ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.5403C>G (p.Asp1801Glu)

dbSNP: rs1367727373
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001841905 SCV000907321 uncertain significance Cardiac arrhythmia 2023-10-22 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with glutamic acid at codon 1802 of the SCN5A protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). This variant is found within a highly conserved C-terminus region (a.a. 1772-2016). Rare non-truncating variants in this region have been shown to be significantly overrepresented in individuals with Brugada syndrome and long QT syndrome (PMID: 32893267). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with SCN5A-related disorders in the literature. 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 RCV003541558 SCV002275520 uncertain significance not provided 2022-05-25 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 1802 of the SCN5A protein (p.Asp1802Glu). This variant is not present in population databases (gnomAD no frequency). 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: 628960). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest 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 RCV002477760 SCV002775571 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 2021-09-15 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV001841905 SCV004826981 uncertain significance Cardiac arrhythmia 2023-11-02 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with glutamic acid at codon 1802 of the SCN5A protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). This variant is found within a highly conserved C-terminus region (a.a. 1772-2016). Rare non-truncating variants in this region have been shown to be significantly overrepresented in individuals with Brugada syndrome and long QT syndrome (PMID: 32893267). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with SCN5A-related disorders in the literature. 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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