Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002004133 | SCV002292400 | uncertain significance | Brugada syndrome | 2021-09-04 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). 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 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. This sequence change replaces aspartic acid with glutamic acid at codon 330 of the SCN10A protein (p.Asp330Glu). The aspartic acid residue is weakly conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. |
| Ambry Genetics | RCV002386894 | SCV002690999 | uncertain significance | Cardiovascular phenotype | 2021-10-11 | criteria provided, single submitter | clinical testing | The p.D330E variant (also known as c.990C>A), located in coding exon 8 of the SCN10A gene, results from a C to A substitution at nucleotide position 990. The aspartic acid at codon 330 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is conserved. 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. |