ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.5464G>A (p.Glu1822Lys)

gnomAD frequency: 0.00003  dbSNP: rs760837591
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001550377 SCV000291820 uncertain significance not provided 2022-11-29 criteria provided, single submitter clinical testing 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C55"). ClinVar contains an entry for this variant (Variation ID: 242204). This variant has not been reported in the literature in individuals affected with SCN5A-related conditions. This variant is present in population databases (rs760837591, gnomAD 0.01%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1823 of the SCN5A protein (p.Glu1823Lys).
Color Diagnostics, LLC DBA Color Health RCV001843006 SCV001357073 uncertain significance Cardiac arrhythmia 2023-06-08 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with lysine at codon 1823 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 not been reported in individuals affected with SCN5A-related disorders in the literature. This variant has been identified in 3/281038 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.
GeneDx RCV001550377 SCV001770693 uncertain significance not provided 2021-09-21 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function
Ambry Genetics RCV002347919 SCV002653860 uncertain significance Cardiovascular phenotype 2022-08-18 criteria provided, single submitter clinical testing The p.E1823K variant (also known as c.5467G>A), located in coding exon 27 of the SCN5A gene, results from a G to A substitution at nucleotide position 5467. The glutamic acid at codon 1823 is replaced by lysine, an amino acid with similar properties. This amino acid position is well 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, Fulgent Genetics RCV002494672 SCV002794104 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 2021-10-14 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV001843006 SCV004829103 uncertain significance Cardiac arrhythmia 2023-09-18 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with lysine at codon 1823 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 not been reported in individuals affected with SCN5A-related disorders in the literature. This variant has been identified in 3/281038 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.

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