Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000159254 | SCV000209200 | uncertain significance | not provided | 2013-07-29 | criteria provided, single submitter | clinical testing | The Stop211Leu variant in the TNNI3 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Stop211Leu was not observed in approximately 6000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Stop211Leu changes the normal Stop codon to a Leucine codon, leading to the addition of other amino acids at the C-terminal end of the TNNI3 protein. However, in the absence of mRNA studies, the functional consequence of the extension of the protein is unknown. The variant is found in DCM panel(s). |
Laboratory for Molecular Medicine, |
RCV001195633 | SCV001366032 | uncertain significance | not specified | 2019-06-11 | criteria provided, single submitter | clinical testing | The p.X211LeuextX21 variant in TNNI3 has not been previously reported in individuals with cardiomyopathy but has been identified in 0.002% (2/128712) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). It has also been reported in ClinVar (Variation ID 181596). This stop loss variant changes the normal stop codon to a leucine (Leu), which is predicted to result in a 21 amino acid extension of the protein. The functional impact of this change is unclear. In summary, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2, PM4. |
Invitae | RCV002515086 | SCV003485212 | uncertain significance | Hypertrophic cardiomyopathy | 2023-11-15 | criteria provided, single submitter | clinical testing | This sequence change disrupts the translational stop signal of the TNNI3 mRNA. It is expected to extend the length of the TNNI3 protein by 20 additional amino acid residues. This variant is present in population databases (rs730881084, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with TNNI3-related conditions. ClinVar contains an entry for this variant (Variation ID: 181596). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Revvity Omics, |
RCV000159254 | SCV003827697 | uncertain significance | not provided | 2020-02-24 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001195633 | SCV004222906 | uncertain significance | not specified | 2023-11-20 | criteria provided, single submitter | clinical testing | Variant summary: TNNI3 c.632G>T (p.X211LeuextX20) changes the termination codon and is predicted to lead to an extended protein with additional amino acids added to the normal C-terminus. The variant allele was found at a frequency of 4e-06 in 249570 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.632G>T in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |