ClinVar Miner

Submissions for variant NM_006514.4(SCN10A):c.3766C>T (p.Arg1256Trp)

gnomAD frequency: 0.00002  dbSNP: rs747044382
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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 RCV000638742 SCV000760288 uncertain significance Brugada syndrome 2024-12-17 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1256 of the SCN10A protein (p.Arg1256Trp). This variant is present in population databases (rs747044382, gnomAD 0.01%). 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: 532125). 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 expected to disrupt SCN10A protein function with a positive 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.
Ambry Genetics RCV002343251 SCV002623389 uncertain significance Cardiovascular phenotype 2023-09-18 criteria provided, single submitter clinical testing The p.R1256W variant (also known as c.3766C>T), located in coding exon 21 of the SCN10A gene, results from a C to T substitution at nucleotide position 3766. The arginine at codon 1256 is replaced by tryptophan, an amino acid with dissimilar properties. This variant was detected in an individual with small fiber neuropathy; however, clinical details were limited (Eijkenboom I et al. J Neurol Neurosurg Psychiatry, 2019 03;90:342-352). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear.
Breakthrough Genomics, Breakthrough Genomics RCV004691992 SCV005189637 uncertain significance not provided criteria provided, single submitter not provided

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