ClinVar Miner

Submissions for variant NM_006514.4(SCN10A):c.2282T>C (p.Leu761Pro)

gnomAD frequency: 0.00003  dbSNP: rs139988577
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001960980 SCV002245077 uncertain significance Brugada syndrome 2022-07-18 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 761 of the SCN10A protein (p.Leu761Pro). This variant is present in population databases (rs139988577, gnomAD 0.007%). 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: 1463301). 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. 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 RCV002284504 SCV002574334 uncertain significance not provided 2022-09-14 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV003170208 SCV003860546 uncertain significance Cardiovascular phenotype 2022-12-25 criteria provided, single submitter clinical testing The p.L761P variant (also known as c.2282T>C), located in coding exon 15 of the SCN10A gene, results from a T to C substitution at nucleotide position 2282. The leucine at codon 761 is replaced by proline, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV004734370 SCV005350933 uncertain significance SCN10A-related disorder 2024-06-13 no assertion criteria provided clinical testing The SCN10A c.2282T>C variant is predicted to result in the amino acid substitution p.Leu761Pro. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0064% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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