Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001175475 | SCV001339056 | uncertain significance | not specified | 2020-03-02 | criteria provided, single submitter | clinical testing | Variant summary: TNNI3 c.34C>T (p.Pro12Ser) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 3.1e-05 in 223542 control chromosomes, predominantly at a frequency of 0.00043 within the East Asian subpopulation in the gnomAD database. 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.34C>T in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Color Diagnostics, |
RCV001182994 | SCV001348638 | uncertain significance | Cardiomyopathy | 2023-09-22 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with serine at codon 12 of the TNNI3 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 8/254898 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| CHEO Genetics Diagnostic Laboratory, |
RCV001182994 | SCV003838367 | uncertain significance | Cardiomyopathy | 2022-03-16 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV003163387 | SCV003911592 | likely benign | Cardiovascular phenotype | 2023-02-20 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |