Submissions for variant NM_001165963.4(SCN1A):c.1712G>A (p.Arg571Lys)

dbSNP: rs1697493699

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001763758	SCV002001164	uncertain significance	not provided	2020-06-22	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (Lek et al., 2016); Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This substitution is predicted to be in the cytoplasmic loop between the first and second homologous domains; Missense variants in nearby residues reported in the Human Gene Mutation Database (Stenson et al., 2014)
Labcorp Genetics (formerly Invitae), Labcorp	RCV002539160	SCV003523724	uncertain significance	Early infantile epileptic encephalopathy with suppression bursts	2023-06-27	criteria provided, single submitter	clinical testing	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SCN1A protein function. ClinVar contains an entry for this variant (Variation ID: 1312752). This variant has not been reported in the literature in individuals affected with SCN1A-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 571 of the SCN1A protein (p.Arg571Lys).