ClinVar Miner

Submissions for variant NM_006514.4(SCN10A):c.5186C>T (p.Thr1729Met)

gnomAD frequency: 0.00001  dbSNP: rs751384151
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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 RCV001350127 SCV001544505 uncertain significance Brugada syndrome 2020-10-27 criteria provided, single submitter clinical testing 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SCN10A protein function. This variant has not been reported in the literature in individuals with SCN10A-related conditions. This variant is present in population databases (rs751384151, ExAC 0.003%). This sequence change replaces threonine with methionine at codon 1729 of the SCN10A protein (p.Thr1729Met). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and methionine.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV003238354 SCV002009552 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV002341732 SCV002643739 uncertain significance Cardiovascular phenotype 2021-08-07 criteria provided, single submitter clinical testing The p.T1729M variant (also known as c.5186C>T), located in coding exon 27 of the SCN10A gene, results from a C to T substitution at nucleotide position 5186. The threonine at codon 1729 is replaced by methionine, 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.

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