ClinVar Miner

Submissions for variant NM_006514.4(SCN10A):c.2749A>G (p.Ile917Val)

gnomAD frequency: 0.00001  dbSNP: rs995638455
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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 RCV002000249 SCV002263688 uncertain significance Brugada syndrome 2023-07-14 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 not expected to disrupt SCN10A protein function. ClinVar contains an entry for this variant (Variation ID: 1480236). This missense change has been observed in individual(s) with Brugada syndrome (PMID: 31292628). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 917 of the SCN10A protein (p.Ile917Val).
Ambry Genetics RCV002441148 SCV002748975 uncertain significance Cardiovascular phenotype 2024-02-17 criteria provided, single submitter clinical testing The p.I917V variant (also known as c.2749A>G), located in coding exon 16 of the SCN10A gene, results from an A to G substitution at nucleotide position 2749. The isoleucine at codon 917 is replaced by valine, an amino acid with highly similar properties. This alteration has been reported in a Brugada syndrome cohort (Monasky MM et al. Europace, 2019 Oct;21:1550-1558). This amino acid position is well conserved in available vertebrate species; however, valine is the reference amino acid in other vertebrate species. 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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