ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.1049T>A (p.Met350Lys)

dbSNP: rs1283627130
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000795921 SCV000935402 uncertain significance Early infantile epileptic encephalopathy with suppression bursts 2025-01-15 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with lysine, which is basic and polar, at codon 350 of the SCN1A protein (p.Met350Lys). 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: 642450). 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 not expected to disrupt SCN1A protein function with a negative 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.
GeneDx RCV004760796 SCV005369887 uncertain significance not provided 2023-06-08 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant does not alter protein structure/function; This substitution is predicted to be within the extracellular loop between the S5 and S6 transmembrane segments of the first homologous domain; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 31257224, 29127303)

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