Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000183040 | SCV000235449 | uncertain significance | not provided | 2018-11-13 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016; McVean et al., 2012; Exome Variant Server); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Reported as a variant of uncertain significance in ClinVar but additional evidence is not available (ClinVar SCV000545041.2; Landrum et al., 2016); Identified in several asymptomatic relatives of an individual referred for sudden cardiac arrest/arrhythmia genetic testing at GeneDx; Identified in two asymptomatic relatives of unexplained cardiac arrest survivors (Steinberg et al., 2016); This variant is associated with the following publications: (PMID: 30059973, 27635072) |
| Labcorp Genetics |
RCV000183040 | SCV000545041 | uncertain significance | not provided | 2022-07-23 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 201498). 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. 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. This missense change has been observed in individual(s) with SCN5A-related conditions (PMID: 30059973). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1210 of the SCN5A protein (p.Phe1210Ser). |
| Fulgent Genetics, |
RCV002485219 | SCV002785605 | 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 | 2021-07-07 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV004804801 | SCV005428296 | uncertain significance | Cardiac arrhythmia | 2024-08-13 | criteria provided, single submitter | clinical testing | This missense variant replaces phenylalanine with serine at codon 1210 of the SCN5A protein. This variant is found within the highly conserved transmembrane domain DIII (a.a. 1207-1466). Rare non-truncating variants in this region have been shown to be significantly overrepresented in individuals with Brugada syndrome and long QT syndrome (PMID: 32893267). Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in a survivor of unexplained cardiac arrest as well as in two asymptomatic relatives in the family (PMID: 27635072). This variant has not been identified 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. |