes v0.893 HSPD1 Ivone Leong Tag watchlist tag was added to gene: HSPD1.
Monogenic nephrogenic diabetes insipidus v1.7 Ellen McDonagh Panel name changed from monogenic nephrogenic diabetes insipidus to Monogenic nephrogenic diabetes insipidus
List of related panels changed from Monogenic nephrogenic diabetes insipidus to monogenic nephrogenic diabetes insipidus
Genetic epilepsy syndromes v0.893 HSPD1 Ivone Leong Publications for gene: HSPD1 were set to
Monogenic nephrogenic diabetes insipidus v1.6 Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Rhabdomyolysis and metabolic muscle disorders v1.22 Ellen McDonagh List of related panels changed from to
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Limb disorders v0.276 Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Clefting v1.33 Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
CAKUT v1.28 Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Segmental overgrowth disorders v1.4 Ellen McDonagh Panel name changed from Regional overgrowth disorders to Segmental overgrowth disorders
List of related panels changed from to Regional overgrowth disorders
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
End-stage renal disease - childhood onset v1.20 Ellen McDonagh Panel name changed from Unexplained kidney failure in young people to End-stage renal disease - childhood onset
List of related panels changed from Familial IgA nephropathy and IgA vasculitis to Unexplained kidney failure in young people; Familial IgA nephropathy and IgA vasculitis
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Cerebral vascular malformations v1.35 Ellen McDonagh Panel name changed from Cerebrovascular disorders to Cerebral vascular malformations
List of related panels changed from Vein of Galen malformation; Cerebral vascular malformations; Cerebral arteriovenous malformations; Moyamoya disease to Cerebrovascular disorders; Vein of Galen malformation; Cerebral arteriovenous malformations; Moyamoya disease
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Genetic epilepsy syndromes v0.892 HSPD1 Ivone Leong Mode of inheritance for gene: HSPD1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.891 HSPD1 Ivone Leong Phenotypes for gene: HSPD1 were changed from to Leukodystrophy, hypomyelinating, 4, 612233
Hereditary neuropathy v1.26 Ellen McDonagh Panel name changed from Charcot-Marie-Tooth disease to Hereditary neuropathy
List of related panels changed from to Charcot-Marie-Tooth disease
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Ehlers Danlos syndromes v1.34 Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Genetic epilepsy syndromes v0.890 HSD17B4 Ivone Leong Marked gene: HSD17B4 as ready
Genetic epilepsy syndromes v0.890 HSD17B4 Ivone Leong Gene: hsd17b4 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.890 HSD17B4 Ivone Leong Classified gene: HSD17B4 as Green List (high evidence)
Genetic epilepsy syndromes v0.890 HSD17B4 Ivone Leong Added comment: Comment on list classification: Promoted from amber to green as 3+ unrelated patients reported with D-bifunctional protein deficiency have variants in this gene and also have seizures. D-bifunctional protein deficiency is conformed to be associated with this gene on both OMIM and Gene2Phenotype.
Genetic epilepsy syndromes v0.890 HSD17B4 Ivone Leong Gene: hsd17b4 has been classified as Green List (High Evidence).
Tumour predisposition - childhood onset v1.20 Ellen McDonagh Panel name changed from Paediatric congenital malformation-dysmorphism-tumour syndrome to Tumour predisposition - childhood onset
List of related panels changed from Paediatric congenital malformation-dysmorphism-tumour syndromes ; Paediatric congenital malformation-dysmorphism-tumour sydromes; Paediatric congenital malformation-dysmorphism-tumour syndrome to Paediatric congenital malformation-dysmorphism-tumour syndrome; Paediatric congenital malformation-dysmorphism-tumour syndromes; Paediatric congenital malformation-dysmorphism-tumour sydromes; Paediatric congenital malformation-dysmorphism-tumour syndrome
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Primary immunodeficiency v1.28 Ellen McDonagh Panel name changed from Primary immunodeficiency disorders to Primary immunodeficiency
List of related panels changed from A- or hypo-gammaglobulinaemia; Congenital neutropaenia; Agranulocytosis; Combined B and T cell defect; Inherited complement deficiency; SCID; Primary immune disorder; Primary immunodeficiency; A-gammaglobulinaemia; Agammaglobulinaemia; hypo-gammaglobulinaemia; hypogammaglobulinemia; immune deficiency syndromes; Severe combined immunodeficiency; Congenital neutopenia; Familial haemophagocytic lymphohistiocytic disorders; Familial hemophagocytic lymphohistiocytic disorders; PID; Sepsis; Disseminated non-tuberculous mycobacterial infection to Primary immunodeficiency disorders; A- or hypo-gammaglobulinaemia; Congenital neutropaenia; Agranulocytosis; Combined B and T cell defect; Inherited complement deficiency; SCID; Primary immune disorder; Primary immunodeficiency; A-gammaglobulinaemia; Agammaglobulinaemia; hypo-gammaglobulinaemia; hypogammaglobulinemia; immune deficiency syndromes; Severe combined immunodeficiency; Congenital neutopenia; Familial haemophagocytic lymphohistiocytic disorders; Familial hemophagocytic lymphohistiocytic disorders; PID; Sepsis; Disseminated non-tuberculous mycobacterial infection
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Genetic epilepsy syndromes v0.889 HSD17B4 Ivone Leong Publications for gene: HSD17B4 were set to 9345094; 9482850; 9915948; 11743515
Retinal disorders v1.87 Ellen McDonagh Panel name changed from Posterior segment abnormalities to Retinal disorders
List of related panels changed from Cone Dysfunction Syndrome; Developmental macular and foveal dystrophy; Inherited macular dystrophy; Leber Congenital Amaurosis Early-Onset Severe Retinal Dystrophy; Leber Congenital Amaurosis / Early-Onset Severe Retinal Dystrophy; Leber Congenital Amaurosis or Early-Onset Severe Retinal Dystrophy; Rod Dysfunction Syndrome; Rod-cone dystrophy; Familial exudative vitreoretinopathy; Familial exudative retinopathy to Posterior segment abnormalities; Cone Dysfunction Syndrome; Developmental macular and foveal dystrophy; Inherited macular dystrophy; Leber Congenital Amaurosis Early-Onset Severe Retinal Dystrophy; Leber Congenital Amaurosis / Early-Onset Severe Retinal Dystrophy; Leber Congenital Amaurosis or Early-Onset Severe Retinal Dystrophy; Rod Dysfunction Syndrome; Rod-cone dystrophy; Familial exudative vitreoretinopathy; Familial exudative retinopathy
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Cataracts v1.21 Ellen McDonagh List of related panels changed from to
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Genetic epilepsy syndromes v0.888 HSD17B4 Ivone Leong Publications for gene: HSD17B4 were set to
Hereditary spastic paraplegia v1.68 Ellen McDonagh List of related panels changed from to
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Endocrine neoplasia v1.7 Ellen McDonagh Panel name changed from Multiple endocrine neoplasia type 1 to Endocrine neoplasia
List of related panels changed from Multiple endocrine tumours to Multiple endocrine tumours; Multiple endocrine neoplasia type 1
Movement disorders - childhood onset v0.4 Ellen McDonagh Panel status changed from internal to public
Movement disorders - childhood onset v0.3 Ellen McDonagh Changed child panels to:
Renal and urinary tract disorders v0.7 Ellen McDonagh Panel status changed from internal to public
Renal and urinary tract disorders v0.6 Ellen McDonagh Changed child panels to:
Cerebral malformations v0.3 Ellen McDonagh Panel status changed from internal to public
Changed child panels to:
Arthrogryposis - broad panel v0.2 Ellen McDonagh Panel status changed from internal to public
Changed child panels to:
Hypotonic infant v0.4 Ellen McDonagh Panel status changed from internal to public
Changed child panels to:
Epilepsy - early onset or syndromic v0.288 Ellen McDonagh Panel status changed from internal to public
Changed child panels to:
Hereditary ataxia and cerebellar anomalies - childhood onset v0.3 Ellen McDonagh Panel status changed from internal to public
Changed child panels to:
Cystic renal disease v0.4 Ellen McDonagh Panel status changed from internal to public
Changed child panels to:
Paediatric disorders v0.6 Ellen McDonagh Panel status changed from internal to public
Paediatric disorders v0.5 Ellen McDonagh Changed child panels to:
White matter disorders - childhood onset v0.4 Ellen McDonagh Panel status changed from internal to public
White matter disorders - childhood onset v0.3 Ellen McDonagh Changed child panels to:
Panel types changed to GMS Rare Disease Virtual
Intellectual disability v2.534 Ellen McDonagh 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 to Coarse facial features including Coffin-Siris-like disorders; ID; Moderate; severe or profound intellectual disability; Schizophrenia plus additional features
Genetic epilepsy syndromes v0.887 HSD17B4 Ivone Leong Mode of inheritance for gene: HSD17B4 was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.886 HSD17B4 Ivone Leong Phenotypes for gene: HSD17B4 were changed from to D-bifunctional protein deficiency, 261515
Genetic epilepsy syndromes v0.885 HRAS Ivone Leong Marked gene: HRAS as ready
Genetic epilepsy syndromes v0.885 HRAS Ivone Leong Gene: hras has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.885 HRAS Ivone Leong Publications for gene: HRAS were set to
Genetic epilepsy syndromes v0.884 HRAS Ivone Leong Classified gene: HRAS as Green List (high evidence)
Genetic epilepsy syndromes v0.884 HRAS Ivone Leong Added comment: Comment on list classification: Promoted from amber to green. There are 3+ cases reporting of patients with Costello syndrome who have seizures (PMID: 28337834, 27195699, 26888048, 22926243) and all patients have HRAS heterozygous variants.

