ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.5783G>A (p.Arg1928His) (rs727504822)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000156161 SCV000205877 uncertain significance not specified 2013-11-08 criteria provided, single submitter clinical testing The Arg1929His variant in SCN5A has not been previously reported in individuals with cardiomyopathy or in large population studies. Computational analyses (bioc hemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. Additional i nformation is needed to fully assess the clinical significance of the Arg1929His variant.
Invitae RCV000531920 SCV000637192 uncertain significance Brugada syndrome 2020-08-20 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 1929 of the SCN5A protein (p.Arg1929His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs727504822, ExAC 0.009%). This variant has not been reported in the literature in individuals with an SCN5A-related disease. ClinVar contains an entry for this variant (Variation ID: 179372). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C2). In summary, this variant has uncertain impact on SCN5A function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 5
Ambry Genetics RCV000621933 SCV000738030 uncertain significance Cardiovascular phenotype 2019-01-06 criteria provided, single submitter clinical testing The p.R1929H variant (also known as c.5786G>A), located in coding exon 27 of the SCN5A gene, results from a G to A substitution at nucleotide position 5786. The arginine at codon 1929 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics,Fulgent Genetics RCV000765731 SCV000897099 uncertain significance Brugada syndrome 1; Long QT syndrome 3; Sick sinus syndrome 1, autosomal recessive; Progressive familial heart block, type 1A; Paroxysmal familial ventricular fibrillation 1; Dilated cardiomyopathy 1E; SUDDEN INFANT DEATH SYNDROME; Atrial fibrillation, familial, 10 2018-10-31 criteria provided, single submitter clinical testing
Color Health, Inc RCV001189970 SCV001357371 uncertain significance Arrhythmia 2019-12-18 criteria provided, single submitter clinical testing

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