ClinVar Miner

Submissions for variant NM_006514.3(SCN10A):c.1430C>T (p.Pro477Leu) (rs142235256)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000231917 SCV000289548 uncertain significance Brugada syndrome 2018-05-09 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 477 of the SCN10A protein (p.Pro477Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs142235256, ExAC 0.07%) but has not been reported in the literature in individuals with a SCN10A-related disease. ClinVar contains an entry for this variant (Variation ID: 240663). The leucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. In addition, 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 tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function, and is found in the population at an appreciable frequency. This variant is not anticipated to cause disease; however, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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