ClinVar Miner

Submissions for variant NM_006514.4(SCN10A):c.1492C>T (p.Arg498Trp)

gnomAD frequency: 0.00005  dbSNP: rs377467259
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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 RCV001048985 SCV001213015 uncertain significance Brugada syndrome 2022-09-01 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with SCN10A-related conditions. This variant is present in population databases (rs377467259, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 498 of the SCN10A protein (p.Arg498Trp). ClinVar contains an entry for this variant (Variation ID: 845838). 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. 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.
Ambry Genetics RCV002393241 SCV002700075 likely benign Cardiovascular phenotype 2020-10-30 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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