Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003539782 | SCV000816302 | uncertain significance | not provided | 2023-09-27 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 1079 of the SCN5A protein (p.Ser1079Phe). This variant is present in population databases (rs199473188, gnomAD 0.0009%). This missense change has been observed in individual(s) with clinical features of SCN5A-related conditions (PMID: 20541041, 28807990). ClinVar contains an entry for this variant (Variation ID: 67784). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests 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, |
RCV002477199 | SCV002775072 | 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 | 2021-08-13 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV003591669 | SCV004361663 | uncertain significance | Cardiac arrhythmia | 2022-05-11 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with phenylalanine at codon 1079 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 been reported in individuals affected with long QT syndrome (PMID: 26669661, 32893267) and in an individual affected with sudden unexpected death (PMID: 28807990). This variant has been identified in 1/242384 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. |
| Cardiovascular Biomedical Research Unit, |
RCV000058556 | SCV000090076 | not provided | Congenital long QT syndrome | no assertion provided | literature only | This variant has been reported as associated with Long QT syndrome in the following publications (PMID:20541041). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory. |