Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003656844 | SCV001505315 | uncertain significance | not provided | 2023-08-10 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1015850). This variant has not been reported in the literature in individuals affected with SCN5A-related conditions. This variant is present in population databases (rs199473155, gnomAD 0.008%). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 759 of the SCN5A protein (p.Ile759Val). 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 tolerated. 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, |
RCV001841205 | SCV002052657 | uncertain significance | Cardiac arrhythmia | 2023-07-24 | criteria provided, single submitter | clinical testing | This missense variant replaces isoleucine with valine at codon 759 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). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 2/280620 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. |
| Ambry Genetics | RCV002447332 | SCV002732122 | uncertain significance | Cardiovascular phenotype | 2020-08-14 | criteria provided, single submitter | clinical testing | The p.I759V variant (also known as c.2275A>G), located in coding exon 14 of the SCN5A gene, results from an A to G substitution at nucleotide position 2275. The isoleucine at codon 759 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly 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, |
RCV002499609 | SCV002814948 | 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 | 2021-09-13 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV001841205 | SCV004825857 | uncertain significance | Cardiac arrhythmia | 2023-11-30 | criteria provided, single submitter | clinical testing | This missense variant replaces isoleucine with valine at codon 759 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). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 2/280620 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. |