It is also confirmed as being associated with Costello syndrome on OMIM and Gene2Phenotype.
Genetic epilepsy syndromes v0.884 HRAS Ivone Leong Gene: hras has been classified as Green List (High Evidence).
Intellectual disability v2.533 Ellen McDonagh List of related panels changed from Coarse facial features including Coffin-Siris-like disorders; ID;Moderate; severe or profound intellectual disability to Coarse facial features including Coffin-Siris-like disorders;ID;Moderate; severe or profound intellectual disability;Schizophrenia plus additional features
Genetic epilepsy syndromes v0.883 FKRP Louise Daugherty Added comment: Comment on phenotypes: added phenotype suggested from external reviewer
Genetic epilepsy syndromes v0.883 FKRP Louise Daugherty Phenotypes for gene: FKRP were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 5, 613153
Short QT syndrome v0.9 Sarah Leigh List of related panels changed from to
Short QT syndrome v0.8 KCNQ1 Olivia Niblock reviewed gene: KCNQ1: Rating: AMBER; Mode of pathogenicity: None; Publications: 15159330; Phenotypes: Idiopathic Ventricular Fibrillation, Short QT-interval syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Short QT syndrome v0.8 KCNQ1 Reviewer Test Deleted their review
Brugada syndrome v1.10 KCNE5 Sarah Leigh Added comment: Comment on publications: PMID 29350269: Report of a de novo variant in case of sudden cardiac death (female age 5), with atrial fibrillation and Brugada syndrome. PMID 30289750: "Kcne5 knockout ( Kcne5-/0) mice have ventricular premature beats, increased susceptibility to induction of polymorphic ventricular tachycardia (60 vs. 24% in Kcne5+/0 mice), and 10% shorter ventricular refractory period. The findings represent the first reported native role for Kcne5 and the first demonstrated Kcne regulation of KV2.1 in mouse heart. Increased KV current is a manifestation of KCNE5 disruption that is most likely common to both mouse and human hearts, providing a plausible mechanistic basis for human KCNE5-linked."
Brugada syndrome v1.10 KCNE5 Sarah Leigh Publications for gene: KCNE5 were set to 29350269
Short QT syndrome v0.8 KCNE5 Sarah Leigh edited their review of gene: KCNE5: Changed rating: RED
Short QT syndrome v0.8 KCNE5 Sarah Leigh Phenotypes for gene: KCNE5 were changed from to atrial fibrillation; Brugada syndrome
Short QT syndrome v0.7 KCNE5 Sarah Leigh Added comment: Comment on publications: Report of a de novo variant in case of sudden cardiac death (female age 5), with atrial fibrillation and Brugada syndrome.
Short QT syndrome v0.7 KCNE5 Sarah Leigh Publications for gene: KCNE5 were set to
Brugada syndrome v1.9 KCNE5 Sarah Leigh Phenotypes for gene: KCNE5 were changed from to atrial fibrillation; Brugada syndrome
Brugada syndrome v1.8 KCNE5 Sarah Leigh Added comment: Comment on publications: Report of a de novo variant in case of sudden cardiac death (female age 5), with atrial fibrillation and Brugada syndrome.
Brugada syndrome v1.8 KCNE5 Sarah Leigh Publications for gene: KCNE5 were set to
Short QT syndrome v0.6 CACNA2D1 Sarah Leigh Classified gene: CACNA2D1 as Red List (low evidence)
Short QT syndrome v0.6 CACNA2D1 Sarah Leigh Gene: cacna2d1 has been classified as Red List (Low Evidence).
Short QT syndrome v0.5 CACNA2D1 Sarah Leigh Publications for gene: CACNA2D1 were set to PMID: 21383000; 29759541; 29697308
Short QT syndrome v0.4 RANGRF Sarah Leigh reviewed gene: RANGRF: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Short QT syndrome v0.4 PKP2 Sarah Leigh reviewed gene: PKP2: Rating: RED; Mode of pathogenicity: ; Publications: 24352520, 26888179; Phenotypes: ; Mode of inheritance: Unknown
Short QT syndrome v0.4 NOS1AP Sarah Leigh reviewed gene: NOS1AP: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Short QT syndrome v0.4 KCNQ1 Sarah Leigh reviewed gene: KCNQ1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Short QT syndrome v0.4 KCNJ8 Sarah Leigh reviewed gene: KCNJ8: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Short QT syndrome v0.4 KCNJ5 Sarah Leigh reviewed gene: KCNJ5: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Short QT syndrome v0.4 KCNJ2 Sarah Leigh reviewed gene: KCNJ2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Short QT syndrome v0.4 KCNH2 Sarah Leigh reviewed gene: KCNH2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Short QT syndrome v0.4 KCNE5 Sarah Leigh reviewed gene: KCNE5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Short QT syndrome v0.4 KCNE3 Sarah Leigh reviewed gene: KCNE3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Short QT syndrome v0.4 KCNE2 Sarah Leigh reviewed gene: KCNE2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Short QT syndrome v0.4 KCNE1 Sarah Leigh reviewed gene: KCNE1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Short QT syndrome v0.4 KCND3 Sarah Leigh reviewed gene: KCND3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Short QT syndrome v0.4 HCN4 Sarah Leigh reviewed gene: HCN4: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Short QT syndrome v0.4 GPD1L Sarah Leigh reviewed gene: GPD1L: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Short QT syndrome v0.4 DLG1 Sarah Leigh reviewed gene: DLG1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Short QT syndrome v0.4 CAV3 Sarah Leigh reviewed gene: CAV3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Short QT syndrome v0.4 CALM3 Sarah Leigh reviewed gene: CALM3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Short QT syndrome v0.4 CALM2 Sarah Leigh reviewed gene: CALM2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Short QT syndrome v0.4 CALM1 Sarah Leigh reviewed gene: CALM1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Short QT syndrome v0.4 CACNB2 Sarah Leigh reviewed gene: CACNB2: Rating: AMBER; Mode of pathogenicity: ; Publications: 17224476; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Short QT syndrome v0.4 CACNA2D1 Sarah Leigh reviewed gene: CACNA2D1: Rating: RED; Mode of pathogenicity: ; Publications: 21383000; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Short QT syndrome v0.4 CACNA1C Sarah Leigh reviewed gene: CACNA1C: Rating: GREEN; Mode of pathogenicity: ; Publications: 30027834, 30279520; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Short QT syndrome v0.4 ANK2 Sarah Leigh reviewed gene: ANK2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Short QT syndrome v0.4 ALG10 Sarah Leigh reviewed gene: ALG10: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Short QT syndrome v0.4 AKAP9 Sarah Leigh reviewed gene: AKAP9: Rating: RED; Mode of pathogenicity: ; Publications: 18093912; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Short QT syndrome v0.4 ABCC9 Sarah Leigh reviewed gene: ABCC9: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic epilepsy syndromes v0.882 HRAS Ivone Leong Mode of inheritance for gene: HRAS was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic epilepsy syndromes v0.881 HRAS Ivone Leong Phenotypes for gene: HRAS were changed from Costello syndrome, 218040 to Costello syndrome, 218040; Schimmelpenning-Feuerstein-Mims syndrome, 218040
Genetic epilepsy syndromes v0.880 HRAS Ivone Leong Phenotypes for gene: HRAS were changed from to Costello syndrome, 218040
Genetic epilepsy syndromes v0.879 HEXA Ivone Leong Marked gene: HEXA as ready
Genetic epilepsy syndromes v0.879 HEXA Ivone Leong Gene: hexa has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.879 HEXA Ivone Leong Classified gene: HEXA as Green List (high evidence)
Genetic epilepsy syndromes v0.879 HEXA Ivone Leong Added comment: Comment on list classification: Promoted from Amber to Green as seizures is a phenotype of
Tay-Sachs disease in accordance with the review by Zornitza Stark (Australian Genomics). Tay-Sachs disease is confirmed to be associated with this gene by both OMIM and Gene2Phenotype.
Genetic epilepsy syndromes v0.879 HEXA Ivone Leong Gene: hexa has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.878 HEXA Ivone Leong Mode of inheritance for gene: HEXA was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.877 HEXA Ivone Leong Mode of inheritance for gene: HEXA was changed from to BIALLELIC, autosomal or pseudoautosomal
Short QT syndrome v0.3 SLC4A3 Sarah Leigh Publications for gene: SLC4A3 were set to PMID: 29167417; 29697308
Genetic epilepsy syndromes v0.876 HEXA Ivone Leong Phenotypes for gene: HEXA were changed from to Tay-Sachs disease, 272800
Genetic epilepsy syndromes v0.875 HEPACAM Ivone Leong Marked gene: HEPACAM as ready
Genetic epilepsy syndromes v0.875 HEPACAM Ivone Leong Gene: hepacam has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.875 HEPACAM Ivone Leong Classified gene: HEPACAM as Green List (high evidence)
Genetic epilepsy syndromes v0.875 HEPACAM Ivone Leong Added comment: Comment on list classification: Promoted from amber to green based on evidence in the literature. One study (PMID: 21419380) reported 8 families with 10 patients with either homozygous or compound heterozygous variants in this gene having epilepsy. Another study (PMID: 27389245) reported on a patient with a homozygous variant in this gene having generalized tonic-clonic seizure.
Megalencephalic leukoencephalopathy with subcortical cysts 2A confirmed to be associated with this gene on OMIM but not Gene2Phenotype.
Genetic epilepsy syndromes v0.875 HEPACAM Ivone Leong Gene: hepacam has been classified as Green List (High Evidence).
Short QT syndrome v0.2 SLC4A3 Sarah Leigh Source Expert Review Green was added to SLC4A3.
Mode of inheritance for gene SLC4A3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Rating Changed from No List (delete) to Green List (high evidence)
Short QT syndrome v0.2 SLC22A5 Sarah Leigh Source Expert Review Green was added to SLC22A5.
Mode of inheritance for gene SLC22A5 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Rating Changed from No List (delete) to Green List (high evidence)
Short QT syndrome v0.2 TRPM4 Sarah Leigh gene: TRPM4 was added
gene: TRPM4 was added to Short QT syndrome. Sources: Brugada syndrome (Version 1.7)
Mode of inheritance for gene: TRPM4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Short QT syndrome v0.2 SNTA1 Sarah Leigh gene: SNTA1 was added
gene: SNTA1 was added to Short QT syndrome. Sources: Long QT syndrome (Version 1.5),Emory Genetics Laboratory
Mode of inheritance for gene: SNTA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Short QT syndrome v0.2 SLMAP Sarah Leigh gene: SLMAP was added
gene: SLMAP was added to Short QT syndrome. Sources: Brugada syndrome (Version 1.7)
Mode of inheritance for gene: SLMAP was set to
Short QT syndrome v0.2 SCN5A Sarah Leigh Source Emory Genetics Laboratory was added to SCN5A.
Source Long QT syndrome (Version 1.5) was added to SCN5A.
Source Expert Review Green was added to SCN5A.
Source Brugada syndrome (Version 1.7) was added to SCN5A.
Mode of inheritance for gene SCN5A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Rating Changed from No List (delete) to Green List (high evidence)
Short QT syndrome v0.2 SCN4B Sarah Leigh gene: SCN4B was added
gene: SCN4B was added to Short QT syndrome. Sources: Long QT syndrome (Version 1.5),Emory Genetics Laboratory
Mode of inheritance for gene: SCN4B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Short QT syndrome v0.2 SCN3B Sarah Leigh gene: SCN3B was added
gene: SCN3B was added to Short QT syndrome. Sources: Brugada syndrome (Version 1.7)
Mode of inheritance for gene: SCN3B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Short QT syndrome v0.2 SCN2B Sarah Leigh gene: SCN2B was added
gene: SCN2B was added to Short QT syndrome. Sources: Brugada syndrome (Version 1.7)
Mode of inheritance for gene: SCN2B was set to
Short QT syndrome v0.2 SCN1B Sarah Leigh gene: SCN1B was added
gene: SCN1B was added to Short QT syndrome. Sources: Brugada syndrome (Version 1.7)
Mode of inheritance for gene: SCN1B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Short QT syndrome v0.2 SCN10A Sarah Leigh Source Brugada syndrome (Version 1.7) was added to SCN10A.
Source Expert Review Red was added to SCN10A.
Mode of inheritance for gene SCN10A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Rating Changed from No List (delete) to Red List (low evidence)
Short QT syndrome v0.2 RYR2 Sarah Leigh gene: RYR2 was added
gene: RYR2 was added to Short QT syndrome. Sources: Long QT syndrome (Version 1.5)
Mode of inheritance for gene: RYR2 was set to Unknown
Short QT syndrome v0.2 RANGRF Sarah Leigh gene: RANGRF was added
gene: RANGRF was added to Short QT syndrome. Sources: Brugada syndrome (Version 1.7)
Mode of inheritance for gene: RANGRF was set to
Short QT syndrome v0.2 PKP2 Sarah Leigh gene: PKP2 was added
gene: PKP2 was added to Short QT syndrome. Sources: Brugada syndrome (Version 1.7)
Mode of inheritance for gene: PKP2 was set to Unknown
Short QT syndrome v0.2 NOS1AP Sarah Leigh gene: NOS1AP was added
gene: NOS1AP was added to Short QT syndrome. Sources: Long QT syndrome (Version 1.5)
Mode of inheritance for gene: NOS1AP was set to
Short QT syndrome v0.2 KCNQ1 Sarah Leigh Source Emory Genetics Laboratory was added to KCNQ1.
Source Long QT syndrome (Version 1.5) was added to KCNQ1.
Source Expert Review Green was added to KCNQ1.
Source UKGTN was added to KCNQ1.
Source Radboud University Medical Center, Nijmegen was added to KCNQ1.
Added phenotypes Short QT syndrome 2 609621 for gene: KCNQ1
Rating Changed from No List (delete) to Green List (high evidence)
Short QT syndrome v0.2 KCNJ8 Sarah Leigh Source Brugada syndrome (Version 1.7) was added to KCNJ8.
Source Expert Review Red was added to KCNJ8.
Rating Changed from No List (delete) to Red List (low evidence)
Short QT syndrome v0.2 KCNJ5 Sarah Leigh gene: KCNJ5 was added
gene: KCNJ5 was added to Short QT syndrome. Sources: Long QT syndrome (Version 1.5)
Mode of inheritance for gene: KCNJ5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Short QT syndrome v0.2 KCNJ2 Sarah Leigh Source Emory Genetics Laboratory was added to KCNJ2.
Source Long QT syndrome (Version 1.5) was added to KCNJ2.
Source Expert Review Green was added to KCNJ2.
Source UKGTN was added to KCNJ2.
Source Radboud University Medical Center, Nijmegen was added to KCNJ2.
Added phenotypes Short QT syndrome 3 609622 for gene: KCNJ2
Rating Changed from No List (delete) to Green List (high evidence)
Short QT syndrome v0.2 KCNH2 Sarah Leigh Source UKGTN was added to KCNH2.
Source Radboud University Medical Center, Nijmegen was added to KCNH2.
Source Emory Genetics Laboratory was added to KCNH2.
Source Expert Review Green was added to KCNH2.
Source Brugada syndrome (Version 1.7) was added to KCNH2.
Source Long QT syndrome (Version 1.5) was added to KCNH2.
Mode of inheritance for gene KCNH2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Added phenotypes Short QT syndrome 1 609620 for gene: KCNH2
Rating Changed from No List (delete) to Green List (high evidence)
Short QT syndrome v0.2 KCNE5 Sarah Leigh gene: KCNE5 was added
gene: KCNE5 was added to Short QT syndrome. Sources: Brugada syndrome (Version 1.7)
Mode of inheritance for gene: KCNE5 was set to
Short QT syndrome v0.2 KCNE3 Sarah Leigh gene: KCNE3 was added
gene: KCNE3 was added to Short QT syndrome. Sources: Long QT syndrome (Version 1.5),Brugada syndrome (Version 1.7)
Mode of inheritance for gene: KCNE3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Short QT syndrome v0.2 KCNE2 Sarah Leigh gene: KCNE2 was added
gene: KCNE2 was added to Short QT syndrome. Sources: Long QT syndrome (Version 1.5),Emory Genetics Laboratory
Mode of inheritance for gene: KCNE2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Short QT syndrome v0.2 KCNE1 Sarah Leigh gene: KCNE1 was added
gene: KCNE1 was added to Short QT syndrome. Sources: Long QT syndrome (Version 1.5),Emory Genetics Laboratory
Mode of inheritance for gene: KCNE1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Short QT syndrome v0.2 KCND3 Sarah Leigh gene: KCND3 was added
gene: KCND3 was added to Short QT syndrome. Sources: Brugada syndrome (Version 1.7)
Mode of inheritance for gene: KCND3 was set to
Short QT syndrome v0.2 HCN4 Sarah Leigh gene: HCN4 was added
gene: HCN4 was added to Short QT syndrome. Sources: Brugada syndrome (Version 1.7)
Mode of inheritance for gene: HCN4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Short QT syndrome v0.2 GPD1L Sarah Leigh gene: GPD1L was added
gene: GPD1L was added to Short QT syndrome. Sources: Brugada syndrome (Version 1.7)
Mode of inheritance for gene: GPD1L was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Short QT syndrome v0.2 DLG1 Sarah Leigh gene: DLG1 was added
gene: DLG1 was added to Short QT syndrome. Sources: Brugada syndrome (Version 1.7)
Mode of inheritance for gene: DLG1 was set to
Short QT syndrome v0.2 CAV3 Sarah Leigh gene: CAV3 was added
gene: CAV3 was added to Short QT syndrome. Sources: Emory Genetics Laboratory,Long QT syndrome (Version 1.5),Brugada syndrome (Version 1.7)
Mode of inheritance for gene: CAV3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Short QT syndrome v0.2 CALM3 Sarah Leigh gene: CALM3 was added
gene: CALM3 was added to Short QT syndrome. Sources: Long QT syndrome (Version 1.5)
Mode of inheritance for gene: CALM3 was set to
Short QT syndrome v0.2 CALM2 Sarah Leigh gene: CALM2 was added
gene: CALM2 was added to Short QT syndrome. Sources: Long QT syndrome (Version 1.5)
Mode of inheritance for gene: CALM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Short QT syndrome v0.2 CALM1 Sarah Leigh gene: CALM1 was added
gene: CALM1 was added to Short QT syndrome. Sources: Long QT syndrome (Version 1.5),Emory Genetics Laboratory
Mode of inheritance for gene: CALM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Short QT syndrome v0.2 CACNB2 Sarah Leigh Source Brugada syndrome (Version 1.7) was added to CACNB2.
Source Expert Review Green was added to CACNB2.
Source UKGTN was added to CACNB2.
Mode of inheritance for gene CACNB2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Added phenotypes Brugada syndrome 4 611876; Short QT syndrome 5 for gene: CACNB2
Rating Changed from No List (delete) to Green List (high evidence)
Short QT syndrome v0.2 CACNA2D1 Sarah Leigh Source Brugada syndrome (Version 1.7) was added to CACNA2D1.
Source Expert Review Green was added to CACNA2D1.
Source UKGTN was added to CACNA2D1.
Mode of inheritance for gene CACNA2D1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Added phenotypes Short QT syndrome 6 for gene: CACNA2D1
Rating Changed from No List (delete) to Green List (high evidence)
Short QT syndrome v0.2 CACNA1C Sarah Leigh Source Emory Genetics Laboratory was added to CACNA1C.
Source Long QT syndrome (Version 1.5) was added to CACNA1C.
Source Expert Review Green was added to CACNA1C.
Source UKGTN was added to CACNA1C.
Source Brugada syndrome (Version 1.7) was added to CACNA1C.
Added phenotypes Brugada syndrome 3 611875 for gene: CACNA1C
Rating Changed from No List (delete) to Green List (high evidence)
Short QT syndrome v0.2 ANK2 Sarah Leigh gene: ANK2 was added
gene: ANK2 was added to Short QT syndrome. Sources: Emory Genetics Laboratory,Long QT syndrome (Version 1.5),Brugada syndrome (Version 1.7)
