ClinVar Miner

Submissions for variant NM_006920.6(SCN1A):c.4265G>A (p.Gly1422Glu) (rs121918741)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Bioinformatics, Peking University RCV000059509 SCV000221756 pathogenic Severe myoclonic epilepsy in infancy 2014-12-20 criteria provided, single submitter research
GeneDx RCV000521069 SCV000617432 pathogenic not provided 2017-06-22 criteria provided, single submitter clinical testing An G1433E published pathogenic variant has been identified in the SCN1A gene. The G1433E variant has been reported previously as a de novo pathogenic variant in patients with a clinical diagnosis of Dravet syndrome (Verbeek et al., 2013; Sun et al., 2008; SCN1A Variant Database). Additionally, a different missense substitution at the same codon (G1433R) as well as multiple missense variants in nearby residues have been reported in the Human Gene Mutation Database in association with SCN1A-related disorders ((Nicita et al., 2010; Stenson et al., 2014), supporting the functional importance of this region of the protein. G1433E alters a highly conserved position predicted to be within the pore forming loop between the S5 and S6 transmembrane segments of the third homologous domain,. The G1433E variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Furthermore, the G1433E variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties and in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, the presence of G1433E is consistent with the diagnosis of an SCN1A-related disorder in this individual.
UniProtKB/Swiss-Prot RCV000059509 SCV000091035 not provided Severe myoclonic epilepsy in infancy no assertion provided not provided

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