ClinVar Miner

Submissions for variant NM_000364.4(TNNT2):c.877C>A (p.Arg293Ser)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000699850 SCV000828579 uncertain significance Familial hypertrophic cardiomyopathy 2; Left ventricular noncompaction 6; Familial restrictive cardiomyopathy 3 2018-02-23 criteria provided, single submitter clinical testing This sequence change replaces arginine with serine at codon 286 of the TNNT2 protein (p.Arg286Ser). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TNNT2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Different missense substitutions at this codon (p.Arg286His and p.Arg286Cys) have been determined to be pathogenic (PMID: 12860912, 26507537, 12707239, 23785128). This suggests that the arginine residue is critical for TNNT2 protein function and that other missense substitutions at this position may also be pathogenic. 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.

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