Mode of inheritance for gene: ANK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ANK2 were set to Cardiac arrhythmia, ankyrin-B-related 600919; Long QT syndrome 4 600919
Short QT syndrome v0.2 ALG10 Sarah Leigh gene: ALG10 was added
gene: ALG10 was added to Short QT syndrome. Sources: Long QT syndrome (Version 1.5)
Mode of inheritance for gene: ALG10 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: ALG10 were set to {Long QT syndrome, acquired, reduced susceptibility to} 613688
Short QT syndrome v0.2 AKAP9 Sarah Leigh gene: AKAP9 was added
gene: AKAP9 was added to Short QT syndrome. Sources: Long QT syndrome (Version 1.5),Emory Genetics Laboratory
Mode of inheritance for gene: AKAP9 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: AKAP9 were set to ?Long QT syndrome-11 611820
Short QT syndrome v0.2 ABCC9 Sarah Leigh Source Brugada syndrome (Version 1.7) was added to ABCC9.
Source Expert Review Red was added to ABCC9.
Mode of inheritance for gene ABCC9 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Rating Changed from No List (delete) to Red List (low evidence)
Intellectual disability v2.532 TBR1 Konstantinos Varvagiannis reviewed gene: TBR1: Rating: AMBER; Mode of pathogenicity: None; Publications: 30268909, 25356899, 23160955, 22495311, 30250039; Phenotypes: Intellectual disability, Autism, Abnormal cortical gyration; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Genetic epilepsy syndromes v0.874 EFHC1 Sarah Leigh Marked gene: EFHC1 as ready
Genetic epilepsy syndromes v0.874 EFHC1 Sarah Leigh Gene: efhc1 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v0.874 EFHC1 Sarah Leigh Classified gene: EFHC1 as Amber List (moderate evidence)
Genetic epilepsy syndromes v0.874 EFHC1 Sarah Leigh Added comment: Comment on list classification: As this gene is associated with susceptibility to juvenile absence epilepsy (MIM 607631) and juvenile myoclonic epilepsy 1 (MIM 254770), EFHC1 has been rated at amber in consultation with Arianna Tucci (GEL Clinical Fellow).
Genetic epilepsy syndromes v0.874 EFHC1 Sarah Leigh Gene: efhc1 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v0.873 HEPACAM Ivone Leong Publications for gene: HEPACAM were set to
Genetic epilepsy syndromes v0.872 PAFAH1B1 Eleanor Williams Marked gene: PAFAH1B1 as ready
Genetic epilepsy syndromes v0.872 PAFAH1B1 Eleanor Williams Added comment: Comment when marking as ready: Sufficient cases with PAFAH1B1 variants in Lissencephaly 1 and reports of seizures.
Genetic epilepsy syndromes v0.872 PAFAH1B1 Eleanor Williams Gene: pafah1b1 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.872 PAFAH1B1 Eleanor Williams Phenotypes for gene: PAFAH1B1 were changed from to Lissencephaly 1 607432
Genetic epilepsy syndromes v0.871 PAFAH1B1 Eleanor Williams Publications for gene: PAFAH1B1 were set to
Genetic epilepsy syndromes v0.870 PAFAH1B1 Eleanor Williams Mode of inheritance for gene: PAFAH1B1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic epilepsy syndromes v0.869 PAFAH1B1 Eleanor Williams Classified gene: PAFAH1B1 as Green List (high evidence)
Genetic epilepsy syndromes v0.869 PAFAH1B1 Eleanor Williams Added comment: Comment on list classification: Numerous cases of variants in the PAFAH1B1 gene in patients with Lissencephaly 1 and reporting seizures.
Genetic epilepsy syndromes v0.869 PAFAH1B1 Eleanor Williams Gene: pafah1b1 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.868 PAFAH1B1 Eleanor Williams commented on gene: PAFAH1B1
Genetic epilepsy syndromes v0.868 OPHN1 Eleanor Williams Marked gene: OPHN1 as ready
Genetic epilepsy syndromes v0.868 OPHN1 Eleanor Williams Added comment: Comment when marking as ready: 3 cases of patients with SNVs in OPHN1 and a phenotype that includes epilepsy/seizures. Carrier females may show milder phenotype.
Genetic epilepsy syndromes v0.868 OPHN1 Eleanor Williams Gene: ophn1 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.868 OPHN1 Eleanor Williams Added comment: Comment on mode of inheritance: Note OMIM reports an XLR mode of inheritance. But evidence from PMIDs: 16221952, 29510240 suggest that carrier females can show phenotypic traits although in milder form.
Genetic epilepsy syndromes v0.868 OPHN1 Eleanor Williams Mode of inheritance for gene: OPHN1 was changed from to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Genetic epilepsy syndromes v0.867 OPHN1 Eleanor Williams Classified gene: OPHN1 as Green List (high evidence)
Genetic epilepsy syndromes v0.867 OPHN1 Eleanor Williams Added comment: Comment on list classification: 3 cases of patients with SNVs in OPHN1 and a phenotype that includes epilepsy/seizures. Seizures not seen in every case.
Genetic epilepsy syndromes v0.867 OPHN1 Eleanor Williams Gene: ophn1 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.866 OPHN1 Eleanor Williams Phenotypes for gene: OPHN1 were changed from to Mental retardation, X-linked, with cerebellar hypoplasia and distinctive facial appearance 300486; MENTAL RETARDATION X-LINKED OPHN1-RELATED
Genetic epilepsy syndromes v0.865 OPHN1 Eleanor Williams Publications for gene: OPHN1 were set to
Genetic epilepsy syndromes v0.864 OPHN1 Eleanor Williams commented on gene: OPHN1
Genetic epilepsy syndromes v0.864 HEPACAM Ivone Leong Mode of inheritance for gene: HEPACAM was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.863 HEPACAM Ivone Leong Phenotypes for gene: HEPACAM were changed from to Megalencephalic leukoencephalopathy with subcortical cysts 2A, 613925
Genetic epilepsy syndromes v0.862 OCLN Eleanor Williams Marked gene: OCLN as ready
Genetic epilepsy syndromes v0.862 OCLN Eleanor Williams Added comment: Comment when marking as ready: Sufficient cases with variants in OCLN and seizures reported.
Genetic epilepsy syndromes v0.862 OCLN Eleanor Williams Gene: ocln has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.862 OCLN Eleanor Williams Phenotypes for gene: OCLN were changed from to Pseudo-TORCH syndrome 1 251290
Genetic epilepsy syndromes v0.861 OCLN Eleanor Williams Publications for gene: OCLN were set to
Genetic epilepsy syndromes v0.860 OCLN Eleanor Williams Mode of inheritance for gene: OCLN was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.859 OCLN Eleanor Williams Classified gene: OCLN as Green List (high evidence)
Genetic epilepsy syndromes v0.859 OCLN Eleanor Williams Added comment: Comment on list classification: More than 3 cases/variants reported in OCLN in patients with Pseudo-TORCH syndrome 1. At least 3 families with reports of seizures in newborns.
Genetic epilepsy syndromes v0.859 OCLN Eleanor Williams Gene: ocln has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.858 OCLN Eleanor Williams commented on gene: OCLN
Genetic epilepsy syndromes v0.858 HCFC1 Ivone Leong Marked gene: HCFC1 as ready
Genetic epilepsy syndromes v0.858 HCFC1 Ivone Leong Added comment: Comment when marking as ready: Mental retardation, X-linked 3 is associated with HCFC1 and is confirmed in both OMIM and Gene2Phenotype. >3 unrelated probands have been found to have a mutation in this gene and also have epilepsy.
Genetic epilepsy syndromes v0.858 HCFC1 Ivone Leong Gene: hcfc1 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.858 HCFC1 Ivone Leong Classified gene: HCFC1 as Green List (high evidence)
Genetic epilepsy syndromes v0.858 HCFC1 Ivone Leong Added comment: Comment on list classification: Promoted from amber to green as >3 unrelated probands have been found to have a mutation in this gene and also have epilepsy.
Genetic epilepsy syndromes v0.858 HCFC1 Ivone Leong Gene: hcfc1 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.857 HCFC1 Ivone Leong Publications for gene: HCFC1 were set to
Genetic epilepsy syndromes v0.856 NUBPL Eleanor Williams Marked gene: NUBPL as ready
Genetic epilepsy syndromes v0.856 NUBPL Eleanor Williams Added comment: Comment when marking as ready: Sufficient cases associating NUBPL with Mitochondrial complex I deficiency but not sufficient cases with epilepsy/seizure phenotype to rate this gene green on this panel.
Genetic epilepsy syndromes v0.856 NUBPL Eleanor Williams Gene: nubpl has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v0.856 NUBPL Eleanor Williams Phenotypes for gene: NUBPL were changed from to Mitochondrial complex I deficiency 252010
Genetic epilepsy syndromes v0.855 NUBPL Eleanor Williams Publications for gene: NUBPL were set to
Genetic epilepsy syndromes v0.854 NUBPL Eleanor Williams Mode of inheritance for gene: NUBPL was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.853 NUBPL Eleanor Williams Classified gene: NUBPL as Amber List (moderate evidence)
Genetic epilepsy syndromes v0.853 NUBPL Eleanor Williams Added comment: Comment on list classification: Keeping Amber as only 1 confirmed case of patient with epilepsy
Genetic epilepsy syndromes v0.853 NUBPL Eleanor Williams Gene: nubpl has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v0.852 NUBPL Eleanor Williams commented on gene: NUBPL
Genetic epilepsy syndromes v0.852 HCCS Ivone Leong Marked gene: HCCS as ready
Genetic epilepsy syndromes v0.852 HCCS Ivone Leong Added comment: Comment when marking as ready: 'Linear skin defects with multiple congenital anomalies 1' confirmed in both OMIM and Gene2Phenotype. However, seizures is not a common feature. Only found one patient with who had a seizure (17033964).
Genetic epilepsy syndromes v0.852 HCCS Ivone Leong Gene: hccs has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v0.852 HCCS Ivone Leong Publications for gene: HCCS were set to
White matter disorders and cerebral calcification - narrow panel v0.5 Ellen McDonagh Panel status changed from internal to public
White matter disorders and cerebral calcification - narrow panel v0.4 Ellen McDonagh Changed child panels to:
Panel types changed to GMS Rare Disease Virtual
White matter disorders and cerebral calcification - narrow panel v0.2 Ellen McDonagh Panel status changed from public to internal
White matter disorders and cerebral calcification - narrow panel v0.1 Ellen McDonagh Panel types changed to GMS Rare Disease Virtual; Super Panel
Genetic epilepsy syndromes v0.851 FH Louise Daugherty Marked gene: FH as ready
Genetic epilepsy syndromes v0.851 FH Louise Daugherty Gene: fh has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.851 FH Louise Daugherty Classified gene: FH as Green List (high evidence)
Genetic epilepsy syndromes v0.851 FH Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green. Appropriate phenotype, sufficient cases, and external review comment all support gene-disease association.
Genetic epilepsy syndromes v0.851 FH Louise Daugherty Gene: fh has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.850 FH Louise Daugherty Publications for gene: FH were set to 2314594; 10805328; 10805328; 20301679
Genetic epilepsy syndromes v0.849 HCFC1 Ivone Leong Mode of inheritance for gene: HCFC1 was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Genetic epilepsy syndromes v0.848 HCFC1 Ivone Leong Phenotypes for gene: HCFC1 were changed from Mental retardation, X-linked 3 (methylmalonic acidemia and homocysteinemia, cblX type ), 309541 to Mental retardation, X-linked 3 (methylmalonic acidemia and homocysteinemia, cblX type), 309541
Genetic epilepsy syndromes v0.847 FH Louise Daugherty edited their review of gene: FH: Added comment: From GeneReview PMID: 20301679. Fumarate hydratase deficiency results in severe neonatal and early infantile encephalopathy that is characterized by poor feeding, failure to thrive, hypotonia, lethargy, and seizures. Epileptic seizures are common (40%-80%), although age of onset and seizure type are variable (PMID:10805328, PMID:20549362). Infantile spasms (epileptic spasms) accompanied by hypsarrhythmia on EEG have been reported (PMID:15221078, PMID:16151915).; Changed rating: GREEN
Genetic epilepsy syndromes v0.847 HCFC1 Ivone Leong Phenotypes for gene: HCFC1 were changed from Mental retardation, X-linked 3 (methylmalonic acidemia and homocysteinemia, cblX type ) to Mental retardation, X-linked 3 (methylmalonic acidemia and homocysteinemia, cblX type ), 309541
Genetic epilepsy syndromes v0.846 HCFC1 Ivone Leong Phenotypes for gene: HCFC1 were changed from to Mental retardation, X-linked 3 (methylmalonic acidemia and homocysteinemia, cblX type )
Genetic epilepsy syndromes v0.845 FH Louise Daugherty Added comment: Comment on publications: Added publications to support upgrading of the gene to Green
Genetic epilepsy syndromes v0.845 FH Louise Daugherty Publications for gene: FH were set to
Genetic epilepsy syndromes v0.844 FH Louise Daugherty Added comment: Comment on mode of inheritance: Added MOI from external clinical review and publications
Genetic epilepsy syndromes v0.844 FH Louise Daugherty Mode of inheritance for gene: FH was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.843 FH Louise Daugherty Added comment: Comment on phenotypes: Added phenotype suggested from expert review that indicate relevance to inclusion on the Genetic Epilepsy Syndromes panel.
Genetic epilepsy syndromes v0.843 FH Louise Daugherty Phenotypes for gene: FH were changed from to Fumarase deficiency, 606812; Seizures
Genetic epilepsy syndromes v0.842 NSDHL Eleanor Williams Marked gene: NSDHL as ready
Genetic epilepsy syndromes v0.842 NSDHL Eleanor Williams Added comment: Comment when marking as ready: 3 cases/variants in unrelated families where male show seizures. One SNV is missense but it segregates with the disease in the family, is predicted to affect protein function and is not found in dbSNP.
Genetic epilepsy syndromes v0.842 NSDHL Eleanor Williams Gene: nsdhl has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.842 NSDHL Eleanor Williams Phenotypes for gene: NSDHL were changed from to CK syndrome 300831
Genetic epilepsy syndromes v0.841 NSDHL Eleanor Williams Mode of inheritance for gene: NSDHL was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Genetic epilepsy syndromes v0.840 NSDHL Eleanor Williams Publications for gene: NSDHL were set to
Genetic epilepsy syndromes v0.839 NSDHL Eleanor Williams Classified gene: NSDHL as Green List (high evidence)
Genetic epilepsy syndromes v0.839 NSDHL Eleanor Williams Added comment: Comment on list classification: 3 cases reported of variants in this gene in males with CK syndrome.
Genetic epilepsy syndromes v0.839 NSDHL Eleanor Williams Gene: nsdhl has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.838 NSDHL Eleanor Williams commented on gene: NSDHL
Genetic epilepsy syndromes v0.838 FGFR3 Louise Daugherty Publications for gene: FGFR3 were set to 27485793; 23649205; 24630288; 17621485; 16222682; 12794698; 23044018; 12794698; 18000976; http://doi.org/10.15844/pedneurbriefs-26-12-6; http://www.ashg.org/genetics/ashg07s/f20570.htm
Genetic epilepsy syndromes v0.837 FGFR3 Louise Daugherty Publications for gene: FGFR3 were set to 27485793; 23649205; 24630288; 17621485; 16222682; 12794698; 23044018; 12794698; 18000976; http://doi.org/10.15844/pedneurbriefs-26-12-6
Genetic epilepsy syndromes v0.836 FGFR3 Louise Daugherty Phenotypes for gene: FGFR3 were changed from Hypochondroplasia, 146000; Focal Epilepsy; Muenke syndrome 602849, Epilepsy to Hypochondroplasia, 146000; Focal Epilepsy; Muenke syndrome, 602849; Epilepsy
Genetic epilepsy syndromes v0.835 FGFR3 Louise Daugherty Marked gene: FGFR3 as ready
Genetic epilepsy syndromes v0.835 FGFR3 Louise Daugherty Gene: fgfr3 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.835 FGFR3 Louise Daugherty Classified gene: FGFR3 as Green List (high evidence)
Genetic epilepsy syndromes v0.835 FGFR3 Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green. Appropriate phenotypes, sufficient cases, and external review comment all support gene-disease association.
Genetic epilepsy syndromes v0.835 FGFR3 Louise Daugherty Gene: fgfr3 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.834 FGFR3 Louise Daugherty edited their review of gene: FGFR3: Changed rating: GREEN
Genetic epilepsy syndromes v0.834 FGFR3 Louise Daugherty Publications for gene: FGFR3 were set to 27485793; 23649205; 24630288; 17621485; 16222682; 12794698; 23044018; 12794698; 18000976
Genetic epilepsy syndromes v0.833 FGFR3 Louise Daugherty Added comment: Comment on phenotypes: added additional relevant phenotype Muenke syndrome Millichap, J.G., 2012. Epilepsy in Muenke Syndrome. Pediatric Neurology Briefs, 26(12), pp.93–93. DOI: http://doi.org/10.15844/pedneurbriefs-26-12-6 : A review of 789 published cases of Muenke syndrome with neurological complications identified epilepsy in 6 cases, with intracranial anomalies in 5. The intracranial anomalies were agenesis of the corpus callosum, hemimegalencephaly, and porencephaly. In the review of 58 patients with Muenke syndrome in the Washington, DC cohort, 7 (12%) had epilepsy and 4 survived neonatal apnea. Patients with Muenke syndrome should be monitored for apnea and seizures.
Genetic epilepsy syndromes v0.833 FGFR3 Louise Daugherty Phenotypes for gene: FGFR3 were changed from Hypochondroplasia, 146000; Focal epilepsy to Hypochondroplasia, 146000; Focal Epilepsy; Muenke syndrome 602849, Epilepsy
Genetic epilepsy syndromes v0.832 FGFR3 Louise Daugherty Mode of inheritance for gene: FGFR3 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic epilepsy syndromes v0.831 FGFR3 Louise Daugherty Added comment: Comment on publications: Hypochondroplasia and FGFR3 variants are associated with characteristic abnormalities involving bilaterally medial temporal lobe structures, probable hippocampal cortex focal dysplasia, and early onset of focal epilepsy and was first reported PMID: 24630288 (2014). Subsequent cases PMID: 27485793, PMID:23649205, PMID:12794698. In addition, patients with with Muenke syndrome (MS) also show similarities in early-onset temporal lobe-related seizures PMID:23044018, PMID:12794698, PMID:18000976.
Genetic epilepsy syndromes v0.831 FGFR3 Louise Daugherty Publications for gene: FGFR3 were set to
Genetic epilepsy syndromes v0.830 FGFR3 Louise Daugherty Added comment: Comment on phenotypes: Added phenotype suggested from expert review that indicate relevance to inclusion on the Genetic Epilepsy Syndromes panel.
Genetic epilepsy syndromes v0.830 FGFR3 Louise Daugherty Phenotypes for gene: FGFR3 were changed from to Hypochondroplasia, 146000; Focal epilepsy
Genetic epilepsy syndromes v0.829 HCCS Ivone Leong Mode of inheritance for gene: HCCS was changed from to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Genetic epilepsy syndromes v0.828 FBXL4 Louise Daugherty Phenotypes for gene: FBXL4 were changed from Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type), 615471 to Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type), 615471; Seizures
Genetic epilepsy syndromes v0.827 HCCS Ivone Leong Phenotypes for gene: HCCS were changed from to Linear skin defects with multiple congenital anomalies 1, 309801
Polycystic liver disease v0.34 DGUOK Ivone Leong Publications for gene: DGUOK were set to
Polycystic liver disease v0.33 DGUOK Ivone Leong Classified gene: DGUOK as Green List (high evidence)
Polycystic liver disease v0.33 DGUOK Ivone Leong Added comment: Comment on list classification: Promoted from amber to green. DGUOK is a green gene on the 'Undiagnosed metabolic disorders' and 'Mitochondrial disorders' panels.

