ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.3080G>A (p.Arg1027Gln)

gnomAD frequency: 0.00004  dbSNP: rs763891399
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute RCV000624440 SCV000740417 uncertain significance not specified 2016-06-22 criteria provided, single submitter clinical testing
Invitae RCV001569679 SCV000818929 uncertain significance not provided 2023-11-27 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1027 of the SCN5A protein (p.Arg1027Gln). This variant is present in population databases (rs763891399, gnomAD 0.009%). This missense change has been observed in individual(s) with SCN5A-related conditions (PMID: 17210841, 25904541). ClinVar contains an entry for this variant (Variation ID: 520458). 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 disruptive. 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.
Fulgent Genetics, Fulgent Genetics RCV000765737 SCV000897105 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 2018-10-31 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001841807 SCV001340537 uncertain significance Cardiac arrhythmia 2024-01-17 criteria provided, single submitter clinical testing This missense variant replaces arginine with glutamine at codon 1027 of the SCN5A protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with Brugada syndrome or long QT syndrome (PMID: 1309946, 25904541). This variant has been identified in 14/276396 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 RCV001569679 SCV001793806 likely benign not provided 2015-03-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV002319539 SCV002606826 uncertain significance Cardiovascular phenotype 2022-01-28 criteria provided, single submitter clinical testing The p.R1027Q variant (also known as c.3080G>A), located in coding exon 16 of the SCN5A gene, results from a G to A substitution at nucleotide position 3080. The arginine at codon 1027 is replaced by glutamine, an amino acid with highly similar properties. This variant has been reported in an individual with restricted cardiomyopathy and arrhythmias, who also had a co-occurring variant in TNNT2 (Seidelmann SB et al. Circ Cardiovasc Genet, 2017 Feb;10:[Epub ahead of print]). This variant was also detected in one individual from a long QT cohort; however, functional studies were reportedly normal, and clinical details were limited (Kapplinger JD et al. Circ Cardiovasc Genet, 2015 Aug;8:582-95). This amino acid position is not well 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.
All of Us Research Program, National Institutes of Health RCV001841807 SCV004815258 uncertain significance Cardiac arrhythmia 2023-12-07 criteria provided, single submitter clinical testing This missense variant replaces arginine with glutamine at codon 1027 of the SCN5A protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with Brugada syndrome or long QT syndrome (PMID: 1309946, 25904541). This variant has been identified in 14/276396 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.
Clinical Genetics, Academic Medical Center RCV001569679 SCV001917098 uncertain significance not provided no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV001569679 SCV001929194 uncertain significance not provided no assertion criteria provided clinical testing

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