ClinVar Miner

Submissions for variant NM_000363.5(TNNI3):c.570C>G (p.Asp190Glu) (rs1131691856)

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
GeneDx RCV000494218 SCV000583009 uncertain significance not provided 2017-05-24 criteria provided, single submitter clinical testing Although the D190E variant of uncertain significance in the TNNI3 gene has not been published as pathogenic or been reported as benign to our knowledge, variants affecting the same residue (D190G, D190Y) have been reported in association with RCM and HCM (Mogensen et al., 2003; Walsh et al., 2017). However, while the D190G and D190Y variants are non-conservative amino acid substitution, which are likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties, the D190E variant is conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Nevertheless, the D190E variant occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Additionally, missense variants in nearby residues (R186Q, R192H, N194S) have been reported in the Human Gene Mutation Database in association with HCM and RCM (Stenson et al., 2014), supporting the functional importance of this residue and this region of the protein. Furthermore, the D190E variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Despite this, the D190E variant lacks observation in a significant number of affected individuals, segregation data, and functional evidence, which would further clarify its pathogenicity.

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.