ClinVar Miner

Submissions for variant NM_000335.4(SCN5A):c.3715G>C (p.Glu1239Gln) (rs199473211)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058593 SCV000090113 not provided Brugada syndrome no assertion provided literature only This variant has been reported as associated with Brugada syndrome in the following publications (PMID:11901046). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital RCV000678843 SCV000805032 likely pathogenic not specified 2016-04-18 no assertion criteria provided clinical testing
Color RCV000772089 SCV000905122 uncertain significance Arrhythmia 2018-10-11 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This missense variant is located in the transmembrane domain DIII of the SCN5A protein. Computational prediction tools and conservation analyses suggest that this variant may have deleterious impact on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant. This variant has been reported in an individual affected with Brugada syndrome (PMID: 11901046). This variant has also been identified in 9/246260 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.
Invitae RCV000058593 SCV000545034 uncertain significance Brugada syndrome 2018-09-26 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with glutamine at codon 1240 of the SCN5A protein (p.Glu1240Gln). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and glutamine. This variant is present in population databases (rs199473211, ExAC 0.007%). This variant has been reported in an individual affected with Brugada syndrome (PMID: 11901046). ClinVar contains an entry for this variant (Variation ID: 67818). 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, but these predictions have not been confirmed by published functional studies. 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.

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