Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003541451 | SCV002183753 | uncertain significance | not provided | 2025-01-12 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1084 of the SCN5A protein (p.Gly1084Ser). This variant is present in population databases (rs199473190, gnomAD 0.01%). This missense change has been observed in individual(s) with long QT syndrome and/or sudden infant death syndrome (PMID: 18596570, 32161207, 34930020). ClinVar contains an entry for this variant (Variation ID: 67786). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on SCN5A function (PMID: 18596570, 34930020). 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, |
RCV002498343 | SCV002781030 | 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 | 2021-08-20 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV003996534 | SCV004830281 | uncertain significance | Brugada syndrome | 2023-06-15 | criteria provided, single submitter | clinical testing | This variant has been reported in individuals with Long QT Syndrome/Brugada syndrome but the phenotype is not well described (PMID: 34930020, 32161207, 18596570, 25856671). This variant is present in 2/244388 total alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/). |
| Cardiovascular Biomedical Research Unit, |
RCV000058558 | SCV000090078 | not provided | SUDDEN INFANT DEATH SYNDROME | no assertion provided | literature only | This variant has been reported as associated with Sudden infant death syndrome in the following publications (PMID:18596570). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory. |