Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV000774336 | SCV000908038 | uncertain significance | Cardiomyopathy | 2023-02-15 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamine with arginine at codon 130 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 been reported in 3 individuals from one family affected with hypertrophic cardiomyopathy (PMID: 27532257, 32731933). It has also been reported in an individual affected with increased left ventricular wall thickness (PMID: 16754800). This variant has been identified in 1/247986 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. |
Invitae | RCV003586216 | SCV004298451 | uncertain significance | Hypertrophic cardiomyopathy | 2023-03-06 | criteria provided, single submitter | clinical testing | 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. 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 629626). This missense change has been observed in individual(s) with TNNI3-related conditions (PMID: 16754800, 27532257). 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 sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 130 of the TNNI3 protein (p.Gln130Arg). |