ClinVar Miner

Submissions for variant NM_006514.4(SCN10A):c.2221C>G (p.Leu741Val)

gnomAD frequency: 0.00002  dbSNP: rs137906740
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001350750 SCV001545167 uncertain significance Brugada syndrome 2025-01-28 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 741 of the SCN10A protein (p.Leu741Val). This variant is present in population databases (rs137906740, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of erythromelalgia (PMID: 29911575, 30554136). ClinVar contains an entry for this variant (Variation ID: 1046224). 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.
Fulgent Genetics, Fulgent Genetics RCV002486446 SCV002776846 uncertain significance Episodic pain syndrome, familial, 2 2021-07-20 criteria provided, single submitter clinical testing
Ambry Genetics RCV003169738 SCV003860557 likely benign Cardiovascular phenotype 2023-01-31 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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