Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002828995 | SCV003213429 | uncertain significance | Brugada syndrome | 2022-08-24 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 497 of the SCN10A protein (p.Arg497His). This variant is present in population databases (rs766682646, gnomAD 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 output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. |
| Ambry Genetics | RCV003382947 | SCV004097841 | uncertain significance | Cardiovascular phenotype | 2023-09-15 | criteria provided, single submitter | clinical testing | The p.R497H variant (also known as c.1490G>A), located in coding exon 11 of the SCN10A gene, results from a G to A substitution at nucleotide position 1490. The arginine at codon 497 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. |