Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001054084 | SCV001218379 | uncertain significance | Brugada syndrome | 2022-03-18 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 106 of the SCN5A protein (p.Ser106Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of SCN5A-related conditions (PMID: 29016939, 33213388). ClinVar contains an entry for this variant (Variation ID: 850004). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C55"). Experimental studies have shown that this missense change affects SCN5A function (PMID: 33213388). 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, |
RCV001842601 | SCV001342394 | uncertain significance | Cardiac arrhythmia | 2023-03-24 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with glycine at codon 106 of the SCN5A protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). A functional study has shown that this variant causes an increase in sodium channel current density and affects voltage-dependent activation and inactivation in transfected HEK293 cells (PMID: 33213388). This variant has been reported in two individuals affected with sudden unexplained death or survived cardiac arrest, who showed no ECG abnormalities (PMID: 29016939, 33213388). 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. |
Fulgent Genetics, |
RCV002481984 | SCV002784162 | 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 | 2021-08-26 | criteria provided, single submitter | clinical testing |