ClinVar Miner

Submissions for variant NM_006514.3(SCN10A):c.365C>T (p.Thr122Met) (rs142884499)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000521403 SCV000618885 uncertain significance not specified 2017-07-10 criteria provided, single submitter clinical testing The T122M variant has not been published as pathogenic or been reported as benign to our knowledge. The T122M variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, 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. Furthermore, the T122M variant has been observed in 0.069%-0.2% of alleles from individuals of East Asian ancestry in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server).
Invitae RCV000229954 SCV000289556 uncertain significance Brugada syndrome 2018-10-26 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 122 of the SCN10A protein (p.Thr122Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs142884499, ExAC 0.07%) but has not been reported in the literature in individuals with a SCN10A-related disease. 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. Furthermore, the methionine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. In summary, this is a rare missense change that is not predicted to affect protein function or cause disease. However, the evidence is insufficient at this time to prove that conclusively. It has been classified as a Variant of Uncertain Significance.
Stanford Center for Inherited Cardiovascular Disease,Stanford University RCV000786213 SCV000924936 uncertain significance not provided 2016-02-19 no assertion criteria provided provider interpretation

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