Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001060807 | SCV001225519 | uncertain significance | Brugada syndrome | 2020-02-21 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with alanine at codon 51 of the SCN10A protein (p.Pro51Ala). The proline residue is highly conserved and there is a small physicochemical difference between proline and alanine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 | RCV002393298 | SCV002708608 | uncertain significance | Cardiovascular phenotype | 2021-07-30 | criteria provided, single submitter | clinical testing | The p.P51A variant (also known as c.151C>G), located in coding exon 1 of the SCN10A gene, results from a C to G substitution at nucleotide position 151. The proline at codon 51 is replaced by alanine, 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. |