ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.2294C>T (p.Thr765Ile)

dbSNP: rs2061688177
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001066785 SCV001231805 uncertain significance Brugada syndrome 2021-08-26 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 765 of the SCN5A protein (p.Thr765Ile). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with SCN5A-related conditions. 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 RCV002445344 SCV002734158 uncertain significance Cardiovascular phenotype 2018-06-29 criteria provided, single submitter clinical testing The p.T765I variant (also known as c.2294C>T), located in coding exon 14 of the SCN5A gene, results from a C to T substitution at nucleotide position 2294. The threonine at codon 765 is replaced by isoleucine, an amino acid with similar properties, and is located in the DII-S2 transmembrane spanning region of the protein. This amino acid position is not well conserved in available vertebrate species, and isoleucine 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.
Fulgent Genetics, Fulgent Genetics RCV002505646 SCV002814424 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 2022-02-16 criteria provided, single submitter clinical testing

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