Dr Bill Griffiths (Addenbrooke's Hospital, Cambridge, UK) suggested: DGUOK based on OMIM 617068 and the description and reference within that entry.

In one study (30234759) showed 2 unrelated families with 3 affected members (all by consanguineous parents) have portal hypertension. The DGUOK variant is a missense mutation. No functional studies were performed.
In a second study (17073823) a proband showed liver fibrosis and compound missense mutations in DGUOK (one of which was the same missense mutation found in 30234759). In vitro studies were performed using fibroblasts taken from patient, which showed that the variant caused reduced enzyme activity.
Polycystic liver disease v0.33 DGUOK Ivone Leong Gene: dguok has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.826 FGF12 Louise Daugherty Marked gene: FGF12 as ready
Genetic epilepsy syndromes v0.826 FGF12 Louise Daugherty Gene: fgf12 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.826 FGF12 Louise Daugherty Classified gene: FGF12 as Green List (high evidence)
Genetic epilepsy syndromes v0.826 FGF12 Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green. Appropriate phenotype, sufficient cases, and external review comment all support gene-disease association.
Genetic epilepsy syndromes v0.826 FGF12 Louise Daugherty Gene: fgf12 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.825 FGF12 Louise Daugherty Added comment: Comment on mode of inheritance: changed MOI from external clinical review and publications
Genetic epilepsy syndromes v0.825 FGF12 Louise Daugherty Mode of inheritance for gene: FGF12 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic epilepsy syndromes v0.824 FGF12 Louise Daugherty Added comment: Comment on publications: Added publications that support the association with the phenotype suggested by external reviewer and recent publication PMID:29699863 that describes two unrelated cases, 1 Japanese patient diagnosed with early infantile epileptic encephalopathy (EIEE) and another diagnosed with epilepsy of infancy with migrating focal seizures (EIMFS). Both patients had an identical heterozygous missense mutation [c.341G>A:p.(Arg114His)] in FGF12 , which was identified with whole-exome sequencing. The mutation is identical to previously reported mutations in cases with early onset epileptic encephalopathy.
Genetic epilepsy syndromes v0.824 FGF12 Louise Daugherty Publications for gene: FGF12 were set to
Dilated cardiomyopathy - teen and adult v1.34 PPP1R13L Sian Ellard reviewed gene: PPP1R13L: Rating: GREEN; Mode of pathogenicity: None; Publications: 28864777, 15661756; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Genetic epilepsy syndromes v0.823 FBXL4 Louise Daugherty Marked gene: FBXL4 as ready
Genetic epilepsy syndromes v0.823 FBXL4 Louise Daugherty Gene: fbxl4 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.823 FBXL4 Louise Daugherty Classified gene: FBXL4 as Green List (high evidence)
Genetic epilepsy syndromes v0.823 FBXL4 Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green. Enough evidence to support gene-disease association and relevance to this panel to rate this gene Green
Genetic epilepsy syndromes v0.823 FBXL4 Louise Daugherty Gene: fbxl4 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.822 FBXL4 Louise Daugherty Publications for gene: FBXL4 were set to 23993193; 23993194; 25868664; 26404457; 27182039; 27290639; 27099744; 27743463
Genetic epilepsy syndromes v0.821 FBXL4 Louise Daugherty edited their review of gene: FBXL4: Added comment: FBXL4 defects are common in patients with congenital lactic acidemia and encephalomyopathic mitochondrial DNA depletion syndrome, seizures are part of the clinical phenotype and can start at age four months (Dai et al 2017 PMID: 27743463). Seizure types reported include complex partial seizures (Baroy et al 2016 PMID:27182039) and absence and generalized seizures (Gai et al 2013 PMID:23993194). The clinical manifestations of FBXL4-Related mtDNA Depletion Syndrome with seizures occurs at a frequency of approximately 33% of cases (Almannai et al 2017 PMID:28383868); Changed rating: GREEN
Genetic epilepsy syndromes v0.821 FBXL4 Louise Daugherty Added comment: Comment on publications: FBXL4-related mtDNA depletion syndrome has been reported in 50 individuals to date. Added publications suggested to support upgrading of the gene to Green.
Genetic epilepsy syndromes v0.821 FBXL4 Louise Daugherty Publications for gene: FBXL4 were set to
Genetic epilepsy syndromes v0.820 FGF12 Louise Daugherty Added comment: Comment on phenotypes: added phenotype from external review and checked with OMIM
Genetic epilepsy syndromes v0.820 FGF12 Louise Daugherty Phenotypes for gene: FGF12 were changed from to Epileptic encephalopathy, early infantile, 47, 617166
Genetic epilepsy syndromes v0.819 GPHN Ivone Leong Mode of inheritance for gene: GPHN was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.818 GPHN Ivone Leong Phenotypes for gene: GPHN were changed from to Molybdenum cofactor deficiency C, 615501
Genetic epilepsy syndromes v0.817 GTPBP3 Ivone Leong Publications for gene: GTPBP3 were set to
Genetic epilepsy syndromes v0.816 GTPBP3 Ivone Leong Mode of inheritance for gene: GTPBP3 was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.815 FBXL4 Louise Daugherty Added comment: Comment on phenotypes: added OMIM phenotype and MIMid
Genetic epilepsy syndromes v0.815 FBXL4 Louise Daugherty Phenotypes for gene: FBXL4 were changed from to Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type), 615471
Genetic epilepsy syndromes v0.814 GTPBP3 Ivone Leong Phenotypes for gene: GTPBP3 were changed from to Combined oxidative phosphorylation deficiency 23, 616198
Genetic epilepsy syndromes v0.813 FBXL4 Louise Daugherty Added comment: Comment on mode of inheritance: Added MOI from external review and checked with PMID
Genetic epilepsy syndromes v0.813 FBXL4 Louise Daugherty Mode of inheritance for gene: FBXL4 was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.812 GTPBP3 Ivone Leong Marked gene: GTPBP3 as ready
Genetic epilepsy syndromes v0.812 GTPBP3 Ivone Leong Added comment: Comment when marking as ready: Associated with 'mitochondrial translation defect associated with hypertrophic cardiomyopathy, lactic acidosis, and encephalopathy' in Gene2phenotype. Only 2 unrelated families have been reported to have seizures.
Genetic epilepsy syndromes v0.812 GTPBP3 Ivone Leong Gene: gtpbp3 has been classified as Amber List (Moderate Evidence).
Intellectual disability v2.532 FBXL4 Louise Daugherty Added comment: Comment on phenotypes: added OMIM phenotype and MIMid
Intellectual disability v2.532 FBXL4 Louise Daugherty Phenotypes for gene: FBXL4 were changed from FATAL ENCEPHALOPATHY, LACTIC ACIDOSIS, AND SEVERE MTDNA DEPLETION IN MUSCLE to Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type), 615471; FATAL ENCEPHALOPATHY, LACTIC ACIDOSIS, AND SEVERE MTDNA DEPLETION IN MUSCLE
Genetic epilepsy syndromes v0.812 TIMM50 Rebecca Foulger commented on gene: TIMM50: Added 'watchlist' tag.
Genetic epilepsy syndromes v0.812 TIMM50 Rebecca Foulger Tag watchlist tag was added to gene: TIMM50.
Genetic epilepsy syndromes v0.812 SUCLG1 Rebecca Foulger commented on gene: SUCLG1: Added 'watchlist' tag.
Genetic epilepsy syndromes v0.812 SUCLG1 Rebecca Foulger Tag watchlist tag was added to gene: SUCLG1.
Genetic epilepsy syndromes v0.812 SUCLG1 Rebecca Foulger commented on gene: SUCLG1: PMID:26475597 (Carrozzo et al 2016) report 25 new patients with succinate-CoA ligase deficiency, and review the clinical and molecular findings in these and 46 previously reported patients. Of the 71 patients, 50 had SUCLA2 mutations and 21 had SUCLG1 mutations. Epilepsy was much more frequent in patients with SUCLA2 mutations compared to patients with SUCLG1 mutations: Only 1 patient with the SUCLG1 variant had epilepsy.
Genetic epilepsy syndromes v0.812 SUCLA2 Rebecca Foulger Marked gene: SUCLA2 as ready
Genetic epilepsy syndromes v0.812 SUCLA2 Rebecca Foulger Gene: sucla2 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.812 SUCLA2 Rebecca Foulger Classified gene: SUCLA2 as Green List (high evidence)
Genetic epilepsy syndromes v0.812 SUCLA2 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green. Green review plus sufficient cases (>3) of seizures in MMA patients (At least 3 new patients in PMID:26475597, 2 cousins from 1 family in PMID:15877282, and 1 Faroe Island patient in PMID:17287286/17301081).
Genetic epilepsy syndromes v0.812 SUCLA2 Rebecca Foulger Gene: sucla2 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.811 SUCLA2 Rebecca Foulger commented on gene: SUCLA2: PMID:26475597 (Carrozzo et al 2016) report 25 new patients with succinate-CoA ligase deficiency, and review the clinical and molecular findings in these and 46 previously reported patients. Of the 71 patients, 50 had SUCLA2 mutations and 21 had SUCLG1 mutations. Epilepsy reported as generalized seizures, unspecified epilesy or infantile spasms was mainly reported in patients with SUCLA2 variants. Only 1 patient with the SUCLG1 variant had epilepsy (5%). At least 3 cases of epilepsy listed in new patients with SUCLA2 variants (supplementary material).
Genetic epilepsy syndromes v0.811 SUCLA2 Rebecca Foulger Publications for gene: SUCLA2 were set to 17301081; 17287286; 15877282; 23759946
Genetic epilepsy syndromes v0.810 COQ9 Sarah Leigh Marked gene: COQ9 as ready
Genetic epilepsy syndromes v0.810 COQ9 Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene for Coenzyme Q10 deficiency, primary, 5, 614654, although seizures are not mentioned. At least 2 loss of function variants have been reported in two unrelated cases. In vitro studies show that expression of wildtype COQ9 in patient cells carrying homozygous c.521+1del can rescue reduced activity of mitochondrial complex II/III and restore CoQ10 and COQ7 levels (PMID 26081641)
Genetic epilepsy syndromes v0.810 COQ9 Sarah Leigh Gene: coq9 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.810 COQ9 Sarah Leigh Publications for gene: COQ9 were set to
Genetic epilepsy syndromes v0.809 COQ9 Sarah Leigh Classified gene: COQ9 as Green List (high evidence)
Genetic epilepsy syndromes v0.809 COQ9 Sarah Leigh Gene: coq9 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.808 COQ9 Sarah Leigh Mode of inheritance for gene: COQ9 was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.807 COQ9 Sarah Leigh Phenotypes for gene: COQ9 were changed from to Coenzyme Q10 deficiency, primary, 5, 614654
Genetic epilepsy syndromes v0.806 COQ6 Sarah Leigh Marked gene: COQ6 as ready
Genetic epilepsy syndromes v0.806 COQ6 Sarah Leigh Gene: coq6 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v0.806 COQ6 Sarah Leigh Mode of inheritance for gene: COQ6 was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.805 COQ6 Sarah Leigh Phenotypes for gene: COQ6 were changed from to Coenzyme Q10 deficiency, primary, 6, 614650
Genetic epilepsy syndromes v0.804 COQ4 Sarah Leigh Marked gene: COQ4 as ready
Genetic epilepsy syndromes v0.804 COQ4 Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 6 variants reported in unrelated cases in which seizures are a phenotypic feature.
Genetic epilepsy syndromes v0.804 COQ4 Sarah Leigh Gene: coq4 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.804 COQ4 Sarah Leigh Classified gene: COQ4 as Green List (high evidence)
Genetic epilepsy syndromes v0.804 COQ4 Sarah Leigh Gene: coq4 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.803 COQ4 Sarah Leigh Phenotypes for gene: COQ4 were changed from to Coenzyme Q10 deficiency, primary, 7 616276
Genetic epilepsy syndromes v0.802 COQ4 Sarah Leigh Publications for gene: COQ4 were set to
Genetic epilepsy syndromes v0.801 COQ4 Sarah Leigh Mode of inheritance for gene: COQ4 was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.800 COQ2 Sarah Leigh Marked gene: COQ2 as ready
Genetic epilepsy syndromes v0.800 COQ2 Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 3 variants reported in unrelated cases in which seizures are a phenotypic feature.
Genetic epilepsy syndromes v0.800 COQ2 Sarah Leigh Gene: coq2 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.800 COQ2 Sarah Leigh Classified gene: COQ2 as Green List (high evidence)
Genetic epilepsy syndromes v0.800 COQ2 Sarah Leigh Gene: coq2 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.799 COQ2 Sarah Leigh Publications for gene: COQ2 were set to
Genetic epilepsy syndromes v0.798 SUCLA2 Rebecca Foulger Publications for gene: SUCLA2 were set to
Genetic epilepsy syndromes v0.797 SUCLA2 Rebecca Foulger commented on gene: SUCLA2: Jaberi et al 2013 (PMID:23759946) identified a homozygous c.751G>A transition in SUCLA2 (D251N) in 2 Iranian cousins with MIM:612073. No sign of epilepsy was seen in Patient 1. Epilepsy was not mentioned for the cousin (Patient 2).
Genetic epilepsy syndromes v0.797 SUCLA2 Rebecca Foulger commented on gene: SUCLA2: Elpeleg et al 2005 (PMID:15877282) identified a homozgyous deletion/insertion in SUCLA2 in 2 first cousins from a consanguineous Muslim family. Both cousins had generalized seizures from age 1 and age 3.
Genetic epilepsy syndromes v0.797 SUCLA2 Rebecca Foulger commented on gene: SUCLA2
Genetic epilepsy syndromes v0.797 COQ2 Sarah Leigh Phenotypes for gene: COQ2 were changed from to Coenzyme Q10 deficiency, primary, 1 607426
Genetic epilepsy syndromes v0.796 COQ2 Sarah Leigh Mode of inheritance for gene: COQ2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.795 COL4A2 Sarah Leigh Marked gene: COL4A2 as ready
Genetic epilepsy syndromes v0.795 COL4A2 Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as both DD and IF Gen2Phen gene. At least 3 variants reported in unrelated cases in which seizures are a phenotypic feature.
Genetic epilepsy syndromes v0.795 COL4A2 Sarah Leigh Gene: col4a2 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.795 COL4A2 Sarah Leigh Classified gene: COL4A2 as Green List (high evidence)
Genetic epilepsy syndromes v0.795 COL4A2 Sarah Leigh Gene: col4a2 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.794 COL4A2 Sarah Leigh Publications for gene: COL4A2 were set to
Genetic epilepsy syndromes v0.793 COL4A2 Sarah Leigh Phenotypes for gene: COL4A2 were changed from to Porencephaly 2 614483
Genetic epilepsy syndromes v0.792 COL4A2 Sarah Leigh Mode of inheritance for gene: COL4A2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic epilepsy syndromes v0.791 SUCLA2 Rebecca Foulger Mode of inheritance for gene: SUCLA2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.790 SUCLA2 Rebecca Foulger Phenotypes for gene: SUCLA2 were changed from to Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), 612073
Genetic epilepsy syndromes v0.789 SUCLG1 Rebecca Foulger Marked gene: SUCLG1 as ready
Genetic epilepsy syndromes v0.789 SUCLG1 Rebecca Foulger Added comment: Comment when marking as ready: Marked as Ready: November 13th 2018.
Genetic epilepsy syndromes v0.789 SUCLG1 Rebecca Foulger Gene: suclg1 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v0.789 COL4A1 Sarah Leigh Marked gene: COL4A1 as ready
Genetic epilepsy syndromes v0.789 COL4A1 Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 4 variants reported in unrelated cases in which seizures are a phenotypic feature.
Genetic epilepsy syndromes v0.789 COL4A1 Sarah Leigh Gene: col4a1 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.789 SUCLG1 Rebecca Foulger commented on gene: SUCLG1: PMID:22231385 (Honzik et al 2012) report 1 patient with SUCLG1 variant, who did not have seizures.
Genetic epilepsy syndromes v0.789 SUCLG1 Rebecca Foulger Classified gene: SUCLG1 as Amber List (moderate evidence)
Genetic epilepsy syndromes v0.789 SUCLG1 Rebecca Foulger Added comment: Comment on list classification: Kept rating as Amber. Confirmed DD-G2P gene for FATAL INFANTILE LACTIC ACIDOSIS. Although patients with SUCLG1 variants can report with seizures (1 of 3 patients in PMID:26028457 plus EEG abnormalities in PMID:27484306), there are currently insufficient cases to rate as diagnostic.
Genetic epilepsy syndromes v0.789 SUCLG1 Rebecca Foulger Gene: suclg1 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v0.788 COL4A1 Sarah Leigh Classified gene: COL4A1 as Green List (high evidence)
Genetic epilepsy syndromes v0.788 COL4A1 Sarah Leigh Gene: col4a1 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.787 SUCLG1 Rebecca Foulger commented on gene: SUCLG1: PMID:28358460 gives an overview of treatment of seizures when present in SUCLG1-related mitochondrial DNA (mtDNA) depletion syndrome patients.
Genetic epilepsy syndromes v0.787 SUCLG1 Rebecca Foulger commented on gene: SUCLG1: Seizures are not reported in the clinical phenotype of patients in PMIDs 17668387, 19526370 and 20693550, which report patients with SUCLG1 variants.
Genetic epilepsy syndromes v0.787 SUCLG1 Rebecca Foulger Added comment: Comment on publications: PMID:27143079 article is in Chinese. See PMID:26028457 for a description of the same patients.
Genetic epilepsy syndromes v0.787 SUCLG1 Rebecca Foulger Publications for gene: SUCLG1 were set to 28358460; 27143079; 26028457; 27484306
Genetic epilepsy syndromes v0.786 COL4A1 Sarah Leigh Publications for gene: COL4A1 were set to
Genetic epilepsy syndromes v0.785 COL4A1 Sarah Leigh Phenotypes for gene: COL4A1 were changed from to Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps 611773; Brain small vessel disease with or without ocular anomalies 607595; Porencephaly 1 175780; Schizencephaly 269160
Genetic epilepsy syndromes v0.784 SUCLG1 Rebecca Foulger commented on gene: SUCLG1: PMID:26028457 (Liu et al 2016) report 3 unrelated Chinese patients with severe psychomotor retardation, hypotonia, dystonia and athetoid movements, and homozygous/compound het variants in SUCLG1. Patient 2 had Epilepsy (Table 1).
Genetic epilepsy syndromes v0.784 SUCLG1 Rebecca Foulger commented on gene: SUCLG1
Genetic epilepsy syndromes v0.784 SUCLG1 Rebecca Foulger Publications for gene: SUCLG1 were set to
Genetic epilepsy syndromes v0.783 COL4A1 Sarah Leigh Mode of inheritance for gene: COL4A1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic epilepsy syndromes v0.782 COL18A1 Sarah Leigh Marked gene: COL18A1 as ready
Genetic epilepsy syndromes v0.782 COL18A1 Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 4 truncating variants reported in 3 unrelated cases in which seizures are a phenotypic feature.
Genetic epilepsy syndromes v0.782 COL18A1 Sarah Leigh Gene: col18a1 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.782 COL18A1 Sarah Leigh Classified gene: COL18A1 as Green List (high evidence)
Genetic epilepsy syndromes v0.782 COL18A1 Sarah Leigh Gene: col18a1 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.781 COL18A1 Sarah Leigh Publications for gene: COL18A1 were set to
Genetic epilepsy syndromes v0.780 SUCLG1 Rebecca Foulger Mode of inheritance for gene: SUCLG1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.779 SUCLG1 Rebecca Foulger Phenotypes for gene: SUCLG1 were changed from to Mitochondrial DNA depletion syndrome 9 (encephalomyopathic type with methylmalonic aciduria), 245400
Genetic epilepsy syndromes v0.778 COL18A1 Sarah Leigh Phenotypes for gene: COL18A1 were changed from to Knobloch syndrome, type 1 267750
Genetic epilepsy syndromes v0.777 COL18A1 Sarah Leigh Mode of inheritance for gene: COL18A1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.776 CLN3 Sarah Leigh Marked gene: CLN3 as ready
Genetic epilepsy syndromes v0.776 CLN3 Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 3 variants reported in 3 unrelated cases in which seizures are a phenotypic feature.
Genetic epilepsy syndromes v0.776 CLN3 Sarah Leigh Gene: cln3 has been classified as Green List (High Evidence).
Polycystic liver disease v0.32 RPGRIP1L Ivone Leong Publications for gene: RPGRIP1L were set to
Genetic epilepsy syndromes v0.776 CLN3 Sarah Leigh Classified gene: CLN3 as Green List (high evidence)
Genetic epilepsy syndromes v0.776 CLN3 Sarah Leigh Gene: cln3 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.775 CLN3 Sarah Leigh Publications for gene: CLN3 were set to
Polycystic liver disease v0.31 RPGRIP1L Ivone Leong Classified gene: RPGRIP1L as Green List (high evidence)
Polycystic liver disease v0.31 RPGRIP1L Ivone Leong Added comment: Comment on list classification: RPGRIP1L is a green gene on the Rare multisystem ciliopathy disorder panel (https://panelapp.genomicsengland.co.uk/panels/150/). It has been promoted from grey to green as it causes both Meckel syndrome (611561) and COACH syndrome (216360), which is considered by some to be a subtype of Joubert syndrome with congenital hepatic fibrosis.
Polycystic liver disease v0.31 RPGRIP1L Ivone Leong Gene: rpgrip1l has been classified as Green List (High Evidence).
Polycystic liver disease v0.30 CC2D2A Ivone Leong Publications for gene: CC2D2A were set to
Polycystic liver disease v0.29 CC2D2A Ivone Leong Classified gene: CC2D2A as Green List (high evidence)
Polycystic liver disease v0.29 CC2D2A Ivone Leong Added comment: Comment on list classification: CC2D2A is a green gene on the Rare multisystem ciliopathy disorder panel (https://panelapp.genomicsengland.co.uk/panels/150/). It has been promoted from grey to green as it causes COACH syndrome (216360), which is considered by some to be a subtype of Joubert syndrome with congenital hepatic fibrosis.
Polycystic liver disease v0.29 CC2D2A Ivone Leong Gene: cc2d2a has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.774 CLN3 Sarah Leigh Phenotypes for gene: CLN3 were changed from to Ceroid lipofuscinosis, neuronal, 3 204200
Genetic epilepsy syndromes v0.773 CLN3 Sarah Leigh Mode of inheritance for gene: CLN3 was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.772 CLCN4 Sarah Leigh Marked gene: CLCN4 as ready
Genetic epilepsy syndromes v0.772 CLCN4 Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as possible Gen2Phen gene for INFANTILE EPILEPTIC ENCEPHALOPATHY AND/OR INTELLECTUAL DISABILITY. At least 2 variants reported in 3 unrelated cases in whom seizures are included in their phenotypic features. Supportive functional studies are also reported (PMID 27550844).
Genetic epilepsy syndromes v0.772 CLCN4 Sarah Leigh Gene: clcn4 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.772 CLCN4 Sarah Leigh Mode of inheritance for gene: CLCN4 was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Genetic epilepsy syndromes v0.771 CLCN4 Sarah Leigh Publications for gene: CLCN4 were set to
Genetic epilepsy syndromes v0.770 CLCN4 Sarah Leigh Phenotypes for gene: CLCN4 were changed from to Raynaud-Claes syndrome 300114; Mental retardation, X-linked 49/15
Genetic epilepsy syndromes v0.769 CLCN4 Sarah Leigh Classified gene: CLCN4 as Green List (high evidence)
Genetic epilepsy syndromes v0.769 CLCN4 Sarah Leigh Gene: clcn4 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.768 STRADA Sarah Leigh edited their review of gene: STRADA: Changed rating: GREEN
Genetic epilepsy syndromes v0.768 CACNA1G Sarah Leigh edited their review of gene: CACNA1G: Changed rating: GREEN
Genetic epilepsy syndromes v0.768 CCDC88A Sarah Leigh Marked gene: CCDC88A as ready
Genetic epilepsy syndromes v0.768 CCDC88A Sarah Leigh Added comment: Comment when marking as ready: Insufficient evidence at present for gene to be green (13/11/2018)
Genetic epilepsy syndromes v0.768 CCDC88A Sarah Leigh Gene: ccdc88a has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v0.768 CCDC88A Sarah Leigh Tag watchlist tag was added to gene: CCDC88A.
Genetic epilepsy syndromes v0.768 CCDC88A Sarah Leigh Phenotypes for gene: CCDC88A were changed from to ?PEHO syndrome-like 617507
Genetic epilepsy syndromes v0.767 CCDC88A Sarah Leigh Publications for gene: CCDC88A were set to
Genetic epilepsy syndromes v0.766 CCDC88A Sarah Leigh Mode of inheritance for gene: CCDC88A was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.765 CCDC88A Sarah Leigh Mode of inheritance for gene: CCDC88A was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.764 ADAT3 Sarah Leigh Marked gene: ADAT3 as ready
Genetic epilepsy syndromes v0.764 ADAT3 Sarah Leigh Gene: adat3 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v0.764 ADAT3 Sarah Leigh Phenotypes for gene: ADAT3 were changed from # 615286. MENTAL RETARDATION, AUTOSOMAL RECESSIVE 36; MRT36 to Mental retardation, autosomal recessive 36 615286
Polycystic liver disease v0.28 TMEM67 Ivone Leong commented on gene: TMEM67: TMEM67 also causes COACH syndrome (609884), which is considered by some to be a subtype of Joubert syndrome with congenital hepatic fibrosis.
Genetic epilepsy syndromes v0.763 CASK Sarah Leigh Marked gene: CASK as ready
Genetic epilepsy syndromes v0.763 CASK Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 5 variants reported in unrelated cases with seizures included in their phenotype.
Genetic epilepsy syndromes v0.763 CASK Sarah Leigh Gene: cask has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.763 CASK Sarah Leigh Classified gene: CASK as Green List (high evidence)
Genetic epilepsy syndromes v0.763 CASK Sarah Leigh Gene: cask has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.762 CASK Sarah Leigh Publications for gene: CASK were set to
Genetic epilepsy syndromes v0.761 CASK Sarah Leigh Mode of inheritance for gene: CASK was changed from to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Genetic epilepsy syndromes v0.760 CASK Sarah Leigh Phenotypes for gene: CASK were changed from to Mental retardation and microcephaly with pontine and cerebellar hypoplasia 300749; Mental retardation, with or without nystagmus 300422
Genetic epilepsy syndromes v0.759 CACNA2D2 Sarah Leigh Tag watchlist tag was added to gene: CACNA2D2.
Genetic epilepsy syndromes v0.759 CACNA2D2 Sarah Leigh Marked gene: CACNA2D2 as ready
Genetic epilepsy syndromes v0.759 CACNA2D2 Sarah Leigh Added comment: Comment when marking as ready: Not associated with phenotype in OMIM or in Gen2Phen. Both variant reported have been refuted in OMIM and are now listed as VUS, however, the mouse model reported in PMID 11487633 does provide some evidence for involvement of this gene in epilepsy.
Genetic epilepsy syndromes v0.759 CACNA2D2 Sarah Leigh Gene: cacna2d2 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v0.759 CACNA2D2 Sarah Leigh Publications for gene: CACNA2D2 were set to 24358150; 23339110; 11487633
Genetic epilepsy syndromes v0.758 CACNA2D2 Sarah Leigh Phenotypes for gene: CACNA2D2 were changed from to Absence epilepsy
Genetic epilepsy syndromes v0.757 CACNA2D2 Sarah Leigh Publications for gene: CACNA2D2 were set to
Genetic epilepsy syndromes v0.756 CACNA2D2 Sarah Leigh Mode of inheritance for gene: CACNA2D2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.755 C12orf57 Sarah Leigh Marked gene: C12orf57 as ready
Genetic epilepsy syndromes v0.755 C12orf57 Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 7 variants reported in a total of 56 cases of which 41 had seizures as a phenotypic feature.
Genetic epilepsy syndromes v0.755 C12orf57 Sarah Leigh Gene: c12orf57 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.755 C12orf57 Sarah Leigh Classified gene: C12orf57 as Green List (high evidence)
Genetic epilepsy syndromes v0.755 C12orf57 Sarah Leigh Gene: c12orf57 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.754 C12orf57 Sarah Leigh Publications for gene: C12orf57 were set to 23453666, 24798461, 23633300, 23453665
Genetic epilepsy syndromes v0.753 C12orf57 Sarah Leigh Phenotypes for gene: C12orf57 were changed from to Temtamy syndrome 218340
Genetic epilepsy syndromes v0.752 C12orf57 Sarah Leigh Publications for gene: C12orf57 were set to
Genetic epilepsy syndromes v0.751 C12orf57 Sarah Leigh Mode of inheritance for gene: C12orf57 was changed from to BIALLELIC, autosomal or pseudoautosomal
Inherited bleeding disorders v1.145 GBA Louise Daugherty commented on gene: GBA: Update from NIHRRD-BR BRIDGE they will no longer be reporting on this gene on their platform. After discussion with Genomics England Clinical team, as the MOI is listed as biallelic so we would only prioritise variants that are homozygous or compound het. A parent might be found to be a carrier, when their child has the condition but that is to be expected and would be useful information. Gaucher is associated with haematological manifestations as part of the wider syndromic phenotype.
Genetic epilepsy syndromes v0.750 BTD Sarah Leigh Marked gene: BTD as ready
Genetic epilepsy syndromes v0.750 BTD Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 4 variants reported 18 cases of Biotinidase deficiency 253260 that include seizures as part of the phenotype.
Genetic epilepsy syndromes v0.750 BTD Sarah Leigh Gene: btd has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.750 BTD Sarah Leigh Classified gene: BTD as Green List (high evidence)
Genetic epilepsy syndromes v0.750 BTD Sarah Leigh Gene: btd has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.749 BTD Sarah Leigh Publications for gene: BTD were set to 24075304; 4073853; 3196050
Genetic epilepsy syndromes v0.748 PET100 Rebecca Foulger Marked gene: PET100 as ready
Genetic epilepsy syndromes v0.748 PET100 Rebecca Foulger Gene: pet100 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.748 PET100 Rebecca Foulger Classified gene: PET100 as Green List (high evidence)
Genetic epilepsy syndromes v0.748 PET100 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green: Green review, and Green rating agreed by Sarah Leigh. Seizures are a recognised phenotype of patients with Mitochondrial complex IV deficiency, which can be caused by variants in multiple genes, including PET100. 2 different PET100 variants reported so far in the literature (including a founder variant in Lebanese patients) in >3 unrelated individuals with seizures as a prominent phenotype (PMIDs24462369 and 23829769).
Genetic epilepsy syndromes v0.748 PET100 Rebecca Foulger Gene: pet100 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.747 BTD Sarah Leigh Added comment: Comment on publications: PMID 24075304 mouse model, with seizures, PMIDs 4073853;3196050, seizures in patients
Genetic epilepsy syndromes v0.747 BTD Sarah Leigh Publications for gene: BTD were set to
Genetic epilepsy syndromes v0.746 BTD Sarah Leigh Mode of inheritance for gene: BTD was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.745 BTD Sarah Leigh Phenotypes for gene: BTD were changed from to Biotinidase deficiency 253260
Genetic epilepsy syndromes v0.744 BRAF Sarah Leigh Marked gene: BRAF as ready
Genetic epilepsy syndromes v0.744 BRAF Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotypes in OMIM and as confirmed Gen2Phen gene for Cardiofaciocutaneous syndrome 115150 & LEOPARD syndrome 3 613707. PMID 18039946 reported seizures in around half of their genetically confirmed Cardiofaciocutaneous syndrome 115150 cases (n=38) and PMID 19206169 reports 11 variants in 9 cases of Cardiofaciocutaneous syndrome 115150, 2 cases of Noonan syndrome 7 613706 and one case of LEOPARD syndrome 3 613707.
Genetic epilepsy syndromes v0.744 BRAF Sarah Leigh Gene: braf has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.744 BRAF Sarah Leigh Classified gene: BRAF as Green List (high evidence)
Genetic epilepsy syndromes v0.744 BRAF Sarah Leigh Gene: braf has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.743 BRAF Sarah Leigh Phenotypes for gene: BRAF were changed from Cardiofaciocutaneous syndrome 115150; LEOPARD syndrome 3 613707 to Cardiofaciocutaneous syndrome 115150; Noonan syndrome 7 613706; LEOPARD syndrome 3 613707
Genetic epilepsy syndromes v0.742 PET100 Rebecca Foulger commented on gene: PET100: Added 'founder effect' tag based on PMID:24462369 who identified a founder variant in patients of Lebanese descent.
Genetic epilepsy syndromes v0.742 PET100 Rebecca Foulger Tag founder-effect tag was added to gene: PET100.
Genetic epilepsy syndromes v0.742 SURF1 Rebecca Foulger Marked gene: SURF1 as ready
Genetic epilepsy syndromes v0.742 SURF1 Rebecca Foulger Gene: surf1 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.742 SURF1 Rebecca Foulger Classified gene: SURF1 as Green List (high evidence)
Genetic epilepsy syndromes v0.742 SURF1 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green. Green review. Confirmed DD-G2P gene for Leigh syndrome and Complex IV deficiency, which can present with seizures. Seizures are a recognised phenotype for Leigh syndrome, although not necessarily in LS patients caused by SURF1 variants (PMID:24462369). However, in their multi-centre study, PMID:24462369 report sufficient cases of SURF1-deficient patients with seizures (6 of 44) for inclusion on this panel.
Genetic epilepsy syndromes v0.742 SURF1 Rebecca Foulger Gene: surf1 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.741 SURF1 Rebecca Foulger commented on gene: SURF1: PMID:28273704 found SURF1 variants in 10 Leigh syndrome patients, making it the most common variation in this study. The most common primary symptoms of patients include seizures. The article is in Chinese so the full article can not be curated at this time.
Genetic epilepsy syndromes v0.741 SURF1 Rebecca Foulger commented on gene: SURF1: Wedatilake et al. 2013 (PMID:23829769) conducted a study of 44 SURF1-deficient patients from 37 pedigrees from 10 different UK centres and two Australian centres. Seizures were found in 14% of patients (6 patients).
Genetic epilepsy syndromes v0.741 SURF1 Rebecca Foulger Added comment: Comment on publications: PMID:24462369 state that seizures aren't a prominent feature of individuals with SURF1 variants.
Genetic epilepsy syndromes v0.741 SURF1 Rebecca Foulger Publications for gene: SURF1 were set to
Genetic epilepsy syndromes v0.740 PET100 Rebecca Foulger commented on gene: PET100: PMID:23829769 report a female patient born to British Pakistani parents with seizures beginning at 48 hours old. She died age 55 hours. She had a pathogenic homozygous nonsense variant in the PET100 gene (c.142C>T, p.Gln48*).
Genetic epilepsy syndromes v0.740 PET100 Rebecca Foulger Publications for gene: PET100 were set to 24462369
Genetic epilepsy syndromes v0.739 BRAF Sarah Leigh Added comment: Comment on mode of pathogenicity: Activating variants responsible for phenotype
Genetic epilepsy syndromes v0.739 BRAF Sarah Leigh Mode of pathogenicity for gene: BRAF was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Genetic epilepsy syndromes v0.738 PET100 Rebecca Foulger Mode of inheritance for gene: PET100 was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.737 PET100 Rebecca Foulger Phenotypes for gene: PET100 were changed from to Mitochondrial complex IV deficiency, 220110; seizures
Intellectual disability v2.531 NFIB Konstantinos Varvagiannis gene: NFIB was added
gene: NFIB was added to Intellectual disability. Sources: Expert Review,Literature
Mode of inheritance for gene: NFIB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NFIB were set to 30388402
Phenotypes for gene: NFIB were set to Global developmental delay; Intellectual disability; Macrocephaly
Penetrance for gene: NFIB were set to unknown
Review for gene: NFIB was set to GREEN
Added comment: Schanze et al. (PMID: 30388402) report on the phenotype related to NFIB haploinsufficiency.

10 individuals with intragenic NFIB or larger deletions encompassing also other genes as well as 8 individuals with nucleotide variants (5 loss-of-function and 3 missense ones) are described.

Intellectual disability was a universal feature while macrocephaly was noted in the majority of the patients. The phenotype of individuals deletions was similar to the phenotype of intragenic mutations as also seems to be the case with the degree of ID.

Functional studies support loss of function for the pathogenic missense variants reported. Cortical-specific knockout of Nfib in mice results in enlargement of the cortex.

While most of the variants occurred as de novo events, a few individuals had inherited a variant (deletion or nucleotide variant) from a similarly affected parent.

As a result, this gene can be considered for inclusion in the ID panel as green.
Sources: Expert Review, Literature
Genetic epilepsy syndromes v0.736 PET100 Rebecca Foulger commented on gene: PET100
Genetic epilepsy syndromes v0.736 BRAF Sarah Leigh Publications for gene: BRAF were set to
Genetic epilepsy syndromes v0.735 BRAF Sarah Leigh Phenotypes for gene: BRAF were changed from to Cardiofaciocutaneous syndrome 115150; LEOPARD syndrome 3 613707
Genetic epilepsy syndromes v0.734 BRAF Sarah Leigh Mode of inheritance for gene: BRAF was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic epilepsy syndromes v0.733 BOLA3 Sarah Leigh Classified gene: BOLA3 as Green List (high evidence)
Genetic epilepsy syndromes v0.733 BOLA3 Sarah Leigh Gene: bola3 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.732 BOLA3 Sarah Leigh Marked gene: BOLA3 as ready
Genetic epilepsy syndromes v0.732 BOLA3 Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least one truncating variant reported in 2 ethnically diverse unrelated cases of Multiple mitochondrial dysfunctions syndrome 2 with hyperglycinemia 614299. Supportive in vitro studies show are also presented (PMID 24334290).
Genetic epilepsy syndromes v0.732 BOLA3 Sarah Leigh Gene: bola3 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v0.732 BOLA3 Sarah Leigh Mode of inheritance for gene: BOLA3 was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.731 PET100 Rebecca Foulger Publications for gene: PET100 were set to
Genetic epilepsy syndromes v0.730 BOLA3 Sarah Leigh Publications for gene: BOLA3 were set to
Genetic epilepsy syndromes v0.729 SURF1 Rebecca Foulger Mode of inheritance for gene: SURF1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.728 SURF1 Rebecca Foulger Phenotypes for gene: SURF1 were changed from to Leigh syndrome, due to COX IV deficiency, 256000
Genetic epilepsy syndromes v0.727 IFIH1 Rebecca Foulger Classified gene: IFIH1 as Green List (high evidence)
Genetic epilepsy syndromes v0.727 IFIH1 Rebecca Foulger Gene: ifih1 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.726 TBC1D20 Rebecca Foulger Marked gene: TBC1D20 as ready
Genetic epilepsy syndromes v0.726 TBC1D20 Rebecca Foulger Gene: tbc1d20 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v0.726 TBC1D20 Rebecca Foulger Tag watchlist tag was added to gene: TBC1D20.
Genetic epilepsy syndromes v0.726 TBC1D20 Rebecca Foulger Classified gene: TBC1D20 as Amber List (moderate evidence)
Genetic epilepsy syndromes v0.726 TBC1D20 Rebecca Foulger Added comment: Comment on list classification: Kept rating as Amber: Variants in TBC1D20 are currently probable in DD-G2P for causing Warburg micro syndrome 4. Warburg micro syndrome 4 can present with seizures, but currently only 2 unrelated families reported in PMID:24239381 (including febrile seizures in 1 patient). Therefore require further epileptic cases before rating as diagnostic.
Genetic epilepsy syndromes v0.726 TBC1D20 Rebecca Foulger Gene: tbc1d20 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v0.725 TBC1D20 Rebecca Foulger Phenotypes for gene: TBC1D20 were changed from Warburg micro syndrome 4, MIM#615663; seizures to Warburg micro syndrome 4, 615663; seizures
Genetic epilepsy syndromes v0.724 TBC1D20 Rebecca Foulger Phenotypes for gene: TBC1D20 were changed from to Warburg micro syndrome 4, MIM#615663; seizures
Genetic epilepsy syndromes v0.723 TBC1D20 Rebecca Foulger commented on gene: TBC1D20
Genetic epilepsy syndromes v0.723 TBC1D20 Rebecca Foulger Publications for gene: TBC1D20 were set to
Genetic epilepsy syndromes v0.722 BOLA3 Sarah Leigh Phenotypes for gene: BOLA3 were changed from to Multiple mitochondrial dysfunctions syndrome 2 with hyperglycinemia 614299
Genetic epilepsy syndromes v0.721 BCS1L Sarah Leigh Marked gene: BCS1L as ready
Genetic epilepsy syndromes v0.721 BCS1L Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene for GRACILE syndrome 603358. At least 5 variants reported in 3 unrelated cases.
Genetic epilepsy syndromes v0.721 BCS1L Sarah Leigh Gene: bcs1l has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.721 BCS1L Sarah Leigh Classified gene: BCS1L as Green List (high evidence)
Genetic epilepsy syndromes v0.721 BCS1L Sarah Leigh Gene: bcs1l has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.720 BCS1L Sarah Leigh Phenotypes for gene: BCS1L were changed from Mitochondrial complex III deficiency, nuclear type 1 124000; Leigh syndrome 256000 to Mitochondrial complex III deficiency, nuclear type 1 124000; Leigh syndrome 256000; GRACILE syndrome 603358
Genetic epilepsy syndromes v0.719 BCS1L Sarah Leigh Publications for gene: BCS1L were set to
Genetic epilepsy syndromes v0.718 TBC1D20 Rebecca Foulger Mode of inheritance for gene: TBC1D20 was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.717 TBCD Rebecca Foulger Marked gene: TBCD as ready
Genetic epilepsy syndromes v0.717 TBCD Rebecca Foulger Gene: tbcd has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.717 TBCD Rebecca Foulger Classified gene: TBCD as Green List (high evidence)
Genetic epilepsy syndromes v0.717 TBCD Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green. Green review. Confirmed DD-G2P gene for Early-Onset Neurodegenerative Encephalopathy, which can present with seizures. Sufficient cases of seizures (>3) in PMID:27666370 and PMID:27666374 for inclusion on panel.
Genetic epilepsy syndromes v0.717 TBCD Rebecca Foulger Gene: tbcd has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.716 TBCD Rebecca Foulger Phenotypes for gene: TBCD were changed from Encephalopathy, progressive, early-onset, with brain atrophy and thin corpus callosum, 617193; seizures to Encephalopathy, progressive, early-onset, with brain atrophy and thin corpus callosum, 617193; seizures; West syndrome
Genetic epilepsy syndromes v0.715 TBCD Rebecca Foulger commented on gene: TBCD: In 8 children from 4 unrelated families, Miyake et al (PMID:27666374) identified homozygous or compound het variants in TBCD. Seizures were reported in 3 families (Table 2) and were reported as GTS (Chinese family 3), GTS/GTCS (Israel family 4) and West syndrome/cataplexy (Japanese Family 2).
Genetic epilepsy syndromes v0.715 TBCD Rebecca Foulger commented on gene: TBCD
Polycystic liver disease v0.28 Ivone Leong Panel status changed from internal to public
Genetic epilepsy syndromes v0.715 TBCD Rebecca Foulger Mode of inheritance for gene: TBCD was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.714 TBCD Rebecca Foulger Publications for gene: TBCD were set to
Genetic epilepsy syndromes v0.713 TBCD Rebecca Foulger Phenotypes for gene: TBCD were changed from to Encephalopathy, progressive, early-onset, with brain atrophy and thin corpus callosum, 617193; seizures
Genetic epilepsy syndromes v0.712 TBCK Rebecca Foulger Marked gene: TBCK as ready
Genetic epilepsy syndromes v0.712 TBCK Rebecca Foulger Gene: tbck has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.712 BCS1L Sarah Leigh Added comment: Comment on phenotypes: Both of these phenotypes include seizures as part of their phenotypic features
Genetic epilepsy syndromes v0.712 BCS1L Sarah Leigh Phenotypes for gene: BCS1L were changed from Mitochondrial complex III deficiency, nuclear type 1 124000 to Mitochondrial complex III deficiency, nuclear type 1 124000; Leigh syndrome 256000
Genetic epilepsy syndromes v0.711 TBCK Rebecca Foulger Classified gene: TBCK as Green List (high evidence)
Genetic epilepsy syndromes v0.711 TBCK Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green: Green review plus confirmed DD-G2P gene for Severe Infantile Syndromic Encephalopathy, which can present with seizures. Sufficient (>3) unrelated cases of seizures in PMID:27040692 and PMID:27040691 for inclusion on panel.
Genetic epilepsy syndromes v0.711 TBCK Rebecca Foulger Gene: tbck has been classified as Green List (High Evidence).
Congenital hyperinsulinism v1.3 Ellen McDonagh Panel name changed from Hyperinsulinism to Congenital hyperinsulinism
List of related panels changed from to Hyperinsulinism
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Genetic epilepsy syndromes v0.710 BCS1L Sarah Leigh Phenotypes for gene: BCS1L were changed from to Mitochondrial complex III deficiency, nuclear type 1 124000
Inherited phaeochromocytoma and paraganglioma v1.3 Ellen McDonagh Panel name changed from Neuro-endocrine Tumours- PCC and PGL to Inherited phaeochromocytoma and paraganglioma
List of related panels changed from to Neuro-endocrine Tumours- PCC and PGL
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Genetic epilepsy syndromes v0.709 BCS1L Sarah Leigh Mode of inheritance for gene: BCS1L was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.708 TBCK Rebecca Foulger commented on gene: TBCK: Bhoj et al. (2016, PMID:27040691) reported 13 patients from 9 unrelated families with IHPRF. Seven individuals from five families had seizures, and biallelic variants in TBCK.
Endocrine neoplasia v1.6 Ellen McDonagh Panel name changed from Multiple endocrine tumours to Multiple endocrine neoplasia type 1
List of related panels changed from to Multiple endocrine tumours
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Genetic epilepsy syndromes v0.708 TBCK Rebecca Foulger commented on gene: TBCK
Genetic epilepsy syndromes v0.708 TBCK Rebecca Foulger Phenotypes for gene: TBCK were changed from Hypotonia, infantile, with psychomotor retardation and characteristic facies 3, 616900 to Hypotonia, infantile, with psychomotor retardation and characteristic facies 3, 616900; seizures
Genetic epilepsy syndromes v0.707 TBCK Rebecca Foulger Publications for gene: TBCK were set to
Hypogonadotropic hypogonadism v1.15 Ellen McDonagh Panel name changed from Idiopathic hypogonadotropic hypogonadism to Hypogonadotropic hypogonadism
List of related panels changed from Kallmann syndrome; Kallmann syndrom to Kallmann syndrome; Kallmann syndrom; Idiopathic hypogonadotropic hypogonadism
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Familial hypoparathyroidism v1.7 Ellen McDonagh Panel name changed from Familial or syndromic hypoparathyroidism to Familial hypoparathyroidism
List of related panels changed from to Familial or syndromic hypoparathyroidism
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Congenital adrenal hypoplasia v1.6 Ellen McDonagh List of related panels changed from to
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Genetic epilepsy syndromes v0.706 BCKDHB Sarah Leigh Marked gene: BCKDHB as ready
Genetic epilepsy syndromes v0.706 BCKDHB Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 6 variants reported in 5 unrelated cases of Maple syrup urine disease, Classic type Ib 248600.
Genetic epilepsy syndromes v0.706 BCKDHB Sarah Leigh Gene: bckdhb has been classified as Green List (High Evidence).
Severe early-onset obesity v1.6 Ellen McDonagh Panel name changed from Significant early-onset obesity +/- other endocrine features and short stature to Severe early-onset obesity
List of related panels changed from Significant early-onset obesity with or without other endocrine features and short stature to Significant early-onset obesity with or without other endocrine features and short stature; Significant early-onset obesity +/- other endocrine features and short stature
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Genetic epilepsy syndromes v0.706 BCKDHB Sarah Leigh Added comment: Comment on phenotypes: Seizures are a feature of Maple syrup urine disease, Classic type Ib 248600
Genetic epilepsy syndromes v0.706 BCKDHB Sarah Leigh Phenotypes for gene: BCKDHB were changed from Maple syrup urine disease, type Ib 248600 to Maple syrup urine disease, type Ib 248600
Genetic epilepsy syndromes v0.705 BCKDHB Sarah Leigh Classified gene: BCKDHB as Green List (high evidence)
Genetic epilepsy syndromes v0.705 BCKDHB Sarah Leigh Gene: bckdhb has been classified as Green List (High Evidence).
Disorders of sex development v1.25 Ellen McDonagh List of related panels changed from to
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Genetic epilepsy syndromes v0.704 BCKDHB Sarah Leigh Phenotypes for gene: BCKDHB were changed from to Maple syrup urine disease, type Ib 248600
Hyperthyroidism v1.5 Ellen McDonagh Panel name changed from Resistance to thyroid hormone to Hyperthyroidism
List of related panels changed from to Resistance to thyroid hormone
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Genetic epilepsy syndromes v0.703 TBCK Rebecca Foulger Mode of inheritance for gene: TBCK was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.702 TBCK Rebecca Foulger Phenotypes for gene: TBCK were changed from Hypotonia, infantile, with psychomotor retardation and characteristic facies 3,616900 to Hypotonia, infantile, with psychomotor retardation and characteristic facies 3, 616900
Genetic epilepsy syndromes v0.701 BCKDHB Sarah Leigh Mode of inheritance for gene: BCKDHB was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.700 TBCK Rebecca Foulger Phenotypes for gene: TBCK were changed from to Hypotonia, infantile, with psychomotor retardation and characteristic facies 3,616900
Hearing loss v1.49 Ellen McDonagh List of related panels changed from Congenital hearing impairment;Autosomal dominant deafness;Congenital hearing impairment (profound/severe) to Congenital hearing impairment; Autosomal dominant deafness; Congenital hearing impairment (profound/severe)
Genetic epilepsy syndromes v0.699 BCKDHA Sarah Leigh Marked gene: BCKDHA as ready
Genetic epilepsy syndromes v0.699 BCKDHA Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 8 variants reported in unrelated cases of Maple syrup urine disease, Classic type Ia 248600.
Genetic epilepsy syndromes v0.699 BCKDHA Sarah Leigh Gene: bckdha has been classified as Green List (High Evidence).
Hearing loss v1.48 Ellen McDonagh Panel name changed from Congenital hearing impairment (profound/severe) to Hearing loss
List of related panels changed from Congenital hearing impairment; Autosomal dominant deafness to Congenital hearing impairment;Autosomal dominant deafness;Congenital hearing impairment (profound/severe)
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Genetic epilepsy syndromes v0.699 BCKDHA Sarah Leigh Classified gene: BCKDHA as Green List (high evidence)
Genetic epilepsy syndromes v0.699 BCKDHA Sarah Leigh Gene: bckdha has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.698 BCKDHA Sarah Leigh Added comment: Comment on phenotypes: Seizures are a feature of Maple syrup urine disease, Classic type Ia 248600
Genetic epilepsy syndromes v0.698 BCKDHA Sarah Leigh Phenotypes for gene: BCKDHA were changed from Maple syrup urine disease, type Ia 248600 to Maple syrup urine disease, type Ia 248600
Genetic epilepsy syndromes v0.697 BCKDHA Sarah Leigh Publications for gene: BCKDHA were set to
Polycystic liver disease v0.27 PKD1 Ivone Leong Source Expert Review Green was added to PKD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Polycystic liver disease v0.27 STN1 Ivone Leong Source Expert Review Amber was added to STN1.
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Polycystic liver disease v0.27 PEX14 Ivone Leong Source Expert Review Red was added to PEX14.
Polycystic liver disease v0.27 PEX1 Ivone Leong Source Expert Review Amber was added to PEX1.
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Polycystic liver disease v0.27 NOTCH2 Ivone Leong Source Expert Review Amber was added to NOTCH2.
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Polycystic liver disease v0.27 JAG1 Ivone Leong Source Expert Review Amber was added to JAG1.
Polycystic liver disease v0.27 HOGA1 Ivone Leong Source Expert Review Red was added to HOGA1.
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Polycystic liver disease v0.27 GRHPR Ivone Leong Source Expert Review Red was added to GRHPR.
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Polycystic liver disease v0.27 EYA1 Ivone Leong Source Expert Review Red was added to EYA1.
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Polycystic liver disease v0.27 CPT2 Ivone Leong Source Expert Review Red was added to CPT2.
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Polycystic liver disease v0.27 CLDN19 Ivone Leong Source Expert Review Red was added to CLDN19.
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Polycystic liver disease v0.27 CLDN16 Ivone Leong Source Expert Review Red was added to CLDN16.
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Polycystic liver disease v0.27 BSND Ivone Leong Source Expert Review Red was added to BSND.
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Polycystic liver disease v0.27 BICC1 Ivone Leong Source Expert Review Red was added to BICC1.
Polycystic liver disease v0.27 TERC Ivone Leong Source Expert Review Amber was added to TERC.
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Polycystic liver disease v0.27 RTEL1 Ivone Leong Source Expert Review Amber was added to RTEL1.
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Polycystic liver disease v0.27 WRAP53 Ivone Leong Source Expert Review Red was added to WRAP53.
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Polycystic liver disease v0.27 TERT Ivone Leong Source Expert Review Amber was added to TERT.
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Polycystic liver disease v0.27 NOP10 Ivone Leong Source Expert Review Red was added to NOP10.
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Polycystic liver disease v0.27 TINF2 Ivone Leong Source Expert Review Red was added to TINF2.
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Polycystic liver disease v0.27 DKC1 Ivone Leong Source Expert Review Red was added to DKC1.
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Polycystic liver disease v0.27 DGUOK Ivone Leong Source Expert Review Amber was added to DGUOK.
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Polycystic liver disease v0.27 TMEM67 Ivone Leong Source Expert Review Green was added to TMEM67.
Polycystic liver disease v0.27 SEC61B Ivone Leong Source Expert Review Amber was added to SEC61B.
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Polycystic liver disease v0.27 RSPH9 Ivone Leong Source Expert Review Red was added to RSPH9.
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Polycystic liver disease v0.27 RSPH4A Ivone Leong Source Expert Review Red was added to RSPH4A.
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Polycystic liver disease v0.27 REN Ivone Leong Source Expert Review Red was added to REN.
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Polycystic liver disease v0.27 PKHD1 Ivone Leong Source Expert Review Green was added to PKHD1.
Polycystic liver disease v0.27 NME8 Ivone Leong Source Expert Review Red was added to NME8.
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Polycystic liver disease v0.27 LRP5 Ivone Leong Source Expert Review Green was added to LRP5.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Polycystic liver disease v0.27 GANAB Ivone Leong Source Expert Review Green was added to GANAB.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Polycystic liver disease v0.27 DNAL1 Ivone Leong Source Expert Review Red was added to DNAL1.
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Polycystic liver disease v0.27 DNAI2 Ivone Leong Source Expert Review Red was added to DNAI2.
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Polycystic liver disease v0.27 DNAI1 Ivone Leong Source Expert Review Red was added to DNAI1.
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Polycystic liver disease v0.27 DNAH5 Ivone Leong Source Expert Review Red was added to DNAH5.
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Polycystic liver disease v0.27 DNAH11 Ivone Leong Source Expert Review Red was added to DNAH11.
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Polycystic liver disease v0.27 DNAAF3 Ivone Leong Source Expert Review Red was added to DNAAF3.
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Polycystic liver disease v0.27 DNAAF2 Ivone Leong Source Expert Review Red was added to DNAAF2.
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Polycystic liver disease v0.27 DNAAF1 Ivone Leong Source Expert Review Red was added to DNAAF1.
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Polycystic liver disease v0.27 CCDC40 Ivone Leong Source Expert Review Red was added to CCDC40.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Polycystic liver disease v0.27 CCDC39 Ivone Leong Source Expert Review Red was added to CCDC39.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Polycystic liver disease v0.27 B9D1 Ivone Leong Source Expert Review Green was added to B9D1.
Polycystic liver disease v0.27 ALG8 Ivone Leong Source Expert Review Green was added to ALG8.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Polycystic liver disease v0.27 AGT Ivone Leong Source Expert Review Red was added to AGT.
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Genetic epilepsy syndromes v0.696 BCKDHA Sarah Leigh Mode of inheritance for gene: BCKDHA was changed from to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v2.531 PCGF2 Louise Daugherty edited their review of gene: PCGF2: Changed rating: GREEN
Genetic epilepsy syndromes v0.695 BCKDHA Sarah Leigh Phenotypes for gene: BCKDHA were changed from to Maple syrup urine disease, type Ia 248600
Primary lymphoedema v1.31 Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Familial hypercholesterolaemia v1.20 Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Polycystic liver disease v0.26 PKD1 Ivone Leong reviewed gene: PKD1: Rating: GREEN; Mode of pathogenicity: ; Publications: 8554072; Phenotypes: ; Mode of inheritance:
Polycystic liver disease v0.26 STN1 Ivone Leong reviewed gene: STN1: Rating: AMBER; Mode of pathogenicity: ; Publications: 27432940; Phenotypes: ; Mode of inheritance:
Polycystic liver disease v0.26 PEX14 Ivone Leong reviewed gene: PEX14: Rating: RED; Mode of pathogenicity: ; Publications: 15146459; Phenotypes: ; Mode of inheritance:
Polycystic liver disease v0.26 PEX1 Ivone Leong reviewed gene: PEX1: Rating: AMBER; Mode of pathogenicity: ; Publications: 12032265; Phenotypes: ; Mode of inheritance:
Polycystic liver disease v0.26 NOTCH2 Ivone Leong reviewed gene: NOTCH2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Polycystic liver disease v0.26 JAG1 Ivone Leong reviewed gene: JAG1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Polycystic liver disease v0.26 HOGA1 Ivone Leong reviewed gene: HOGA1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Polycystic liver disease v0.26 GRHPR Ivone Leong reviewed gene: GRHPR: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Polycystic liver disease v0.26 EYA1 Ivone Leong reviewed gene: EYA1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Polycystic liver disease v0.26 CPT2 Ivone Leong reviewed gene: CPT2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Polycystic liver disease v0.26 CLDN19 Ivone Leong reviewed gene: CLDN19: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Polycystic liver disease v0.26 CLDN16 Ivone Leong reviewed gene: CLDN16: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Polycystic liver disease v0.26 BSND Ivone Leong reviewed gene: BSND: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Polycystic liver disease v0.26 BICC1 Ivone Leong reviewed gene: BICC1: Rating: RED; Mode of pathogenicity: ; Publications: 21922595; Phenotypes: ; Mode of inheritance:
Polycystic liver disease v0.26 TERC Ivone Leong reviewed gene: TERC: Rating: AMBER; Mode of pathogenicity: ; Publications: 22341970, 21436073, 19936245; Phenotypes: ; Mode of inheritance:
Polycystic liver disease v0.26 RTEL1 Ivone Leong reviewed gene: RTEL1: Rating: AMBER; Mode of pathogenicity: ; Publications: 28495916; Phenotypes: ; Mode of inheritance:
Polycystic liver disease v0.26 WRAP53 Ivone Leong reviewed gene: WRAP53: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Polycystic liver disease v0.26 TERT Ivone Leong reviewed gene: TERT: Rating: AMBER; Mode of pathogenicity: ; Publications: 19936245, 21483807, 21436073; Phenotypes: ; Mode of inheritance:
Polycystic liver disease v0.26 NOP10 Ivone Leong reviewed gene: NOP10: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Polycystic liver disease v0.26 TINF2 Ivone Leong reviewed gene: TINF2: Rating: RED; Mode of pathogenicity: ; Publications: 21477109; Phenotypes: ; Mode of inheritance:
Polycystic liver disease v0.26 DKC1 Ivone Leong reviewed gene: DKC1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Polycystic liver disease v0.26 DGUOK Ivone Leong reviewed gene: DGUOK: Rating: AMBER; Mode of pathogenicity: ; Publications: 30234759, 11687800, 12210798, 25129007 ; Phenotypes: ; Mode of inheritance:
Polycystic liver disease v0.26 TMEM67 Ivone Leong reviewed gene: TMEM67: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Polycystic liver disease v0.26 SEC61B Ivone Leong reviewed gene: SEC61B: Rating: AMBER; Mode of pathogenicity: ; Publications: 28862642; Phenotypes: ; Mode of inheritance:
Polycystic liver disease v0.26 RSPH9 Ivone Leong reviewed gene: RSPH9: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Polycystic liver disease v0.26 RSPH4A Ivone Leong reviewed gene: RSPH4A: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Polycystic liver disease v0.26 REN Ivone Leong reviewed gene: REN: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Polycystic liver disease v0.26 PKHD1 Ivone Leong reviewed gene: PKHD1: Rating: GREEN; Mode of pathogenicity: ; Publications: 28862642, 11337358, 11135065; Phenotypes: ; Mode of inheritance:
Polycystic liver disease v0.26 NME8 Ivone Leong reviewed gene: NME8: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Polycystic liver disease v0.26 LRP5 Ivone Leong reviewed gene: LRP5: Rating: GREEN; Mode of pathogenicity: ; Publications: 25920554; Phenotypes: ; Mode of inheritance:
Polycystic liver disease v0.26 GANAB Ivone Leong reviewed gene: GANAB: Rating: GREEN; Mode of pathogenicity: ; Publications: 28862642, 27259053, 29243290 ; Phenotypes: ; Mode of inheritance:
Polycystic liver disease v0.26 DNAL1 Ivone Leong reviewed gene: DNAL1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Polycystic liver disease v0.26 DNAI2 Ivone Leong reviewed gene: DNAI2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Polycystic liver disease v0.26 DNAI1 Ivone Leong reviewed gene: DNAI1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Polycystic liver disease v0.26 DNAH5 Ivone Leong reviewed gene: DNAH5: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Polycystic liver disease v0.26 DNAH11 Ivone Leong reviewed gene: DNAH11: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Polycystic liver disease v0.26 DNAAF3 Ivone Leong reviewed gene: DNAAF3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Polycystic liver disease v0.26 DNAAF2 Ivone Leong reviewed gene: DNAAF2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Polycystic liver disease v0.26 DNAAF1 Ivone Leong reviewed gene: DNAAF1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Polycystic liver disease v0.26 CCDC40 Ivone Leong reviewed gene: CCDC40: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Polycystic liver disease v0.26 CCDC39 Ivone Leong reviewed gene: CCDC39: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Polycystic liver disease v0.26 B9D1 Ivone Leong reviewed gene: B9D1: Rating: GREEN; Mode of pathogenicity: ; Publications: 21493627, 21763481; Phenotypes: ; Mode of inheritance:
Polycystic liver disease v0.26 ALG8 Ivone Leong reviewed gene: ALG8: Rating: GREEN; Mode of pathogenicity: ; Publications: 15235028, 28375157 ; Phenotypes: ; Mode of inheritance:
Polycystic liver disease v0.26 AGT Ivone Leong reviewed gene: AGT: Rating: RED; Mode of pathogenicity: ; Publications: 16116425, 17036344; Phenotypes: ; Mode of inheritance:
Thoracic aortic aneurysm or dissection v1.76 Ellen McDonagh Panel name changed from Familial Thoracic Aortic Aneurysm Disease to Thoracic aortic aneurysm or dissection
List of related panels changed from Familial retinal arteriolar tortuosity; FTAAD to Familial retinal arteriolar tortuosity;FTAAD;Familial Thoracic Aortic Aneurysm Disease
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Mitochondrial disorders v1.69 Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Severe microcephaly v1.38 Ellen McDonagh Panel name changed from Primary Microcephaly - Microcephalic Dwarfism Spectrum to Severe microcephaly
List of related panels changed from to Primary Microcephaly - Microcephalic Dwarfism Spectrum
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Genetic epilepsy syndromes v0.694 ATP7A Sarah Leigh Marked gene: ATP7A as ready
Genetic epilepsy syndromes v0.694 ATP7A Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 3 variants reported in 3 unrelated cases of Menkes disease 309400 with seizures.
Genetic epilepsy syndromes v0.694 ATP7A Sarah Leigh Gene: atp7a has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.694 ATP7A Sarah Leigh Classified gene: ATP7A as Green List (high evidence)
Genetic epilepsy syndromes v0.694 ATP7A Sarah Leigh Gene: atp7a has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.693 ATP7A Sarah Leigh Publications for gene: ATP7A were set to
Hydrocephalus v1.23 Ellen McDonagh List of related panels changed from to
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Holoprosencephaly v1.5 Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Genetic epilepsy syndromes v0.692 ATP7A Sarah Leigh Mode of inheritance for gene: ATP7A was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Genetic epilepsy syndromes v0.691 ATP7A Sarah Leigh Phenotypes for gene: ATP7A were changed from to Menkes disease 309400
Intellectual disability v2.531 Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Diabetes - neonatal onset v1.8 Ellen McDonagh Panel name changed from Neonatal diabetes diagnosed <6 months to Diabetes - neonatal onset
