ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.5348C>T (p.Ala1783Val) (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).
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000189000 SCV000341355 pathogenic not provided 2016-06-02 criteria provided, single submitter clinical testing
Invitae RCV001207693 SCV001379057 pathogenic Early infantile epileptic encephalopathy 2019-10-24 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 variant has been observed in individual(s) with Dravet syndrome (PMID: 18930999, 29460957, 17561957). 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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