Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001294527 | SCV001483407 | uncertain significance | Brugada syndrome | 2023-12-07 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 203 of the SCN10A protein (p.Gly203Ser). This variant is present in population databases (rs774347834, gnomAD 0.004%). 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: 998639). 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 with a negative predictive value of 80%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus 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 | RCV004035609 | SCV003863404 | uncertain significance | Cardiovascular phenotype | 2023-01-23 | criteria provided, single submitter | clinical testing | Does not currently meet published gene-disease clinical validity criteria for this gene (Smith, 2017) Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |