ClinVar Miner

Submissions for variant NM_000364.4(TNNT2):c.286G>A (p.Asp96Asn) (rs1553282768)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000546244 SCV000646893 uncertain significance Familial hypertrophic cardiomyopathy 2; Left ventricular noncompaction 6; Familial restrictive cardiomyopathy 3 2017-12-18 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 86 of the TNNT2 protein (p.Asp86Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. 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. A computational algorithm designed to assess the pathogenicity of variants in TNNT2 with regard to hypertrophic cardiomyopathy predicted this sequence change to be deleterious. The algorithm has a sensitivity of 94% and a specificity of 89% (PMID: 21310275). A different missense substitution at this codon (p.Asp86Ala) has been determined to be pathogenic (PMID: 12860912, 26914223, 25524337, 27532257). This suggests that the aspartic acid 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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