Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000699317 | SCV000828022 | uncertain significance | Brugada syndrome | 2021-08-31 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine with threonine at codon 50 of the SCN10A protein (p.Lys50Thr). The lysine residue is moderately conserved and there is a moderate physicochemical difference between lysine and threonine. This variant is present in population databases (rs757655001, ExAC 0.03%). This variant has not been reported in the literature in individuals affected with SCN10A-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly 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 | RCV002388297 | SCV002702057 | uncertain significance | Cardiovascular phenotype | 2021-08-06 | criteria provided, single submitter | clinical testing | The p.K50T variant (also known as c.149A>C), located in coding exon 1 of the SCN10A gene, results from an A to C substitution at nucleotide position 149. The lysine at codon 50 is replaced by threonine, an amino acid with similar properties. This alteration has been reported in an autism spectrum disorder cohort; however, clinical details were limited (Patowary A et al. Transl Psychiatry, 2019 01;9:4). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |