ClinVar Miner

Submissions for variant NM_006514.4(SCN10A):c.5613G>A (p.Met1871Ile)

gnomAD frequency: 0.00001  dbSNP: rs370483003
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001053077 SCV001217319 uncertain significance Brugada syndrome 2021-09-01 criteria provided, single submitter clinical testing This sequence change replaces methionine with isoleucine at codon 1871 of the SCN10A protein (p.Met1871Ile). The methionine residue is weakly conserved and there is a small physicochemical difference between methionine and isoleucine. This variant is present in population databases (rs370483003, ExAC 0.006%). 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 RCV003307866 SCV004000485 uncertain significance Cardiovascular phenotype 2023-03-16 criteria provided, single submitter clinical testing The p.M1871I variant (also known as c.5613G>A), located in coding exon 27 of the SCN10A gene, results from a G to A substitution at nucleotide position 5613. The methionine at codon 1871 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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