ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.1820G>T (p.Gly607Val)

gnomAD frequency: 0.00001  dbSNP: rs757119370
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182985 SCV000235385 uncertain significance not provided 2023-08-03 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27535533, 26582918)
Ambry Genetics RCV000252061 SCV000318808 uncertain significance Cardiovascular phenotype 2021-09-11 criteria provided, single submitter clinical testing The p.G607V variant (also known as c.1820G>T), located in coding exon 11 of the SCN5A gene, results from a G to T substitution at nucleotide position 1820. The glycine at codon 607 is replaced by valine, an amino acid with dissimilar properties. This alteration has been reported in an individual with a clinical diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC), who was additionally found to have a gross deletion in PKP2 and in a cardiac genetic testing cohort with limited clinical details and additional cardiac variants detected in some cases (Pilichou K et al. Circ Arrhythm Electrophysiol, 2017 Oct;10:[ePub ahead of print]; van Lint FHM et al. Neth Heart J, 2019 Jun;27:304-309). This amino acid position is 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.
Invitae RCV000182985 SCV000637088 uncertain significance not provided 2023-12-31 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 607 of the SCN5A protein (p.Gly607Val). This variant is present in population databases (rs757119370, gnomAD 0.01%). 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: 201461). 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 tolerated. 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.
Color Diagnostics, LLC DBA Color Health RCV001842903 SCV001359811 uncertain significance Cardiac arrhythmia 2022-12-09 criteria provided, single submitter clinical testing This missense variant replaces glycine with valine at codon 607 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 cardiovascular disorders in the literature. This variant has been identified in 13/218670 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.
Laboratory of Medical Genetics, National & Kapodistrian University of Athens RCV001729437 SCV001976858 uncertain significance Brugada syndrome 1 2021-10-05 criteria provided, single submitter clinical testing PM2, PP2, PP3
Fulgent Genetics, Fulgent Genetics RCV002478621 SCV002776830 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 2021-10-13 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV001842903 SCV004823217 uncertain significance Cardiac arrhythmia 2023-12-13 criteria provided, single submitter clinical testing This missense variant replaces glycine with valine at codon 607 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 cardiovascular disorders in the literature. This variant has been identified in 13/218670 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 RCV000182985 SCV001924195 uncertain significance not provided no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000182985 SCV001929937 uncertain significance not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000182985 SCV001979932 uncertain significance not provided no assertion criteria provided clinical testing

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