ClinVar Miner

Submissions for variant NM_000363.5(TNNI3):c.205C>A (p.Arg69Ser) (rs1555864037)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000544914 SCV000623777 uncertain significance Hypertrophic cardiomyopathy 2017-04-21 criteria provided, single submitter clinical testing This sequence change replaces arginine with serine at codon 69 of the TNNI3 protein (p.Arg69Ser). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and serine. This variant is not present in population databases (ExAC no frequency) and 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 deleterious. The algorithm has a sensitivity of 94% and a specificity of 89% (PMID: 21310275). The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

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