ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.6024C>G (p.Asp2008Glu)

gnomAD frequency: 0.00001  dbSNP: rs757114635
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV003541109 SCV001205890 uncertain significance not provided 2024-01-29 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 2009 of the SCN5A protein (p.Asp2009Glu). This variant is present in population databases (rs757114635, gnomAD 0.006%). This missense change has been observed in individual(s) with suspected long QT syndrome (PMID: 31737537). ClinVar contains an entry for this variant (Variation ID: 840267). 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 RCV001842591 SCV001344958 uncertain significance Cardiac arrhythmia 2023-06-08 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with glutamic acid at codon 2009 of the SCN5A protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with long QT syndrome (PMID: 31737537). This variant has been identified in 1/192944 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001251366 SCV001426939 uncertain significance not specified 2020-07-20 criteria provided, single submitter clinical testing Variant summary: SCN5A c.6027C>G (p.Asp2009Glu) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 5.2e-06 in 192944 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.6027C>G in individuals affected with Arrhythmia and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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