ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.5348C>T (p.Ala1783Val)

dbSNP: rs121917921
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Bioinformatics, Peking University RCV000059446 SCV000221927 pathogenic Severe myoclonic epilepsy in infancy 2014-12-20 criteria provided, single submitter research
GeneDx RCV000189000 SCV000242631 pathogenic not provided 2014-03-12 criteria provided, single submitter clinical testing p.Ala1783Val (GCG>GTG): c.5348 C>T in exon 26 of the SCN1A gene (NM_001165963.1) The Ala1783Val variant has been previously reported as a de novo mutation in multiple unrelated patients with Dravet syndrome (Marini et al., 2007; Depienne et al., 2009). This substitution occurs at a position that is highly conserved across species and is located in transmembrane segment S6 in the fourth homologous domain. Therefore, Ala1783Val is considered a disease-causing mutation. The variant is found in INFANT-EPI panel(s).
Eurofins NTD LLC (GA) RCV000189000 SCV000341355 pathogenic not provided 2016-06-02 criteria provided, single submitter clinical testing
Invitae RCV001207693 SCV001379057 pathogenic Early infantile epileptic encephalopathy with suppression bursts 2021-09-02 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 1783 of the SCN1A protein (p.Ala1783Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with Dravet syndrome (PMID: 17561957, 18930999, 29460957). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 68571). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. For these reasons, this variant has been classified as Pathogenic.
UniProtKB/Swiss-Prot RCV000059446 SCV000090971 not provided Severe myoclonic epilepsy in infancy no assertion provided not provided

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