Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000795258 | SCV000934707 | uncertain significance | Brugada syndrome | 2021-08-28 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with methionine at codon 873 of the SCN10A protein (p.Val873Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs764470746, ExAC 0.002%). 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: "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. |
Gene |
RCV001759500 | SCV001985266 | uncertain significance | not provided | 2021-05-14 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function |
Mayo Clinic Laboratories, |
RCV001759500 | SCV004226083 | uncertain significance | not provided | 2022-04-18 | criteria provided, single submitter | clinical testing | BS2, PP3 |
Ambry Genetics | RCV004986603 | SCV005499954 | uncertain significance | Cardiovascular phenotype | 2024-08-14 | criteria provided, single submitter | clinical testing | The c.2617G>A (p.V873M) alteration is located in exon 15 (coding exon 15) of the SCN10A gene. This alteration results from a G to A substitution at nucleotide position 2617, causing the valine (V) at amino acid position 873 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |