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

dbSNP: rs794726799

Total submissions: 9

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	2020-07-07	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 in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 25525159, 17054684, 27465585, 30182498, 30321769, 26096185, 31009440, 30868114, 23808377, 30641252, 32090326, 33278787, 31031587)
Invitae	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