Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000530156 | SCV000623776 | uncertain significance | Hypertrophic cardiomyopathy | 2024-10-10 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 62 of the TNNI3 protein (p.Glu62Lys). This variant is not present in population databases (gnomAD no frequency). 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: 454402). An algorithm developed specifically for the TNNI3 gene suggests that this missense change is likely to be deleterious (PMID: 21310275). 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. |
| Stanford Center for Inherited Cardiovascular Disease, |
RCV000786225 | SCV000924963 | uncertain significance | not provided | 2017-12-04 | no assertion criteria provided | provider interpretation | We identified in this variant in a patient with personal and family history of DCM. Testing was performed at Invitae. SCICD Classification: variant of uncertain significance based on absence in the general population and lack of case data. We do not feel it is suitable for assessing risk in healthy relatives ("predictive genetic testing"). Gene-level evidence: TNNI3 encodes the cardiac muscle isoform of troponin I. It has been associated with hypertrophic, dilated, and restrictive cardiomyopathy. Case data (not including our patient): 0 · ClinVar: not present · Cases in the literature: none reported Segregation data: none reported Functional data: none reported In silico data (missense variants only): Per the test report, "An algorithm developed specifically for the TNNI3 gene (PMID: 21310275), suggests that this missense change is likely to be deleterious. The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine." Nearby pathogenic variants at this codon or neighboring codons: None Population data: Absent The variant is not present in the Genome Aggregation Consortium Dataset (gnomAD; http://gnomad.broadinstitute.org/), which currently includes variant calls on >140,000 unrelated individuals of African, Asian, European, Latino, and Ashkenazi descent. Per Varsome.org, the average coverage at that site in genomes is 32x whereas in exomes it is 67x. |