List of related panels changed from Neonatal diabetes (diagnosed less than 6 months);Neonatal diabetes to Neonatal diabetes (diagnosed less than 6 months);Neonatal diabetes;Neonatal diabetes diagnosed <6 months
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Skeletal dysplasia v1.128 Ellen McDonagh Panel name changed from Unexplained skeletal dysplasia to Skeletal dysplasia
List of related panels changed from Skeletal dysplasia to Unexplained skeletal dysplasia
Genetic epilepsy syndromes v0.690 SMS Sarah Leigh Marked gene: SMS as ready
Genetic epilepsy syndromes v0.690 SMS Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 3 variants reported in unrelated cases of Mental retardation, X-linked, Snyder-Robinson type 309583 manifesting seizures.
Genetic epilepsy syndromes v0.690 SMS Sarah Leigh Gene: sms has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.690 SMS Sarah Leigh Classified gene: SMS as Green List (high evidence)
Genetic epilepsy syndromes v0.690 SMS Sarah Leigh Gene: sms has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.689 SMS Sarah Leigh Publications for gene: SMS were set to
Genetic epilepsy syndromes v0.688 SMS Sarah Leigh Phenotypes for gene: SMS were changed from to Mental retardation, X-linked, Snyder-Robinson type 309583
Genetic epilepsy syndromes v0.687 PCDH12 Sarah Leigh Marked gene: PCDH12 as ready
Genetic epilepsy syndromes v0.687 PCDH12 Sarah Leigh Added comment: Comment when marking as ready: Associated with phenotype in OMIM and not in Gen2Phen. At least 3 truncating variants identified, one variant has been shown to be a founder in four consanguineous Palestinian Israeli families following haplotype analysis, however, functional studies demonstrate nonsense-mediated mRNA decay and likely a complete loss of function in the cells from one affected family member (PMID 27164683). The other two variants were found as compound heterozygotes in a Japanese patient with dyskinetic cerebral palsy and epilepsy (PMID 28804758).
Genetic epilepsy syndromes v0.687 PCDH12 Sarah Leigh Gene: pcdh12 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.687 PCDH12 Sarah Leigh Classified gene: PCDH12 as Green List (high evidence)
Genetic epilepsy syndromes v0.687 PCDH12 Sarah Leigh Gene: pcdh12 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.686 SMS Sarah Leigh Mode of inheritance for gene: SMS was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Genetic epilepsy syndromes v0.685 PCDH12 Sarah Leigh Gene: pcdh12 has been classified as Red List (Low Evidence).
Polycystic liver disease v0.25 FANCD2 Ivone Leong gene: FANCD2 was added
gene: FANCD2 was added to Ductal plate malformation (DPM). Sources: Expert list
Mode of inheritance for gene: FANCD2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FANCD2 were set to Fanconi anemia, complementation group D2 (227646)
Polycystic liver disease v0.25 STN1 Ivone Leong gene: STN1 was added
gene: STN1 was added to Ductal plate malformation (DPM). Sources: Expert list
Mode of inheritance for gene: STN1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: STN1 were set to Cerebroretinal microangiopathy with calcifications and cysts 2 (617341)
Polycystic liver disease v0.25 SLC4A1 Ivone Leong gene: SLC4A1 was added
gene: SLC4A1 was added to Ductal plate malformation (DPM). Sources: Radboud University Medical Center, Nijmegen, Expert list
Mode of inheritance for gene: SLC4A1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: SLC4A1 were set to Renal tubular acidosis, distal, AR (611590); Renal tubular acidosis, distal, AD (179800)
Polycystic liver disease v0.25 SLC41A1 Ivone Leong gene: SLC41A1 was added
gene: SLC41A1 was added to Ductal plate malformation (DPM). Sources: Expert list
Mode of inheritance for gene: SLC41A1 was set to Unknown
Phenotypes for gene: SLC41A1 were set to No OMIM
Polycystic liver disease v0.25 SLC12A3 Ivone Leong gene: SLC12A3 was added
gene: SLC12A3 was added to Ductal plate malformation (DPM). Sources: Radboud University Medical Center, Nijmegen, Expert list
Mode of inheritance for gene: SLC12A3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC12A3 were set to Gitelman syndrome (263800)
Polycystic liver disease v0.25 SIX5 Ivone Leong gene: SIX5 was added
gene: SIX5 was added to Ductal plate malformation (DPM). Sources: Radboud University Medical Center, Nijmegen, Expert list
Mode of inheritance for gene: SIX5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: SIX5 were set to Branchiootorenal syndrome 2 (610896)
Polycystic liver disease v0.25 PKD1L1 Ivone Leong gene: PKD1L1 was added
gene: PKD1L1 was added to Ductal plate malformation (DPM). Sources: Radboud University Medical Center, Nijmegen, Expert list
Mode of inheritance for gene: PKD1L1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PKD1L1 were set to Heterotaxy, visceral, 8, autosomal (617205)
Polycystic liver disease v0.25 PEX7 Ivone Leong gene: PEX7 was added
gene: PEX7 was added to Ductal plate malformation (DPM). Sources: Radboud University Medical Center, Nijmegen, Expert list
Mode of inheritance for gene: PEX7 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PEX7 were set to Peroxisome biogenesis disorder 9B (614879)
Polycystic liver disease v0.25 PEX6 Ivone Leong gene: PEX6 was added
gene: PEX6 was added to Ductal plate malformation (DPM). Sources: Radboud University Medical Center, Nijmegen, Expert list
Mode of inheritance for gene: PEX6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PEX6 were set to Peroxisome biogenesis disorder 4A (Zellweger) (614862); Peroxisome biogenesis disorder 4B (614863)
Polycystic liver disease v0.25 PEX5 Ivone Leong gene: PEX5 was added
gene: PEX5 was added to Ductal plate malformation (DPM). Sources: Radboud University Medical Center, Nijmegen, Expert list
Mode of inheritance for gene: PEX5 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PEX5 were set to Peroxisome biogenesis disorder 2B (202370); Peroxisome biogenesis disorder 2A (Zellweger) (214110)
Polycystic liver disease v0.25 PEX3 Ivone Leong gene: PEX3 was added
gene: PEX3 was added to Ductal plate malformation (DPM). Sources: Radboud University Medical Center, Nijmegen, Expert list
Mode of inheritance for gene: PEX3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PEX3 were set to ?Peroxisome biogenesis disorder 10B (617370); Peroxisome biogenesis disorder 10A (Zellweger) (614882)
Polycystic liver disease v0.25 PEX26 Ivone Leong gene: PEX26 was added
gene: PEX26 was added to Ductal plate malformation (DPM). Sources: Radboud University Medical Center, Nijmegen, Expert list
Mode of inheritance for gene: PEX26 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PEX26 were set to Peroxisome biogenesis disorder 7A (Zellweger) (614872); Peroxisome biogenesis disorder 7B (614873)
Polycystic liver disease v0.25 PEX2 Ivone Leong gene: PEX2 was added
gene: PEX2 was added to Ductal plate malformation (DPM). Sources: Radboud University Medical Center, Nijmegen, Expert list
Mode of inheritance for gene: PEX2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PEX2 were set to Peroxisome biogenesis disorder 5A (Zellweger) (614866); Peroxisome biogenesis disorder 5B (614867)
Polycystic liver disease v0.25 PEX19 Ivone Leong gene: PEX19 was added
gene: PEX19 was added to Ductal plate malformation (DPM). Sources: Radboud University Medical Center, Nijmegen, Expert list
Mode of inheritance for gene: PEX19 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PEX19 were set to Peroxisome biogenesis disorder 12A (Zellweger) (614886)
Polycystic liver disease v0.25 PEX16 Ivone Leong gene: PEX16 was added
gene: PEX16 was added to Ductal plate malformation (DPM). Sources: Radboud University Medical Center, Nijmegen, Expert list
Mode of inheritance for gene: PEX16 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PEX16 were set to Peroxisome biogenesis disorder 8A (Zellweger) (614876); Peroxisome biogenesis disorder 8B (614877)
Polycystic liver disease v0.25 PEX14 Ivone Leong gene: PEX14 was added
gene: PEX14 was added to Ductal plate malformation (DPM). Sources: Radboud University Medical Center, Nijmegen, Expert list
Mode of inheritance for gene: PEX14 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PEX14 were set to Peroxisome biogenesis disorder 13A (Zellweger) (614887)
Polycystic liver disease v0.25 PEX13 Ivone Leong gene: PEX13 was added
gene: PEX13 was added to Ductal plate malformation (DPM). Sources: Radboud University Medical Center, Nijmegen, Expert list
Mode of inheritance for gene: PEX13 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PEX13 were set to Peroxisome biogenesis disorder 11B (614885); Peroxisome biogenesis disorder 11A (Zellweger) (614883)
Polycystic liver disease v0.25 PEX12 Ivone Leong gene: PEX12 was added
gene: PEX12 was added to Ductal plate malformation (DPM). Sources: Radboud University Medical Center, Nijmegen, Expert list
Mode of inheritance for gene: PEX12 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PEX12 were set to Peroxisome biogenesis disorder 3B (266510); Peroxisome biogenesis disorder 3A (Zellweger) (614859)
Polycystic liver disease v0.25 PEX11B Ivone Leong gene: PEX11B was added
gene: PEX11B was added to Ductal plate malformation (DPM). Sources: Radboud University Medical Center, Nijmegen, Expert list
Mode of inheritance for gene: PEX11B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PEX11B were set to ?Peroxisome biogenesis disorder 14B (614920)
Polycystic liver disease v0.25 PEX10 Ivone Leong gene: PEX10 was added
gene: PEX10 was added to Ductal plate malformation (DPM). Sources: Radboud University Medical Center, Nijmegen, Expert list
Mode of inheritance for gene: PEX10 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PEX10 were set to Peroxisome biogenesis disorder 6A (Zellweger) (614870); Peroxisome biogenesis disorder 6B (614871)
Polycystic liver disease v0.25 PEX1 Ivone Leong gene: PEX1 was added
gene: PEX1 was added to Ductal plate malformation (DPM). Sources: Expert list
Mode of inheritance for gene: PEX1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PEX1 were set to Peroxisome biogenesis disorder 1B (NALD/IRD) (601539); Peroxisome biogenesis disorder 1A (Zellweger) (214100)
Polycystic liver disease v0.25 PAX2 Ivone Leong gene: PAX2 was added
gene: PAX2 was added to Ductal plate malformation (DPM). Sources: Radboud University Medical Center, Nijmegen, Expert list
Mode of inheritance for gene: PAX2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: PAX2 were set to Glomerulosclerosis, focal segmental, 7 (616002); Papillorenal syndrome (120330)
Polycystic liver disease v0.25 NOTCH2 Ivone Leong gene: NOTCH2 was added
gene: NOTCH2 was added to Ductal plate malformation (DPM). Sources: Radboud University Medical Center, Nijmegen, Expert list
Mode of inheritance for gene: NOTCH2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: NOTCH2 were set to Alagille syndrome 2 (610205)
Polycystic liver disease v0.25 MRE11 Ivone Leong gene: MRE11 was added
gene: MRE11 was added to Ductal plate malformation (DPM). Sources: Expert list,Illumina TruGenome Clinical Sequencing Services
Mode of inheritance for gene: MRE11 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MRE11 were set to Ataxia-telangiectasia-like disorder 1 (604391)
Polycystic liver disease v0.25 JAG1 Ivone Leong gene: JAG1 was added
gene: JAG1 was added to Ductal plate malformation (DPM). Sources: Expert list,Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen
Mode of inheritance for gene: JAG1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: JAG1 were set to Alagille syndrome 1 (118450)
Polycystic liver disease v0.25 HOGA1 Ivone Leong gene: HOGA1 was added
gene: HOGA1 was added to Ductal plate malformation (DPM). Sources: Expert list,Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen
Mode of inheritance for gene: HOGA1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: HOGA1 were set to Hyperoxaluria, primary, type III (613616)
Polycystic liver disease v0.25 GRHPR Ivone Leong gene: GRHPR was added
gene: GRHPR was added to Ductal plate malformation (DPM). Sources: Expert list,Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen
Mode of inheritance for gene: GRHPR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GRHPR were set to Hyperoxaluria, primary, type II (260000)
Polycystic liver disease v0.25 EYA1 Ivone Leong gene: EYA1 was added
gene: EYA1 was added to Ductal plate malformation (DPM). Sources: Expert list,Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen
Mode of inheritance for gene: EYA1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: EYA1 were set to Branchiootic syndrome 1 (602588); Branchiootorenal syndrome 1, with or without cataracts (113650)
Polycystic liver disease v0.25 CPT2 Ivone Leong gene: CPT2 was added
gene: CPT2 was added to Ductal plate malformation (DPM). Sources: Expert list,Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen
Mode of inheritance for gene: CPT2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CPT2 were set to CPT II deficiency, infantile (600649); CPT II deficiency, lethal neonatal (608836)
Polycystic liver disease v0.25 CLDN19 Ivone Leong gene: CLDN19 was added
gene: CLDN19 was added to Ductal plate malformation (DPM). Sources: Expert list,Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen
Mode of inheritance for gene: CLDN19 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CLDN19 were set to Hypomagnesemia 5, renal, with ocular involvement (248190)
Polycystic liver disease v0.25 CLDN16 Ivone Leong gene: CLDN16 was added
gene: CLDN16 was added to Ductal plate malformation (DPM). Sources: Expert list,Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen
Mode of inheritance for gene: CLDN16 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CLDN16 were set to Hypomagnesemia 3, renal (248250)
Polycystic liver disease v0.25 CLCNKB Ivone Leong gene: CLCNKB was added
gene: CLCNKB was added to Ductal plate malformation (DPM). Sources: Expert list,Radboud University Medical Center, Nijmegen
Mode of inheritance for gene: CLCNKB was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: CLCNKB were set to Bartter syndrome, type 3 (607364); Bartter syndrome, type 4b, digenic (613090)
Polycystic liver disease v0.25 CCND1 Ivone Leong gene: CCND1 was added
gene: CCND1 was added to Ductal plate malformation (DPM). Sources: Expert list
Mode of inheritance for gene: CCND1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: CCND1 were set to {von Hippel-Lindau syndrome, modifier of} (193300); {Colorectal cancer, susceptibility to} (114500)
Polycystic liver disease v0.25 BSND Ivone Leong gene: BSND was added
gene: BSND was added to Ductal plate malformation (DPM). Sources: Expert list,Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen
Mode of inheritance for gene: BSND was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: BSND were set to Bartter syndrome, type 4a (602522); Sensorineural deafness with mild renal dysfunction (602522)
Polycystic liver disease v0.25 BICC1 Ivone Leong gene: BICC1 was added
gene: BICC1 was added to Ductal plate malformation (DPM). Sources: Expert list
Mode of inheritance for gene: BICC1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: BICC1 were set to {Renal dysplasia, cystic, susceptibility to} (601331)
Craniosynostosis v1.41 Ellen McDonagh Panel name changed from Craniosynostosis syndromes phenotypes to Craniosynostosis
List of related panels changed from Craniosynostosis syndromes to Craniosynostosis syndromes;Craniosynostosis syndromes phenotypes
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Genetic epilepsy syndromes v0.685 PCDH12 Sarah Leigh Phenotypes for gene: PCDH12 were changed from intellectual disability; microcephaly; epilepsy; perithalamic hyperechogenicity; periventricular hyperechogenicity; midbrain abnormalities; hypothalamic abnormalities to Microcephaly, seizures, spasticity, and brain calcification 251280
Genetic epilepsy syndromes v0.684 PCDH12 Sarah Leigh Publications for gene: PCDH12 were set to 27164683
Genetic epilepsy syndromes v0.683 MFSD8 Sarah Leigh Marked gene: MFSD8 as ready
Genetic epilepsy syndromes v0.683 MFSD8 Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 4 variants reported in cases of Ceroid lipofuscinosis, neuronal, 7 610951 with seizures.
Genetic epilepsy syndromes v0.683 MFSD8 Sarah Leigh Gene: mfsd8 has been classified as Green List (High Evidence).
Paediatric disorders - additional genes v0.2 Ellen McDonagh Panel status changed from public to internal
Genetic epilepsy syndromes v0.683 MFSD8 Sarah Leigh Classified gene: MFSD8 as Green List (high evidence)
Genetic epilepsy syndromes v0.683 MFSD8 Sarah Leigh Gene: mfsd8 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.682 MFSD8 Sarah Leigh Mode of inheritance for gene: MFSD8 was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.681 MFSD8 Sarah Leigh Phenotypes for gene: MFSD8 were changed from to Ceroid lipofuscinosis, neuronal, 7 610951
Polycystic liver disease v0.24 TXNDC15 Ivone Leong Source Expert Review Removed was added to TXNDC15.
Rating Changed from Red List (low evidence) to No List (delete)
Polycystic liver disease v0.24 TMEM107 Ivone Leong Source Expert Review Removed was added to TMEM107.
Rating Changed from Red List (low evidence) to No List (delete)
Polycystic liver disease v0.24 TCTEX1D2 Ivone Leong Source Expert Review Removed was added to TCTEX1D2.
Rating Changed from Red List (low evidence) to No List (delete)
Polycystic liver disease v0.24 MAPKBP1 Ivone Leong Source Expert Review Removed was added to MAPKBP1.
Rating Changed from Red List (low evidence) to No List (delete)
Polycystic liver disease v0.24 KIAA0586 Ivone Leong Source Expert Review Removed was added to KIAA0586.
Rating Changed from Red List (low evidence) to No List (delete)
Polycystic liver disease v0.24 IFT52 Ivone Leong Source Expert Review Removed was added to IFT52.
Rating Changed from Red List (low evidence) to No List (delete)
Polycystic liver disease v0.24 DYNC2LI1 Ivone Leong Source Expert Review Removed was added to DYNC2LI1.
Rating Changed from Red List (low evidence) to No List (delete)
Polycystic liver disease v0.24 DDX59 Ivone Leong Source Expert Review Removed was added to DDX59.
Rating Changed from Red List (low evidence) to No List (delete)
Polycystic liver disease v0.24 CSPP1 Ivone Leong Source Expert Review Removed was added to CSPP1.
Rating Changed from Red List (low evidence) to No List (delete)
Polycystic liver disease v0.24 ALMS1 Ivone Leong Source Expert Review Removed was added to ALMS1.
Rating Changed from Red List (low evidence) to No List (delete)
Polycystic liver disease v0.24 WDR34 Ivone Leong Source Expert Review Removed was added to WDR34.
Rating Changed from Amber List (moderate evidence) to No List (delete)
Polycystic liver disease v0.24 TMEM231 Ivone Leong Source Expert Review Removed was added to TMEM231.
Rating Changed from Amber List (moderate evidence) to No List (delete)
Polycystic liver disease v0.24 INVS Ivone Leong Source Expert Review Removed was added to INVS.
Rating Changed from Amber List (moderate evidence) to No List (delete)
Polycystic liver disease v0.24 IFT172 Ivone Leong Source Expert Review Removed was added to IFT172.
Rating Changed from Amber List (moderate evidence) to No List (delete)
Polycystic liver disease v0.24 IFT140 Ivone Leong Source Expert Review Removed was added to IFT140.
Rating Changed from Amber List (moderate evidence) to No List (delete)
Polycystic liver disease v0.24 IFT122 Ivone Leong Source Expert Review Removed was added to IFT122.
Rating Changed from Amber List (moderate evidence) to No List (delete)
Polycystic liver disease v0.24 HYLS1 Ivone Leong Source Expert Review Removed was added to HYLS1.
Rating Changed from Amber List (moderate evidence) to No List (delete)
Polycystic liver disease v0.24 EVC2 Ivone Leong Source Expert Review Removed was added to EVC2.
Rating Changed from Amber List (moderate evidence) to No List (delete)
Polycystic liver disease v0.24 EVC Ivone Leong Source Expert Review Removed was added to EVC.
Rating Changed from Amber List (moderate evidence) to No List (delete)
Polycystic liver disease v0.24 CEP83 Ivone Leong Source Expert Review Removed was added to CEP83.
Rating Changed from Amber List (moderate evidence) to No List (delete)
Polycystic liver disease v0.24 CEP120 Ivone Leong Source Expert Review Removed was added to CEP120.
Rating Changed from Amber List (moderate evidence) to No List (delete)
Polycystic liver disease v0.24 C2CD3 Ivone Leong Source Expert Review Removed was added to C2CD3.
Rating Changed from Amber List (moderate evidence) to No List (delete)
Polycystic liver disease v0.24 ANKS6 Ivone Leong Source Expert Review Removed was added to ANKS6.
Rating Changed from Amber List (moderate evidence) to No List (delete)
Polycystic liver disease v0.24 TTC21B Ivone Leong Source Expert Review Removed was added to TTC21B.
Rating Changed from Green List (high evidence) to No List (delete)
Polycystic liver disease v0.24 TMEM237 Ivone Leong Source Expert Review Removed was added to TMEM237.
Rating Changed from Green List (high evidence) to No List (delete)
Polycystic liver disease v0.24 TCTN3 Ivone Leong Source Expert Review Removed was added to TCTN3.
Rating Changed from Green List (high evidence) to No List (delete)
Polycystic liver disease v0.24 OFD1 Ivone Leong Source Expert Review Removed was added to OFD1.
Rating Changed from Green List (high evidence) to No List (delete)
Polycystic liver disease v0.24 KIF7 Ivone Leong Source Expert Review Removed was added to KIF7.
Rating Changed from Green List (high evidence) to No List (delete)
Polycystic liver disease v0.24 IQCB1 Ivone Leong Source Expert Review Removed was added to IQCB1.
Rating Changed from Green List (high evidence) to No List (delete)
Polycystic liver disease v0.24 INPP5E Ivone Leong Source Expert Review Removed was added to INPP5E.
Rating Changed from Green List (high evidence) to No List (delete)
Polycystic liver disease v0.24 IFT80 Ivone Leong Source Expert Review Removed was added to IFT80.
Rating Changed from Green List (high evidence) to No List (delete)
Polycystic liver disease v0.24 CEP164 Ivone Leong Source Expert Review Removed was added to CEP164.
Rating Changed from Green List (high evidence) to No List (delete)
Polycystic liver disease v0.24 BBS5 Ivone Leong Source Expert Review Removed was added to BBS5.
Rating Changed from Green List (high evidence) to No List (delete)
Polycystic liver disease v0.24 ARL13B Ivone Leong Source Expert Review Removed was added to ARL13B.
Rating Changed from Green List (high evidence) to No List (delete)
Polycystic liver disease v0.24 WDR35 Ivone Leong Source Expert Review Removed was added to WDR35.
Rating Changed from Green List (high evidence) to No List (delete)
Polycystic liver disease v0.24 WDPCP Ivone Leong Source Expert Review Removed was added to WDPCP.
Rating Changed from Green List (high evidence) to No List (delete)
Polycystic liver disease v0.24 TTC8 Ivone Leong Source Expert Review Removed was added to TTC8.
Rating Changed from Green List (high evidence) to No List (delete)
Polycystic liver disease v0.24 TMEM216 Ivone Leong Source Expert Review Removed was added to TMEM216.
Rating Changed from Green List (high evidence) to No List (delete)
Polycystic liver disease v0.24 TMEM138 Ivone Leong Source Expert Review Removed was added to TMEM138.
Rating Changed from Green List (high evidence) to No List (delete)
Polycystic liver disease v0.24 TCTN2 Ivone Leong Source Expert Review Removed was added to TCTN2.
Rating Changed from Green List (high evidence) to No List (delete)
Polycystic liver disease v0.24 TCTN1 Ivone Leong Source Expert Review Removed was added to TCTN1.
Rating Changed from Green List (high evidence) to No List (delete)
Polycystic liver disease v0.24 SDCCAG8 Ivone Leong Source Expert Review Removed was added to SDCCAG8.
Rating Changed from Green List (high evidence) to No List (delete)
Polycystic liver disease v0.24 RPGRIP1L Ivone Leong Source Expert Review Removed was added to RPGRIP1L.
Rating Changed from Green List (high evidence) to No List (delete)
Polycystic liver disease v0.24 NPHP4 Ivone Leong Source Expert Review Removed was added to NPHP4.
Rating Changed from Green List (high evidence) to No List (delete)
Polycystic liver disease v0.24 NPHP3 Ivone Leong Source Expert Review Removed was added to NPHP3.
Rating Changed from Green List (high evidence) to No List (delete)
Polycystic liver disease v0.24 NPHP1 Ivone Leong Source Expert Review Removed was added to NPHP1.
Rating Changed from Green List (high evidence) to No List (delete)
Polycystic liver disease v0.24 NEK8 Ivone Leong Source Expert Review Removed was added to NEK8.
Rating Changed from Green List (high evidence) to No List (delete)
Polycystic liver disease v0.24 NEK1 Ivone Leong Source Expert Review Removed was added to NEK1.
Rating Changed from Green List (high evidence) to No List (delete)
Polycystic liver disease v0.24 MKS1 Ivone Leong Source Expert Review Removed was added to MKS1.
Rating Changed from Green List (high evidence) to No List (delete)
Polycystic liver disease v0.24 MKKS Ivone Leong Source Expert Review Removed was added to MKKS.
Rating Changed from Green List (high evidence) to No List (delete)
Polycystic liver disease v0.24 HNF1B Ivone Leong Source Expert Review Removed was added to HNF1B.
Rating Changed from Green List (high evidence) to No List (delete)
Polycystic liver disease v0.24 DYNC2H1 Ivone Leong Source Expert Review Removed was added to DYNC2H1.
Rating Changed from Green List (high evidence) to No List (delete)
Polycystic liver disease v0.24 CEP41 Ivone Leong Source Expert Review Removed was added to CEP41.
Rating Changed from Green List (high evidence) to No List (delete)
Polycystic liver disease v0.24 CEP104 Ivone Leong Source Expert Review Removed was added to CEP104.
Rating Changed from Red List (low evidence) to No List (delete)
Polycystic liver disease v0.24 CEP290 Ivone Leong Source Expert Review Removed was added to CEP290.
Rating Changed from Green List (high evidence) to No List (delete)
Polycystic liver disease v0.24 CC2D2A Ivone Leong Source Expert Review Removed was added to CC2D2A.
Rating Changed from Green List (high evidence) to No List (delete)
Polycystic liver disease v0.24 C5orf42 Ivone Leong Source Expert Review Removed was added to C5orf42.
Rating Changed from Green List (high evidence) to No List (delete)
Polycystic liver disease v0.24 BBS9 Ivone Leong Source Expert Review Removed was added to BBS9.
Rating Changed from Green List (high evidence) to No List (delete)
Polycystic liver disease v0.24 BBS7 Ivone Leong Source Expert Review Removed was added to BBS7.
Rating Changed from Green List (high evidence) to No List (delete)
Polycystic liver disease v0.24 BBS4 Ivone Leong Source Expert Review Removed was added to BBS4.
Rating Changed from Green List (high evidence) to No List (delete)
Polycystic liver disease v0.24 BBS2 Ivone Leong Source Expert Review Removed was added to BBS2.
Rating Changed from Green List (high evidence) to No List (delete)
Polycystic liver disease v0.24 BBS12 Ivone Leong Source Expert Review Removed was added to BBS12.
Rating Changed from Green List (high evidence) to No List (delete)
Polycystic liver disease v0.24 BBS10 Ivone Leong Source Expert Review Removed was added to BBS10.
Rating Changed from Green List (high evidence) to No List (delete)
Polycystic liver disease v0.24 BBS1 Ivone Leong Source Expert Review Removed was added to BBS1.
Rating Changed from Green List (high evidence) to No List (delete)
Polycystic liver disease v0.24 B9D2 Ivone Leong Source Expert Review Removed was added to B9D2.
Rating Changed from Green List (high evidence) to No List (delete)
Polycystic liver disease v0.24 ARL6 Ivone Leong Source Expert Review Removed was added to ARL6.
Rating Changed from Green List (high evidence) to No List (delete)
Polycystic liver disease v0.24 AHI1 Ivone Leong Source Expert Review Removed was added to AHI1.
Rating Changed from Green List (high evidence) to No List (delete)
Genetic epilepsy syndromes v0.680 MFSD8 Sarah Leigh Publications for gene: MFSD8 were set to
Genetic epilepsy syndromes v0.679 ALG8 Sarah Leigh commented on gene: ALG8: Associated with Congenital disorder of glycosylation, type Ih 608104 in OMIM and as confirmed Gen2Phen, however, neither resource recorded seizures among the phenotypic features. Variants have been reported in at least 13 cases carrying biallelic ALG8 variants PMIDs 26066342 & 19688606.
Genetic epilepsy syndromes v0.679 ALG8 Sarah Leigh Classified gene: ALG8 as Green List (high evidence)
Genetic epilepsy syndromes v0.679 ALG8 Sarah Leigh Added comment: Comment on list classification: Based on evidence in publications 26066342 & 19688606
Genetic epilepsy syndromes v0.679 ALG8 Sarah Leigh Gene: alg8 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.678 ALG8 Sarah Leigh Phenotypes for gene: ALG8 were changed from to Congenital disorder of glycosylation, type Ih 608104
Genetic epilepsy syndromes v0.677 ALG8 Sarah Leigh Publications for gene: ALG8 were set to
Intellectual disability v2.530 DCPS Konstantinos Varvagiannis gene: DCPS was added
gene: DCPS was added to Intellectual disability. Sources: Expert Review,Literature
Mode of inheritance for gene: DCPS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DCPS were set to 25712129; 25701870; 30289615
Phenotypes for gene: DCPS were set to Al-Raqad syndrome (OMIM 616459)
Penetrance for gene: DCPS were set to Complete
Review for gene: DCPS was set to GREEN
gene: DCPS was marked as current diagnostic
Added comment: Biallelic pathogenic DCPS variants cause Al-Raqad syndrome (OMIM 616459).

