ClinVar Miner

Submissions for variant NM_006514.4(SCN10A):c.3439C>T (p.Arg1147Cys)

gnomAD frequency: 0.00006  dbSNP: rs373470651
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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 RCV002040305 SCV002299295 uncertain significance Brugada syndrome 2021-09-01 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 1147 of the SCN10A protein (p.Arg1147Cys). The arginine residue is weakly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs373470651, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with SCN10A-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 RCV002458983 SCV002617009 uncertain significance Cardiovascular phenotype 2024-11-09 criteria provided, single submitter clinical testing The c.3439C>T (p.R1147C) alteration is located in exon 19 (coding exon 19) of the SCN10A gene. This alteration results from a C to T substitution at nucleotide position 3439, causing the arginine (R) at amino acid position 1147 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx RCV003318712 SCV004022771 uncertain significance not provided 2023-01-30 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004699643 SCV005203868 uncertain significance not specified 2024-07-02 criteria provided, single submitter clinical testing Variant summary: SCN10A c.3439C>T (p.Arg1147Cys) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 251450 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.3439C>T in individuals affected with SCN10A-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1507997). Based on the evidence outlined above, the variant was classified as uncertain significance.

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