ClinVar Miner

Submissions for variant NM_006514.4(SCN10A):c.1004A>G (p.Asn335Ser)

gnomAD frequency: 0.00001  dbSNP: rs966272776
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000489557 SCV000576721 uncertain significance not provided 2017-04-20 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the SCN10A gene. The N335S variant has not been published as pathogenic or been reported as benign to our knowledge. Additionally, this variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). However, the N335S variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Furthermore, this substitution occurs at a position that is not conserved across species and in silico analysis predicts this variant likely does not alter the protein structure/function.
Labcorp Genetics (formerly Invitae), Labcorp RCV005056066 SCV005705673 uncertain significance Brugada syndrome 2024-11-10 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 335 of the SCN10A protein (p.Asn335Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SCN10A-related conditions. ClinVar contains an entry for this variant (Variation ID: 426312). 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 SCN10A protein function with a negative predictive value of 80%. 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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