ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.3214_3215inv (p.Glu1072Ser)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000598842 SCV000710285 uncertain significance not provided 2020-07-17 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek et al., 2016); Reported in ClinVar as variant of uncertain significance but additional evidence is not available (ClinVar Variant ID #503982; Landrum et al., 2016); Deletion of two base pairs and insertion of two different base pairs, which leads to the replacement of a glutamic acid (E) residue with a serine (S) residue at codon position 1072, denoted as E1072S; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 33221895)
Color Diagnostics, LLC DBA Color Health RCV001841489 SCV001343146 uncertain significance Cardiac arrhythmia 2023-06-26 criteria provided, single submitter clinical testing This missense variant (also known as c.3214_3215delinsTC in published literature due to the use of alternate nomenclature) replaces glutamic acid with serine at codon 1072 of the SCN5A protein. To our knowledge, functional studies have not been performed for this variant. This variant has been reported in individual(s) affected with Brugada syndrome (PMID: 33221895, 36516610). This variant has not been identified 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.
Invitae RCV000598842 SCV001401399 uncertain significance not provided 2024-01-24 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with serine, which is neutral and polar, at codon 1072 of the SCN5A protein (p.Glu1072Ser). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This missense change has been observed in individual(s) with Brugada syndrome (PMID: 33221895). ClinVar contains an entry for this variant (Variation ID: 503982). 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.
Ambry Genetics RCV002325138 SCV002610751 uncertain significance Cardiovascular phenotype 2022-11-03 criteria provided, single submitter clinical testing The c.3214_3215delGAinsTC variant, located in coding exon 16 of the SCN5A gene, results from an in-frame deletion of GA and insertion of TC at nucleotide positions 3214 to 3215. This results in the substitution of the glutamic acid residue for a serine residue at codon 1072, an amino acid with similar properties. This alteration has been reported in a Brugada syndrome cohort; however, clinical details were limited (Ciconte G et al. Eur Heart J, 2021 03;42:1082-1090). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be neutral by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002491229 SCV002778852 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 2021-11-04 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV001841489 SCV004833372 uncertain significance Cardiac arrhythmia 2023-10-02 criteria provided, single submitter clinical testing This missense variant (also known as c.3214_3215delinsTC in published literature due to the use of alternate nomenclature) replaces glutamic acid with serine at codon 1072 of the SCN5A protein. To our knowledge, functional studies have not been performed for this variant. This variant has been reported in individual(s) affected with Brugada syndrome (PMID: 33221895, 36516610). This variant has not been identified 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.

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