Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000638743 | SCV000760289 | uncertain significance | Brugada syndrome | 2022-08-22 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 826 of the SCN10A protein (p.Asp826Tyr). This variant is present in population databases (rs199535863, gnomAD 0.02%). 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: 532126). 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. 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. |
Ce |
RCV000998046 | SCV001153910 | uncertain significance | not provided | 2019-03-01 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002448983 | SCV002734620 | uncertain significance | Cardiovascular phenotype | 2024-01-13 | criteria provided, single submitter | clinical testing | The p.D826Y variant (also known as c.2476G>T), located in coding exon 15 of the SCN10A gene, results from a G to T substitution at nucleotide position 2476. The aspartic acid at codon 826 is replaced by tyrosine, an amino acid with highly dissimilar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |