Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000253227 | SCV000320623 | uncertain significance | Cardiovascular phenotype | 2022-02-09 | criteria provided, single submitter | clinical testing | The p.Q48P variant (also known as c.143A>C), located in coding exon 4 of the TNNI3 gene, results from an A to C substitution at nucleotide position 143. The glutamine at codon 48 is replaced by proline, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV001051959 | SCV001216144 | uncertain significance | Hypertrophic cardiomyopathy | 2023-07-16 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 48 of the TNNI3 protein (p.Gln48Pro). This variant is present in population databases (rs200720341, gnomAD 0.02%). 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: 264596). 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. |
CHEO Genetics Diagnostic Laboratory, |
RCV001798763 | SCV002042728 | uncertain significance | Cardiomyopathy | 2019-12-27 | criteria provided, single submitter | clinical testing | |
Gene |
RCV002253343 | SCV002525440 | uncertain significance | not provided | 2022-03-07 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function |
Foundation for Research in Genetics and Endocrinology, |
RCV000656735 | SCV000778807 | uncertain significance | Dilated cardiomyopathy 2A | 2018-06-06 | no assertion criteria provided | clinical testing | The observed variant c.143A>C (p.Gln48Pro) is not reported in 1000 Genomes and its minor allele frequency in ExAC databases is 0.0001253. The in silico prediction of the variant is disease causing by MutationTaster2, Tolerated by SIFT and possibly damaging by PolyPhen2. |