ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.2134C>T (p.Arg712Ter) (rs794726730)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Bioinformatics, Peking University RCV000174291 SCV000221803 pathogenic Severe myoclonic epilepsy in infancy 2014-12-20 criteria provided, single submitter research
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000188886 SCV000225570 pathogenic not provided 2014-07-31 criteria provided, single submitter clinical testing
GeneDx RCV000188886 SCV000242516 pathogenic not provided 2018-06-22 criteria provided, single submitter clinical testing The R712X nonsense variant in the SCN1A gene is a recurrent pathogenic variant that has been identified in multiple unrelated patients with Dravet syndrome (Sugawara et al., 2002; Depienne et al., 2009; SCN1A Variant Database). This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation ornonsense-mediated mRNA decay. The R712X variant is not observed in large population cohorts (Lek et al., 2016). Therefore, the presence of R712X is consistent with the diagnosis of an SCN1A-related disorder in this individual.
Athena Diagnostics Inc RCV000174291 SCV000255815 pathogenic Severe myoclonic epilepsy in infancy 2014-04-30 criteria provided, single submitter clinical testing
Invitae RCV000534243 SCV000633820 pathogenic Early infantile epileptic encephalopathy with suppression bursts 2017-07-14 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg712*) in the SCN1A gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported to be de novo in individuals affected with Dravet syndrome (PMID: 11940708, 23808377, 23195492, 26533041).  This is common SCN1A variant reported in individuals with epileptic encephalopathy (PMID: 12083760, 18804930). ClinVar contains an entry for this variant (Variation ID: 189886). Loss-of-function variants in SCN1A are known to be pathogenic (PMID: 17347258, 18930999). For these reasons, this variant has been classified as Pathogenic.
Génétique des Maladies du Développement, Hospices Civils de Lyon RCV001004670 SCV001164121 pathogenic Generalized epilepsy with febrile seizures plus, type 2 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000188886 SCV001248488 pathogenic not provided 2021-05-01 criteria provided, single submitter clinical testing
LifeCell International Pvt. Ltd RCV001004670 SCV001739363 pathogenic Generalized epilepsy with febrile seizures plus, type 2 criteria provided, single submitter clinical testing A heterozygous nonsense variation in exon 15 of the SCN1A gene (c.2134C>T) that results in a stop codon and premature truncation of the protein at codon 712 (p.Arg712Ter) was detected. The observed variant is not present in both the 1000 Genomes and gnomAD databases. The reference base is conserved across the species and in-silico predictions by CADD is damaging. The gene SCN1A has a low rate of benign loss of function variants as indicated by a high LoF variants Z-Score of 8.42. This variant is predicted to cause loss of normal protein function through protein truncation.This variant has previously been reported for early infantile epileptic encephalopathy by Arafat A et al., 2017. This variant was found in ClinVar (Variant 189886) with a classification of Pathogenic with respect to Early infantile epileptic encephalopathy with suppression bursts and a review status of (2 stars) no assertion criteria provided (https://www.ncbi.nlm.nih.gov/clinvar/variation/189886/). Based on the above evidence this variant has been classified as pathogenic according to the ACMG guidelines.
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille RCV001527645 SCV001738757 pathogenic Epileptic encephalopathy, early infantile, 1 2020-01-01 no assertion criteria provided clinical testing

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