ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.1613G>A (p.Gly538Asp)

gnomAD frequency: 0.00001  dbSNP: rs779486899
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001842691 SCV001341719 uncertain significance Cardiac arrhythmia 2023-06-21 criteria provided, single submitter clinical testing This missense variant replaces glycine with aspartic acid at codon 538 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 SCN5A-related disorders in the literature. This variant has been identified in 1/248560 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.
Ambry Genetics RCV002402531 SCV002705776 uncertain significance Cardiovascular phenotype 2019-11-25 criteria provided, single submitter clinical testing The p.G538D variant (also known as c.1613G>A), located in coding exon 11 of the SCN5A gene, results from a G to A substitution at nucleotide position 1613. The glycine at codon 538 is replaced by aspartic acid, an amino acid with similar properties, and is located in the DI/DII interdomain linker region. This amino acid position is well conserved in available vertebrate species; however, aspartic acid is the reference amino acid in other 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.
All of Us Research Program, National Institutes of Health RCV001842691 SCV004816445 uncertain significance Cardiac arrhythmia 2023-06-26 criteria provided, single submitter clinical testing This missense variant replaces glycine with aspartic acid at codon 538 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 SCN5A-related disorders in the literature. This variant has been identified in 1/248560 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.

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