ClinVar Miner

Submissions for variant NM_000363.5(TNNI3):c.374T>C (p.Ile125Thr) (rs878853956)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000227202 SCV000284658 uncertain significance Hypertrophic cardiomyopathy 2015-11-24 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 125 of the TNNI3 protein (p.Ile125Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature. A computational algorithm designed to assess the pathogenicity of missense variants in TNNI3 with regard to hypertrophic cardiomyopathy predicted this sequence change to be pathogenic. The algorithm has a sensitivity of 94% and a specificity of 89% (PMID: 21310275). This missense change is located within exon 8 of the TNNI3 protein and a high percentage of previously reported TNNI3 missense mutations have been found within either exon 7 or exon 8 (PMID: 15607392). These observations suggest that a novel missense substitution within this exon may affect protein function, but experiments have not been done to test this possibility. In summary, this is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.