ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.3343C>T (p.Arg1115Trp)

gnomAD frequency: 0.00006  dbSNP: rs199473196
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000058567 SCV000637132 uncertain significance not provided 2023-08-17 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1116 of the SCN5A protein (p.Arg1116Trp). This variant is present in population databases (rs199473196, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with SCN5A-related conditions. ClinVar contains an entry for this variant (Variation ID: 67793). 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.
Ambry Genetics RCV000618999 SCV000737862 uncertain significance Cardiovascular phenotype 2022-07-08 criteria provided, single submitter clinical testing The c.3346C>T (p.R1116W) alteration is located in exon 18 (coding exon 17) of the SCN5A gene. This alteration results from a C to T substitution at nucleotide position 3346, causing the arginine (R) at amino acid position 1116 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Athena Diagnostics RCV000058567 SCV000843714 uncertain significance not provided 2018-08-20 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001842335 SCV001736606 uncertain significance Cardiac arrhythmia 2023-03-07 criteria provided, single submitter clinical testing This missense variant replaces arginine with tryptophan at codon 1116 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 not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been reported in two ostensibly healthy individuals (PMID: 20129283). This variant has also been identified in 6/268350 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 RCV000058567 SCV001773190 uncertain significance not provided 2022-12-09 criteria provided, single submitter clinical testing Reported in at least two individuals from a control cohort (Kapa et al., 2009); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 20129283, 19841300, 22581653, 26746457)
Fulgent Genetics, Fulgent Genetics RCV002490657 SCV002789719 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 2021-08-25 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV001842335 SCV004833610 uncertain significance Cardiac arrhythmia 2023-12-01 criteria provided, single submitter clinical testing This missense variant replaces arginine with tryptophan at codon 1116 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 not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been reported in two ostensibly healthy individuals (PMID: 20129283). This variant has also been identified in 6/268350 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.
Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust RCV000058567 SCV000090087 not provided not provided no assertion provided literature only This variant has been reported in the following publications (PMID:19841300;PMID:20129283).

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