Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001841088 | SCV001356816 | uncertain significance | Cardiac arrhythmia | 2023-08-02 | criteria provided, single submitter | clinical testing | This missense variant replaces methionine with arginine at codon 463 of the SCN5A protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with SCN5A-related disorders in the literature. This variant has been identified in 2/248608 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Labcorp Genetics |
RCV001295468 | SCV001484388 | uncertain significance | Brugada syndrome | 2021-08-26 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine with arginine at codon 463 of the SCN5A protein (p.Met463Arg). The methionine residue is highly conserved and there is a moderate physicochemical difference between methionine and arginine. This variant is present in population databases (rs761628195, ExAC 0.002%). This variant has not been reported in the literature in individuals affected with SCN5A-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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. |
| Fulgent Genetics, |
RCV002497659 | SCV002814373 | uncertain significance | Brugada syndrome 1; Long QT syndrome 3; Sick sinus syndrome 1; Progressive familial heart block, type 1A; Ventricular fibrillation, paroxysmal familial, type 1; Dilated cardiomyopathy 1E; SUDDEN INFANT DEATH SYNDROME; Atrial fibrillation, familial, 10 | 2021-07-13 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV001841088 | SCV004838939 | uncertain significance | Cardiac arrhythmia | 2024-01-03 | criteria provided, single submitter | clinical testing | This missense variant replaces methionine with arginine at codon 463 of the SCN5A protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with SCN5A-related disorders in the literature. This variant has been identified in 2/248608 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |