Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002335654 | SCV002644378 | uncertain significance | Cardiovascular phenotype | 2021-04-12 | criteria provided, single submitter | clinical testing | The p.A168G variant (also known as c.503C>G), located in coding exon 4 of the SCN10A gene, results from a C to G substitution at nucleotide position 503. The alanine at codon 168 is replaced by glycine, an amino acid with similar properties. This amino acid position is not well 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. |
| Labcorp Genetics |
RCV003096580 | SCV003002772 | uncertain significance | Brugada syndrome | 2022-06-25 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 168 of the SCN10A protein (p.Ala168Gly). This variant is present in population databases (rs558639346, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with SCN10A-related conditions. 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 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. |