ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.616A>T (p.Thr206Ser)

gnomAD frequency: 0.00001  dbSNP: rs1484635042
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003655207 SCV000836402 uncertain significance not provided 2022-04-20 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 206 of the SCN5A protein (p.Thr206Ser). This variant has not been reported in the literature in individuals affected with SCN5A-related conditions. ClinVar contains an entry for this variant (Variation ID: 583074). 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 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.
Ambry Genetics RCV002352223 SCV002654971 uncertain significance Cardiovascular phenotype 2021-04-24 criteria provided, single submitter clinical testing The p.T206S variant (also known as c.616A>T), located in coding exon 5 of the SCN5A gene, results from an A to T substitution at nucleotide position 616. The threonine at codon 206 is replaced by serine, an amino acid with similar properties, and is located in the transmembrane DI-S3 region of the protein. 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.
Fulgent Genetics, Fulgent Genetics RCV002485778 SCV002781756 uncertain significance Brugada syndrome 1; Long QT syndrome 3; Sick sinus syndrome 1; Progressive familial heart block, type 1A; Ventricular fibrillation, paroxysmal familial, type 1; Dilated cardiomyopathy 1E; SUDDEN INFANT DEATH SYNDROME; Atrial fibrillation, familial, 10 2021-07-19 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003999785 SCV004819672 uncertain significance Cardiac arrhythmia 2023-03-09 criteria provided, single submitter clinical testing This missense variant replaces threonine with serine at codon 206 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.

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