ClinVar Miner

Submissions for variant NM_000363.5(TNNI3):c.561G>T (p.Glu187Asp) (rs773184959)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000539276 SCV000623791 uncertain significance Hypertrophic cardiomyopathy 2019-06-19 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with aspartic acid at codon 187 of the TNNI3 protein (p.Glu187Asp). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. This variant is present in population databases (rs773184959, ExAC 0.006%) but has not been reported in the literature in individuals with a TNNI3-related disease. A computational algorithm designed to assess the pathogenicity of variants in TNNI3 with regard to hypertrophic cardiomyopathy predicted this sequence change to be tolerated. The algorithm has a sensitivity of 94% and a specificity of 89% (PMID: 21310275). In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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