7 patients from 3 families have been reported to date, all summarized in PMID 30289615 (first reports on the disorder - PMIDs : 25712129, 25701870).

Most individuals belong to consanguineous families although a compound heterozygous patient belonging to a broader consanguineous family (in PMID 25701870) and a further individual was born to unrelated parents originating from the same region (in PMID 30289615) have been described.

Overall, 2 splice site and 2 missense variants have been reported. Functional studies were carried out and support pathogenicity of the variants in the first 2 studies.

Developmental delay and intellectual disability are universal features.

DCPS is included in gene panels for intellectual disability offered by different diagnostic labs.

As a result this gene can be considered for inclusion in this panel as green.
Sources: Expert Review, Literature
Polycystic liver disease v0.23 Ivone Leong Panel status changed from public to internal
Intellectual disability v2.530 CHD3 Konstantinos Varvagiannis gene: CHD3 was added
gene: CHD3 was added to Intellectual disability. Sources: Expert Review,Literature
Mode of inheritance for gene: CHD3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CHD3 were set to 30397230
Phenotypes for gene: CHD3 were set to Global developmental delay; Intellectual disability; Macrocephaly
Penetrance for gene: CHD3 were set to unknown
Review for gene: CHD3 was set to GREEN
Added comment: PMID 30397230 is a collaborative study reporting on the phenotype of 35 individuals including 4 subjects from the DDD study, (most) with de novo mutations in CHD3.

Common features include developmental delay, variable degrees of intellectual disability, impaired speech and language (all 3 were universal features) as well as macrocephaly (in approximately 60%) or vision problems. Widely spaced eyes and high/broad/prominent forehead were among the most constant facial features (noted in around 80% each).

The majority of the variants reported are missense and cluster within the helicase domain although exceptions of missense variants in other domains or loss-of-function variants are provided. A few variants were recurrent and/or concerned the same residue.

Two pairs of affected siblings are reported, in one case this was explained by maternal mosaicism for the mutation.

Perturbed ATPase and/or chromatin remodeling activity relative to wild-type were demonstrated although both gain and loss of these activities were noted depending on the variant tested.

CHD3 is intolerant to both loss-of-function and missense variants (pLI of 1.0 and Z-score of +7.15).

As a result this gene can be considered for inclusion in the ID panel as green.
Sources: Expert Review, Literature
Genetic epilepsy syndromes v0.676 RHOBTB2 Konstantinos Varvagiannis gene: RHOBTB2 was added
gene: RHOBTB2 was added to Genetic Epilepsy Syndromes. Sources: Expert Review,Literature
Mode of inheritance for gene: RHOBTB2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RHOBTB2 were set to 29276004; 29768694; 26740508
Phenotypes for gene: RHOBTB2 were set to Global developmental delay; Intellectual disability; Seizures; Postnatal microcephaly
Penetrance for gene: RHOBTB2 were set to unknown
Mode of pathogenicity for gene: RHOBTB2 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: RHOBTB2 was set to GREEN
Added comment: PMID: 29276004 reports on 10 unrelated patients with de novo pathogenic missense variants in RHOBTB2. The phenotype in all individuals was compatible with a developmental and epileptic encephalopathy including early-onset seizures, severe intellectual disability, postnatal onset microcephaly (6/10) and movement disorders (8/10).

The variants occured as de novo events and clustered within the BTB-domain encoding region (within and between the 2 BTB domains). Three missense variants were recurrent and/or concerned the same residue (p.Arg483His in 4 individuals, Arg511Gln was reported in 2, and Arg511Trp was was found in another 2 individuals).

Functional studies in HEK293 cells suggested increased abundance of the mutant protein secondary to decreased proteasome degradation. Using Drosophila as a model organism, altered expression of RhoBTB (the single ortholog of the 3 vertebrate paralogs, closest to RHOBTB2) was shown to result in neurological phenotypes. RhoBTB overexpression in particular was associated with increased bang sensitivity (which was not the case or milder in the case if knockdown of this gene) and impaired performance upon the negative geotaxis assay, similar to the human neurological phenotypes. Altered RhoBTB dosage was shown to be associated with impaired dendrite development.

As commented by the authors, these results as well as the clustering of missense variants and the pLI score of 0.51 reported for RHOBTB2 are consistent with altered protein function (due to the missense variants) rather than haploinsufficiency or loss-of-function.

PMID: 29768694 describes 3 additional individuals, all found to harbor de novo missense variants again within the BTB-domain encoding region. Two of the variants had been reported in the previous study (Arg511Gln and Arg483His) while the third was a private one (Arg507Cys). The phenotype was similar to the previous descriptions. Functional studies were suggestive of impaired degradation of the mutant protein by the CUL3 complex although this was not secondary to decreased binding with CUL3.

PMID: 26740508 (cited by the two aforementioned publications) reports briefly on an individual with de novo missense variant in the same region of RHOBTB2 (Asn510Asp) and Rett-like phenotype.

RHOBTB2 is included in gene panels for intellectual disability offered by different diagnostic laboratories.

As a result the gene can be considered for inclusion in the intellectual disability and epilepsy panels as green.
Sources: Expert Review, Literature
Intellectual disability v2.530 RHOBTB2 Konstantinos Varvagiannis gene: RHOBTB2 was added
gene: RHOBTB2 was added to Intellectual disability. Sources: Expert Review,Literature
Mode of inheritance for gene: RHOBTB2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RHOBTB2 were set to 29276004; 29768694; 26740508
Phenotypes for gene: RHOBTB2 were set to Global developmental delay; Intellectual disability; Seizures; Postnatal microcephaly
Penetrance for gene: RHOBTB2 were set to unknown
Mode of pathogenicity for gene: RHOBTB2 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: RHOBTB2 was set to GREEN
gene: RHOBTB2 was marked as current diagnostic
Added comment: PMID: 29276004 reports on 10 unrelated patients with de novo pathogenic missense variants in RHOBTB2. The phenotype in all individuals was compatible with a developmental and epileptic encephalopathy including early-onset seizures, severe intellectual disability, postnatal onset microcephaly (6/10) and movement disorders (8/10).

The variants occured as de novo events and clustered within the BTB-domain encoding region (within and between the 2 BTB domains). Three missense variants were recurrent and/or concerned the same residue (p.Arg483His in 4 individuals, Arg511Gln was reported in 2, and Arg511Trp was was found in another 2 individuals).

Functional studies in HEK293 cells suggested increased abundance of the mutant protein secondary to decreased proteasome degradation. Using Drosophila as a model organism, altered expression of RhoBTB (the single ortholog of the 3 vertebrate paralogs, closest to RHOBTB2) was shown to result in neurological phenotypes. RhoBTB overexpression in particular was associated with increased bang sensitivity (which was not the case or milder in the case if knockdown of this gene) and impaired performance upon the negative geotaxis assay, similar to the human neurological phenotypes. Altered RhoBTB dosage was shown to be associated with impaired dendrite development.

As commented by the authors, these results as well as the clustering of missense variants and the pLI score of 0.51 reported for RHOBTB2 are consistent with altered protein function (due to the missense variants) rather than haploinsufficiency or loss-of-function.

PMID: 29768694 describes 3 additional individuals, all found to harbor de novo missense variants again within the BTB-domain encoding region. Two of the variants had been reported in the previous study (Arg511Gln and Arg483His) while the third was a private one (Arg507Cys). The phenotype was similar to the previous descriptions. Functional studies were suggestive of impaired degradation of the mutant protein by the CUL3 complex although this was not secondary to decreased binding with CUL3.

PMID: 26740508 (cited by the two aforementioned publications) reports briefly on an individual with de novo missense variant in the same region of RHOBTB2 (Asn510Asp) and Rett-like phenotype.

RHOBTB2 is included in gene panels for intellectual disability offered by different diagnostic laboratories.

