Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000534987 | SCV000637032 | uncertain significance | Brugada syndrome | 2017-06-19 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This sequence change replaces proline with threonine at codon 1791 of the SCN10A protein (p.Pro1791Thr). The proline residue is moderately conserved and there is a small physicochemical difference between proline and threonine. This variant is present in population databases (rs371803816, ExAC 0.001%). This variant has not been reported in the literature in individuals with an SCN10A-related disease. In summary, this variant has uncertain impact on SCN10A function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV002350241 | SCV002646455 | uncertain significance | Cardiovascular phenotype | 2019-12-10 | criteria provided, single submitter | clinical testing | The p.P1791T variant (also known as c.5371C>A), located in coding exon 27 of the SCN10A gene, results from a C to A substitution at nucleotide position 5371. The proline at codon 1791 is replaced by threonine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. 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. |