ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.1129C>T (p.Arg377Ter)

dbSNP: rs794726799
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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 RCV000180917 SCV000221893 pathogenic Severe myoclonic epilepsy in infancy 2014-12-20 criteria provided, single submitter research
GeneDx RCV000423099 SCV000514487 pathogenic not provided 2024-08-08 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 17054684, 27465585, 30182498, 30321769, 26096185, 31009440, 30868114, 23808377, 30641252, 32090326, 33278787, 32427350, 31440721, 31031587, 28664031, 35074891, 36480001, 36801247)
Labcorp Genetics (formerly Invitae), Labcorp RCV000529401 SCV000633808 pathogenic Early infantile epileptic encephalopathy with suppression bursts 2023-10-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg377*) in the SCN1A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SCN1A are known to be pathogenic (PMID: 17347258, 18930999). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Dravet syndrome (PMID: 17054684, 23808377, 27465585). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 189963). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen RCV000423099 SCV001501315 pathogenic not provided 2020-07-01 criteria provided, single submitter clinical testing
Neuberg Centre For Genomic Medicine, NCGM RCV000180917 SCV002820213 pathogenic Severe myoclonic epilepsy in infancy criteria provided, single submitter clinical testing The stop gained variant c.1129C>T(p.Arg377Ter) in SCN1A gene has been reported previously in individuals affected with Dravet syndrome (Djémié et al., 2016). This variant has been reported to the ClinVar database as Pathogenic. The p.Arg377Ter variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. The nucleotide change in SCN1A is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. This variant is predicted to cause loss of normal protein function through protein truncation. Loss-of-function variants in SCN1A are known to be pathogenic (Harkin et al., 2007; Depienne et al., 2009). For these reasons, this variant has been classified as Pathogenic.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000423099 SCV001742868 pathogenic not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000423099 SCV001953968 pathogenic not provided no assertion criteria provided clinical testing
Génétique des Maladies du Développement, Hospices Civils de Lyon RCV000180917 SCV002538990 pathogenic Severe myoclonic epilepsy in infancy no assertion criteria provided clinical testing
Diagnostic Laboratory, Strasbourg University Hospital RCV002274946 SCV002562850 likely pathogenic Seizure no assertion criteria provided clinical testing

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