Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000159226 | SCV000209172 | uncertain significance | not provided | 2014-08-18 | criteria provided, single submitter | clinical testing | A M155V variant of unknown significance was identified in the TNNI3 gene. It has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The M155V variant was not observed in approximately 6,100 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. A missense mutation in the same residue (M155I) was identified in two unrelated Portuguese individuals, and was noted to co-segregate with hypertrophic cardiomyopathy (HCM) in the father of one these individuals (Santos et al., 2012). Furthermore, mutations in nearby residues (R145Q, S150C, A157V) have been reportedin association with HCM, supporting the functional importance of this region of the protein.Based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant.The variant is found in DCM-CRDM panel(s). |
| Labcorp Genetics |
RCV003765000 | SCV004679044 | uncertain significance | Hypertrophic cardiomyopathy | 2024-01-27 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 155 of the TNNI3 protein (p.Met155Val). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 181583). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |