ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.2767A>G (p.Ile923Val)

dbSNP: rs2105807305
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001763578 SCV001997852 uncertain significance not provided 2019-10-10 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); The majority of missense variants in this gene are considered pathogenic [(Stenson et al., 2014; other references)]; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this 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 within the extracellular loop between the S5 and S6 transmembrane segments of the second homologous domain
Labcorp Genetics (formerly Invitae), Labcorp RCV005094992 SCV005815195 uncertain significance Early infantile epileptic encephalopathy with suppression bursts 2024-11-19 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 923 of the SCN1A protein (p.Ile923Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SCN1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 1309067). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt SCN1A protein function with a positive predictive value of 95%. 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.

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