ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.2923C>T (p.Arg975Trp)

gnomAD frequency: 0.00001  dbSNP: rs41311135
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000058537 SCV000545022 uncertain significance not provided 2023-12-19 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 975 of the SCN5A protein (p.Arg975Trp). This variant is present in population databases (rs41311135, gnomAD 0.006%). This missense change has been observed in individuals with clinical features of SCN5A-related conditions (PMID: 26669661, 32145446; Invitae). ClinVar contains an entry for this variant (Variation ID: 67767). 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.
CeGaT Center for Human Genetics Tuebingen RCV000058537 SCV001153869 uncertain significance not provided 2016-11-01 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001842321 SCV001346806 uncertain significance Cardiac arrhythmia 2023-06-01 criteria provided, single submitter clinical testing This missense variant replaces arginine with tryptophan at codon 975 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 performed for this variant. This variant has been reported in the literature in two related individuals affected with long QT syndrome (PMID: 26669661, 27816319), in an individual referred for long QT syndrome genetic testing (PMID: 20129283), and in two infants affected with sudden death (PMID: 19322600, 32145446). This variant has also been observed in healthy control individuals (PMID: 15851227, 19841300). This variant has been identified in 8/241596 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.
Fulgent Genetics, Fulgent Genetics RCV002477198 SCV002787136 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 2021-12-20 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV001842321 SCV004822745 uncertain significance Cardiac arrhythmia 2024-01-11 criteria provided, single submitter clinical testing This missense variant replaces arginine with tryptophan at codon 975 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 performed for this variant. This variant has been reported in the literature in two related individuals affected with long QT syndrome (PMID: 26669661, 27816319), in an individual referred for long QT syndrome genetic testing (PMID: 20129283), and in two infants affected with sudden death (PMID: 19322600, 32145446). This variant has also been observed in healthy control individuals (PMID: 15851227, 19841300). This variant has been identified in 8/241596 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 RCV004019044 SCV004943829 uncertain significance Cardiovascular phenotype 2022-07-07 criteria provided, single submitter clinical testing The c.2923C>T (p.R975W) alteration is located in exon 17 (coding exon 16) of the SCN5A gene. This alteration results from a C to T substitution at nucleotide position 2923, causing the arginine (R) at amino acid position 975 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust RCV000058537 SCV000090057 not provided not provided no assertion provided literature only This variant has been reported in the following publications (PMID:15851227;PMID:19322600;PMID:19841300;PMID:20129283).

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