Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002392564 | SCV002703871 | uncertain significance | Cardiovascular phenotype | 2021-06-08 | criteria provided, single submitter | clinical testing | The p.G511S variant (also known as c.1531G>A), located in coding exon 11 of the SCN10A gene, results from a G to A substitution at nucleotide position 1531. The glycine at codon 511 is replaced by serine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and serine 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. |
Labcorp Genetics |
RCV003095297 | SCV003005624 | uncertain significance | Brugada syndrome | 2022-04-15 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. This variant has not been reported in the literature in individuals affected with SCN10A-related conditions. This variant is present in population databases (rs758503519, gnomAD 0.01%). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 511 of the SCN10A protein (p.Gly511Ser). |