ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.344G>A (p.Ser115Asn)

dbSNP: rs1203397027
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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 RCV001842759 SCV001343698 uncertain significance Cardiac arrhythmia 2023-06-08 criteria provided, single submitter clinical testing This missense variant replaces serine with asparagine at codon 115 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 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 RCV003541281 SCV001565832 uncertain significance not provided 2022-03-08 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C45"). ClinVar contains an entry for this variant (Variation ID: 920384). This variant has not been reported in the literature in individuals affected with SCN5A-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 115 of the SCN5A protein (p.Ser115Asn).
Ambry Genetics RCV002451366 SCV002617047 uncertain significance Cardiovascular phenotype 2019-05-01 criteria provided, single submitter clinical testing The p.S115N variant (also known as c.344G>A), located in coding exon 2 of the SCN5A gene, results from a G to A substitution at nucleotide position 344. The serine at codon 115 is replaced by asparagine, an amino acid with highly similar properties, and is located in the N-terminal region of the protein. Another variant affecting this codon (p.S115G, c.343A>G) has been detected in a long QT syndrome genetic testing cohort; however, clinical details were not provided (Kapplinger JD et al. Heart Rhythm, 2009 Sep;6:1297-303). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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