Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001899116 | SCV002170084 | uncertain significance | Brugada syndrome | 2021-06-07 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with glutamic acid at codon 1235 of the SCN10A protein (p.Ala1235Glu). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals 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. |
| Ambry Genetics | RCV002344006 | SCV002622014 | uncertain significance | Cardiovascular phenotype | 2024-10-14 | criteria provided, single submitter | clinical testing | The p.A1235E variant (also known as c.3704C>A), located in coding exon 21 of the SCN10A gene, results from a C to A substitution at nucleotide position 3704. The alanine at codon 1235 is replaced by glutamic acid, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |