Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000697228 | SCV000825825 | uncertain significance | Brugada syndrome | 2022-08-16 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 533 of the SCN5A protein (p.Arg533Cys). This variant is present in population databases (rs775576991, gnomAD 0.006%). This missense change has been observed in individual(s) with long QT syndrome as compound heterozygous with another variant in SCN5A and/or SCN5A-related conditions (PMID: 27485560, 30847666). ClinVar contains an entry for this variant (Variation ID: 575108). 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. |
| Color Diagnostics, |
RCV001841866 | SCV000908006 | uncertain significance | Cardiac arrhythmia | 2019-07-09 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with cysteine at codon 533 of the SCN5A protein. Computational prediction tools and conservation analyses suggest that this variant may have deleterious impact on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 5/278818 chromosomes in the general population by the Genome Aggregation Database (gnomAD). 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. |
| Ambry Genetics | RCV002397426 | SCV002706855 | uncertain significance | Cardiovascular phenotype | 2021-12-07 | criteria provided, single submitter | clinical testing | The p.R533C variant (also known as c.1597C>T), located in coding exon 11 of the SCN5A gene, results from a C to T substitution at nucleotide position 1597. The arginine at codon 533 is replaced by cysteine, an amino acid with highly dissimilar properties. This variant was detected in an arrhythmia genetic testing cohort; however, clinical details were limited (van Lint FHM et al. Neth Heart J, 2019 Jun;27:304-309). This amino acid position is well 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. |
| Fulgent Genetics, |
RCV002485696 | SCV002784491 | 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 | 2021-08-12 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV001841866 | SCV004831382 | uncertain significance | Cardiac arrhythmia | 2024-09-23 | criteria provided, single submitter | clinical testing |