Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000638727 | SCV000760269 | uncertain significance | Brugada syndrome | 2017-09-19 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine with leucine at codon 1223 of the SCN10A protein (p.Phe1223Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine. 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 disease. 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"). 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 | RCV003162857 | SCV003860529 | uncertain significance | Cardiovascular phenotype | 2022-11-15 | criteria provided, single submitter | clinical testing | The p.F1223L variant (also known as c.3667T>C), located in coding exon 20 of the SCN10A gene, results from a T to C substitution at nucleotide position 3667. The phenylalanine at codon 1223 is replaced by leucine, an amino acid with highly similar 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. |