As a result the gene can be considered for inclusion in the intellectual disability and epilepsy panels as green.
Sources: Expert Review, Literature
Polycystic liver disease v0.22 RSPH9 Ivone Leong Mode of inheritance for gene RSPH9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polycystic liver disease v0.21 RSPH4A Ivone Leong Source Expert list was added to RSPH4A.
Mode of inheritance for gene RSPH4A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.676 CACNA1A Sarah Leigh Marked gene: CACNA1A as ready
Genetic epilepsy syndromes v0.676 CACNA1A Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 3 variants reported in 4 unrelated cases.
Genetic epilepsy syndromes v0.676 CACNA1A Sarah Leigh Gene: cacna1a has been classified as Green List (High Evidence).
Polycystic liver disease v0.20 SEC61B Ivone Leong Phenotypes for gene: SEC61B were changed from Association with polycystic liver disease 1 with or without renal cysts (VUS) (174050) to Association with polycystic liver disease 1 with or without renal cysts
Polycystic liver disease v0.19 ALG8 Ivone Leong Mode of inheritance for gene ALG8 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: ALG8 were changed from Polycystic Liver Disease 3 (617874) to Polycystic Liver Disease 3 (617874); Congenital disorder of glycosylation, type Ih (608104)
Polycystic liver disease v0.18 CCDC40 Ivone Leong Mode of inheritance for gene CCDC40 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.676 RANBP2 Sarah Leigh Phenotypes for gene: RANBP2 were changed from {Encephalopathy, acute, infection-induced, 3, susceptibility to} to {Encephalopathy, acute, infection-induced, 3, susceptibility to} 608033
Polycystic liver disease v0.17 CCDC39 Ivone Leong Mode of inheritance for gene CCDC39 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.675 MAPK10 Sarah Leigh Marked gene: MAPK10 as ready
Genetic epilepsy syndromes v0.675 MAPK10 Sarah Leigh Added comment: Comment when marking as ready: The the variant RCV000007138 has been reclassified in OMIM to a variant of unknown significance due to lack of evidence for the gene disease association.
Genetic epilepsy syndromes v0.675 MAPK10 Sarah Leigh Gene: mapk10 has been classified as Red List (Low Evidence).
Genetic epilepsy syndromes v0.675 MAPK10 Sarah Leigh Classified gene: MAPK10 as Red List (low evidence)
Genetic epilepsy syndromes v0.675 MAPK10 Sarah Leigh Gene: mapk10 has been classified as Red List (Low Evidence).
Genetic epilepsy syndromes v0.674 MAPK10 Sarah Leigh Publications for gene: MAPK10 were set to PMID: 23329067
Genetic epilepsy syndromes v0.673 CHD2 Sarah Leigh Phenotypes for gene: CHD2 were changed from EPILEPTIC ENCEPHALOPATHY to Epileptic encephalopathy, childhood-onset 615369
Genetic epilepsy syndromes v0.672 ARX Sarah Leigh Phenotypes for gene: ARX were changed from to Epileptic encephalopathy, early infantile, 1 308350; Hydranencephaly with abnormal genitalia 300215; Lissencephaly, X-linked 2 300215; Mental retardation, X-linked 29 and others 300419; Partington syndrome 309510; Proud syndrome 300004
Genetic epilepsy syndromes v0.671 ARHGEF9 Sarah Leigh Phenotypes for gene: ARHGEF9 were changed from to Epileptic encephalopathy, early infantile, 8 300607
Genetic epilepsy syndromes v0.670 ALDH7A1 Sarah Leigh Phenotypes for gene: ALDH7A1 were changed from to Epilepsy, pyridoxine-dependent 266100
Genetic epilepsy syndromes v0.669 PIK3R2 Sarah Leigh Mode of inheritance for gene: PIK3R2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic epilepsy syndromes v0.668 SMARCA2 Sarah Leigh Marked gene: SMARCA2 as ready
Genetic epilepsy syndromes v0.668 SMARCA2 Sarah Leigh Gene: smarca2 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.668 SMARCA2 Sarah Leigh Classified gene: SMARCA2 as Green List (high evidence)
Genetic epilepsy syndromes v0.668 SMARCA2 Sarah Leigh Gene: smarca2 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.667 SMARCA2 Sarah Leigh gene: SMARCA2 was added
gene: SMARCA2 was added to Genetic Epilepsy Syndromes. Sources: Expert list
Mode of inheritance for gene: SMARCA2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SMARCA2 were set to 22366787
Phenotypes for gene: SMARCA2 were set to Nicolaides-Baraitser syndrome 601358
Review for gene: SMARCA2 was set to GREEN
Added comment: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. In PMID 22366787 22/35 Nicolaides-Baraitser syndrome cases with SMARCA2 variant had seizures as part of their phenotype.
Gene provided by Ian Berry, Leeds
Sources: Expert list
Genetic epilepsy syndromes v0.666 CREBBP Sarah Leigh Classified gene: CREBBP as Green List (high evidence)
Genetic epilepsy syndromes v0.666 CREBBP Sarah Leigh Gene: crebbp has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.665 CREBBP Sarah Leigh Publications for gene: CREBBP were set to 20684013
Genetic epilepsy syndromes v0.664 CREBBP Sarah Leigh Marked gene: CREBBP as ready
Genetic epilepsy syndromes v0.664 CREBBP Sarah Leigh Gene: crebbp has been classified as Red List (Low Evidence).
Genetic epilepsy syndromes v0.664 CREBBP Sarah Leigh gene: CREBBP was added
gene: CREBBP was added to Genetic Epilepsy Syndromes. Sources: Expert list
Mode of inheritance for gene: CREBBP was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CREBBP were set to 20684013
Phenotypes for gene: CREBBP were set to Rubinstein-Taybi syndrome 1 180849
Review for gene: CREBBP was set to RED
Added comment: Associated with Rubinstein-Taybi syndrome 1 in OMIM and as confirmed Gen2Phen gene for this phenotype. Although seizures are reported as a feature of Rubinstein-Taybi syndrome 1, seizures were only recorded in a single 2 year old girl who had several complex focal seizures, a year later a slow growing ganglioglioma of the brain (left temporo–medio–basal region) was surgically removed, after which the seizures ceased (PMID 20684013).
Sources: Expert list
Genetic epilepsy syndromes v0.663 SLC6A5 Sarah Leigh Marked gene: SLC6A5 as ready
Genetic epilepsy syndromes v0.663 SLC6A5 Sarah Leigh Added comment: Comment when marking as ready: The phenotype Hyperekplexia 3, 614618 includes exaggerated startle response to tactile or acoustic stimuli, manifesting as non-epileptic seizures. This phenotype is therefore not relevant to the Genetic epilepsy syndromes panel.
Genetic epilepsy syndromes v0.663 SLC6A5 Sarah Leigh Gene: slc6a5 has been classified as Red List (Low Evidence).
Genetic epilepsy syndromes v0.663 SLC6A5 Sarah Leigh Phenotypes for gene: SLC6A5 were changed from to Hyperekplexia 3, 614618
Genetic epilepsy syndromes v0.662 SLC6A5 Sarah Leigh Mode of inheritance for gene: SLC6A5 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Non-syndromic familial congenital anorectal malformations v1.0 Eleanor Williams promoted panel to version 1.0
Genetic epilepsy syndromes v0.661 RYR3 Sarah Leigh Marked gene: RYR3 as ready
Genetic epilepsy syndromes v0.661 RYR3 Sarah Leigh Added comment: Comment when marking as ready: Not associated with phenotype in OMIM (lasted edited 01/25/2005) or in Gen2Phen. Four variants reported in four cases, but with little supportive evidence for association with Epileptic encephalopathy.
Genetic epilepsy syndromes v0.661 RYR3 Sarah Leigh Gene: ryr3 has been classified as Red List (Low Evidence).
Non-syndromic familial congenital anorectal malformations v0.120 CASK Eleanor Williams Publications for gene: CASK were set to 19200522; 28139025; 20029458; 25886057
Non-syndromic familial congenital anorectal malformations v0.119 CASK Eleanor Williams Tag watchlist tag was added to gene: CASK.
Non-syndromic familial congenital anorectal malformations v0.119 CDX2 Eleanor Williams Tag watchlist tag was added to gene: CDX2.
Non-syndromic familial congenital anorectal malformations v0.119 MYCN Eleanor Williams Tag watchlist tag was added to gene: MYCN.
Non-syndromic familial congenital anorectal malformations v0.119 MYH14 Eleanor Williams Tag watchlist tag was added to gene: MYH14.
Genetic epilepsy syndromes v0.661 RYR3 Sarah Leigh Added comment: Comment on mode of inheritance: MOI based on report in PMID 29667327
Genetic epilepsy syndromes v0.661 RYR3 Sarah Leigh Mode of inheritance for gene: RYR3 was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.660 RYR3 Sarah Leigh Phenotypes for gene: RYR3 were changed from to Epileptic encephalopathy
Genetic epilepsy syndromes v0.659 RYR3 Sarah Leigh Publications for gene: RYR3 were set to 25262651
Genetic epilepsy syndromes v0.658 RYR2 Sarah Leigh Publications for gene: RYR2 were set to 27832686; 18483626; 29667327; 11208676; 12093772; 11157710
Genetic epilepsy syndromes v0.657 RYR2 Sarah Leigh Classified gene: RYR2 as Amber List (moderate evidence)
Genetic epilepsy syndromes v0.657 RYR2 Sarah Leigh Gene: ryr2 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v0.656 RYR2 Sarah Leigh gene: RYR2 was added
gene: RYR2 was added to Genetic Epilepsy Syndromes. Sources: Literature
Mode of inheritance for gene: RYR2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RYR2 were set to 27832686; 18483626; 29667327; 11208676; 12093772; 11157710
Phenotypes for gene: RYR2 were set to Ventricular tachycardia, catecholaminergic polymorphic, 1 604772
Review for gene: RYR2 was set to AMBER
Added comment: Associated with phenotype in OMIM and not in Gen2Phen. At least 3 variants identified in cases displaying seizures (PMIDs 29667327 & 18483626), together with a mouse model (PMID 27832686). However, there are numerous cases of Ventricular tachycardia, catecholaminergic polymorphic, 1 604772, with no reports of seizures (PMIDs 11208676, 12093772, 11157710), therefore seizures appear to be a rare feature of this condition.
Sources: Literature
Genetic epilepsy syndromes v0.655 RNASEH2A Rebecca Foulger Marked gene: RNASEH2A as ready
Genetic epilepsy syndromes v0.655 RNASEH2A Rebecca Foulger Gene: rnaseh2a has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.655 RNASEH2A Rebecca Foulger Classified gene: RNASEH2A as Green List (high evidence)
Genetic epilepsy syndromes v0.655 RNASEH2A Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green. Green Review plus Confirmed DD-G2P gene for Aicardi-Goutieres syndrome 4, which can present with seizures. Seizures is a common (at least 50%) feature of patients with AGS. Although it's hard to trace in papers whether the AGS patients specifically with RNASEH2A variants displayed seizures, RNASEH2A variants are a known cause of AGS, and seizures are a common feature of AGS; therefore it is reasonable to include RNASEH2A on the Genetic Epilepsy panel.
Genetic epilepsy syndromes v0.655 RNASEH2A Rebecca Foulger Gene: rnaseh2a has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.654 RNASEH2A Rebecca Foulger Publications for gene: RNASEH2A were set to
Genetic epilepsy syndromes v0.653 RNASEH2A Rebecca Foulger Mode of inheritance for gene: RNASEH2A was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.652 RNASEH2A Rebecca Foulger commented on gene: RNASEH2A: Crow et al., 2015 (PMID:25604658) report data for 374 mutation-positive patients from 299 families encompassing all seven known AGS-related genes. 140 of 362 patients had seizures. Biallelic RNASEH2A variants were reported in 14 families.
Genetic epilepsy syndromes v0.652 RNASEH2A Rebecca Foulger commented on gene: RNASEH2A: Rice et al 2007 (PMID:17846997) collected clinical data for 123 individuals from 94 families with variants in TREX1, RNASEH2A, RNASEH2B, or RNASEH2C. Seizures were reported in 53% of patients. 4 children from 3 families had biallelic variants in RNASEH2A. 1 individual with RNASEH2A variant who was affected at birth experienced neonatal seizures (Table 2).
Genetic epilepsy syndromes v0.652 RNASEH2A Rebecca Foulger commented on gene: RNASEH2A
Genetic epilepsy syndromes v0.652 RNASEH2A Rebecca Foulger Phenotypes for gene: RNASEH2A were changed from to Aicardi-Goutieres syndrome 4, 610333
Genetic epilepsy syndromes v0.651 TBL1XR1 Rebecca Foulger Marked gene: TBL1XR1 as ready
Genetic epilepsy syndromes v0.651 TBL1XR1 Rebecca Foulger Gene: tbl1xr1 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.651 TBL1XR1 Rebecca Foulger Classified gene: TBL1XR1 as Green List (high evidence)
Genetic epilepsy syndromes v0.651 TBL1XR1 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green: Confirmed DD-G2P gene for Pierpont and mental retardation, both of which can present with seizures. Seizures reported in at least 3 patients (PMID:25102098, PMID:30365874 and PMID:9450851-original patient). Burkitt Wright, 2011 (PMID:21834056) also reports that "Seizures, in particular absence seizures, have been reported in several [Pierpont] patients. While they are clearly not universal, it currently appears that epilepsy may be sufficiently more common in children with Pierpont syndrome to be considered a feature of the condition". Therefore reasonable to include TBL1XR1 on the diagnostic panel.
Genetic epilepsy syndromes v0.651 TBL1XR1 Rebecca Foulger Gene: tbl1xr1 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.650 TBL1XR1 Rebecca Foulger Publications for gene: TBL1XR1 were set to
Genetic epilepsy syndromes v0.649 TBL1XR1 Rebecca Foulger Mode of inheritance for gene: TBL1XR1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic epilepsy syndromes v0.648 TBL1XR1 Rebecca Foulger Phenotypes for gene: TBL1XR1 were changed from to Mental retardation, autosomal dominant 41, 616944; Pierpont syndrome, 602342
Arthrogryposis - broad panel v0.1 Ellen McDonagh Changed child panels to: Arthrogryposis
Arthrogryposis - broad panel v0.0 Ellen McDonagh Added Panel Arthrogryposis - broad panel
Set panel types to: Super Panel; GMS Rare Disease Virtual
Genetic epilepsy syndromes v0.647 TBL1XR1 Rebecca Foulger commented on gene: TBL1XR1: Previously reported individuals reported by Burkitt Wright, 2011 (PMID:21834056) include the initial patient reported by Pierpont et al 1998 (PMID:9450851) who had grand mal seizures from age 5.
Genetic epilepsy syndromes v0.647 TBL1XR1 Rebecca Foulger commented on gene: TBL1XR1: PMID:30365874 (Lemattre et al 2018) report a Caucasian boy (Patient 1) with a seizure disorder with both myoclonic and focal seizures that began age 10. Her harboured a de novo heterozygous missense variant (NM_024665.4:c.974G>A, p.Cys325Tyr) in TBL1XR1. Their second unrelated patient also had a missense TBL1XR1 variant but never had seizures.
Genetic epilepsy syndromes v0.647 TBL1XR1 Rebecca Foulger commented on gene: TBL1XR1: In a 5-year-old Japanese girl with autosomal dominant mental retardation-41 (MRD41; 616944), Saitsu et al. (2014, PMID:25102098) identified a de novo heterozygous transition (c.209G-A, NM_024665.4) in the TBL1XR1 gene (G70D). The patient developed infantile spasms at age 5 months.
Genetic epilepsy syndromes v0.647 TBL1XR1 Rebecca Foulger commented on gene: TBL1XR1
Genetic epilepsy syndromes v0.647 TIMM50 Rebecca Foulger Marked gene: TIMM50 as ready
Genetic epilepsy syndromes v0.647 TIMM50 Rebecca Foulger Gene: timm50 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v0.647 TIMM50 Rebecca Foulger Classified gene: TIMM50 as Amber List (moderate evidence)
Genetic epilepsy syndromes v0.647 TIMM50 Rebecca Foulger Added comment: Comment on list classification: Kept rating as Amber: 2 families reported in PMID:27573165 plus 1 family reported in a conference abstract. Further published or clinical cases required for diagnostic rating.
Genetic epilepsy syndromes v0.647 TIMM50 Rebecca Foulger Gene: timm50 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v0.646 TIMM50 Rebecca Foulger Publications for gene: TIMM50 were set to 27573165
Genetic epilepsy syndromes v0.645 TIMM50 Rebecca Foulger commented on gene: TIMM50: In a conference abstract, Serajee et al identified a homozygous mutation, Gly372Ser, in the TIMM50 gene, in three sibs who suffered from intractable epilepsy and developmental delay accompanied by 3-methylglutaconic aciduria.
Genetic epilepsy syndromes v0.645 TIMM50 Rebecca Foulger Mode of inheritance for gene: TIMM50 was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.644 TIMM50 Rebecca Foulger commented on gene: TIMM50
Genetic epilepsy syndromes v0.644 TIMM50 Rebecca Foulger Publications for gene: TIMM50 were set to
Genetic epilepsy syndromes v0.643 TIMM50 Rebecca Foulger Phenotypes for gene: TIMM50 were changed from to 3-methylglutaconic aciduria, type IX, 617698; intellectual disability and seizure; epilepsy and developmental delay
Genetic epilepsy syndromes v0.642 TMEM70 Rebecca Foulger Marked gene: TMEM70 as ready
Genetic epilepsy syndromes v0.642 TMEM70 Rebecca Foulger Gene: tmem70 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.642 TMEM70 Rebecca Foulger Publications for gene: TMEM70 were set to
Genetic epilepsy syndromes v0.641 TMEM70 Rebecca Foulger Classified gene: TMEM70 as Green List (high evidence)
Genetic epilepsy syndromes v0.641 TMEM70 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green: Green review, and Confirmed DD-G2P gene for Mitochondrial complex V (ATP synthase) deficiency, nuclear type 2, 614052 which can present with seizures. Seizures reported in 3 unrelated patients from the literature (2 in PMID:18953340 and 1 in PMID:21147908) so just sufficient cases for Green rating.
Genetic epilepsy syndromes v0.641 TMEM70 Rebecca Foulger Gene: tmem70 has been classified as Green List (High Evidence).
Genetic epilepsy syndromes v0.640 TMEM70 Rebecca Foulger Mode of inheritance for gene: TMEM70 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.639 TMEM70 Rebecca Foulger Mode of inheritance for gene: TMEM70 was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.638 RYR3 Sarah Leigh Publications for gene: RYR3 were set to EuroEPINOMICS-RES Consortium (2014) AJHG 95:1-11
Genetic epilepsy syndromes v0.637 TMEM70 Rebecca Foulger Phenotypes for gene: TMEM70 were changed from to Mitochondrial complex V (ATP synthase) deficiency, nuclear type 2, 614052; seizures
Genetic epilepsy syndromes v0.636 TMEM70 Rebecca Foulger commented on gene: TMEM70: In 6 patients from 4 unrelated consanguineous Arab-Muslim families with MC5DN2, Spiegel et al. (2011, PMID:21147908) identified 4 different homozygous mutations in the TMEM70 gene. Patient IV-1 developed generalised seizures at age 13.
Genetic epilepsy syndromes v0.636 TMEM70 Rebecca Foulger commented on gene: TMEM70
Genetic epilepsy syndromes v0.636 TNK2 Rebecca Foulger Marked gene: TNK2 as ready
Genetic epilepsy syndromes v0.636 TNK2 Rebecca Foulger Gene: tnk2 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v0.636 TNK2 Rebecca Foulger commented on gene: TNK2: Added 'watchlist' tag.
Genetic epilepsy syndromes v0.636 TNK2 Rebecca Foulger Tag watchlist tag was added to gene: TNK2.
Genetic epilepsy syndromes v0.636 TNK2 Rebecca Foulger Classified gene: TNK2 as Amber List (moderate evidence)
Genetic epilepsy syndromes v0.636 TNK2 Rebecca Foulger Added comment: Comment on list classification: Kept rating as Amber: 3 unrelated families reported in total: 3 siblings from PMID:23686771, and 2 further cases from PMID:27977884. However, the V716M variant from PMID:23686771 is classed as VUS in OMIM. And little information is given about the compound het variants from PMID:27977884. Therefore Amber rating awaiting further cases.
Genetic epilepsy syndromes v0.636 TNK2 Rebecca Foulger Gene: tnk2 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v0.635 TNK2 Rebecca Foulger Mode of inheritance for gene: TNK2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.634 TNK2 Rebecca Foulger Phenotypes for gene: TNK2 were changed from to severe autosomal recessive infantile onset epilepsy; EE
Genetic epilepsy syndromes v0.633 TNK2 Rebecca Foulger Publications for gene: TNK2 were set to
Genetic epilepsy syndromes v0.632 TNK2 Rebecca Foulger commented on gene: TNK2: PMID:27977884 (Mao et al. 2017) report 2 further seizure patients with TNK2 variants. Patient A is a 20 month old non-dysmorphic girl of healthy non-consanguineous parents. At 13 months of age, she started to have spasm seizures. A pair of compound heterozygote variants in TNK2 (c.2860 G>T, c.3004 G>T) was found and verified by Sanger sequencing. Patient B is an 18 month old girl and the 2nd of 3 children of healthy parents. At the age of 11 months she exhibited seizure activity characterized by cluster of spasm. Sequencing found a pair of compound heterozygote variants in TNK2 (c.1705 A>G, c.2243 G>A) which were verified by Sanger sequencing. No further information on the variants (including protein information) was given.
Genetic epilepsy syndromes v0.632 TNK2 Rebecca Foulger commented on gene: TNK2
Genetic epilepsy syndromes v0.632 TRAPPC12 Rebecca Foulger Marked gene: TRAPPC12 as ready
Genetic epilepsy syndromes v0.632 TRAPPC12 Rebecca Foulger Gene: trappc12 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v0.632 TRAPPC12 Rebecca Foulger Classified gene: TRAPPC12 as Amber List (moderate evidence)
Genetic epilepsy syndromes v0.632 TRAPPC12 Rebecca Foulger Added comment: Comment on list classification: Kept rating as Amber: 2 literature cases only in PMID:28777934. Seizures are a phenotype of both cases but further cases required for a diagnostic rating.
Genetic epilepsy syndromes v0.632 TRAPPC12 Rebecca Foulger Gene: trappc12 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v0.631 TRAPPC12 Rebecca Foulger Deleted their comment
Genetic epilepsy syndromes v0.631 TRAPPC12 Rebecca Foulger Classified gene: TRAPPC12 as Amber List (moderate evidence)
Genetic epilepsy syndromes v0.631 TRAPPC12 Rebecca Foulger Added comment: Comment on list classification: In 3 patients from 2 unrelated families with early-onset progressive encephalopathy with brain atrophy and spasticity (MIM:617669), Milev et al. (2017, PMID:28777934) identified homozygous or compound heterozygous mutations in the TRAPPC12 gene. The article text reports seizures in all 3 patients.
Genetic epilepsy syndromes v0.631 TRAPPC12 Rebecca Foulger Gene: trappc12 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v0.630 TRAPPC12 Rebecca Foulger commented on gene: TRAPPC12
Genetic epilepsy syndromes v0.630 TRAPPC12 Rebecca Foulger Publications for gene: TRAPPC12 were set to
Genetic epilepsy syndromes v0.629 TRAPPC12 Rebecca Foulger Phenotypes for gene: TRAPPC12 were changed from to Encephalopathy, progressive, early-onset, with brain atrophy and spasticity, 617669
Genetic epilepsy syndromes v0.628 TRAPPC12 Rebecca Foulger Mode of inheritance for gene: TRAPPC12 was changed from to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v0.627 TRAPPC6B Rebecca Foulger Marked gene: TRAPPC6B as ready