ClinVar Miner

Submissions for variant NM_006514.4(SCN10A):c.4312G>A (p.Glu1438Lys)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002331980 SCV002627641 uncertain significance Cardiovascular phenotype 2022-01-31 criteria provided, single submitter clinical testing The p.E1438K variant (also known as c.4312G>A), located in coding exon 25 of the SCN10A gene, results from a G to A substitution at nucleotide position 4312. The glutamic acid at codon 1438 is replaced by lysine, an amino acid with similar properties. 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV005058363 SCV005725169 uncertain significance Brugada syndrome 2024-11-22 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1438 of the SCN10A protein (p.Glu1438Lys). This variant is present in population databases (rs370610736, gnomAD 0.002%). 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: 1739643). 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) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SCN10A protein function. 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.

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