ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.1324A>G (p.Lys442Glu)

gnomAD frequency: 0.00001  dbSNP: rs1293526829
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001842656 SCV001340704 uncertain significance Cardiac arrhythmia 2023-10-12 criteria provided, single submitter clinical testing This missense variant replaces lysine with glutamic acid at codon 442 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 been reported in an individual affected with long QT syndrome (PMID: 32161207). 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.
Ambry Genetics RCV002379680 SCV002690466 uncertain significance Cardiovascular phenotype 2019-08-15 criteria provided, single submitter clinical testing The p.K442E variant (also known as c.1324A>G), located in coding exon 9 of the SCN5A gene, results from an A to G substitution at nucleotide position 1324. The lysine at codon 442 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is well conserved in available 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV003769884 SCV002950943 uncertain significance not provided 2024-11-18 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 442 of the SCN5A protein (p.Lys442Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with long QT Syndrome (PMID: 32161207). ClinVar contains an entry for this variant (Variation ID: 918832). 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.
All of Us Research Program, National Institutes of Health RCV001842656 SCV004841829 uncertain significance Cardiac arrhythmia 2023-11-02 criteria provided, single submitter clinical testing This missense variant replaces lysine with glutamic acid at codon 442 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 been reported in an individual affected with long QT syndrome (PMID: 32161207). 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.
GeneDx RCV003769884 SCV005079450 uncertain significance not provided 2024-07-12 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 32161207)

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