ClinVar

Description

The likely pathogenic E165X variant in the TNNI3 gene has not been reported as a pathogenic variant or as a benign variant to our knowledge. This variant was not observed in approximately 6,200 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. E165X is predicted to cause loss of normal protein function by protein truncation (loss of the last 46 amino acids). However, no nonsense variants in the TNNI3 gene have been reported in HGMD (Stenson et al., 2014). Most of the pathogenic variants in TNNI3 reported in HGMD are missense substitutions that affect the calcium sensitivity of contraction. While haploinsufficiency is not a well-established mechanism of disease for the TNNI3 gene, other truncation variants have been reported in HGMD (Stenson et al., 2014). Therefore, this variant is likely pathogenic. In order to definitively determine its clinical significance, additional data is required.