Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000493578 | SCV000583097 | uncertain significance | not provided | 2017-05-25 | criteria provided, single submitter | clinical testing | The E260K variant of uncertain significance in the TNNT2 gene has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The E260K variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, this variant lacks observation in a significant number of affected individuals, segregation data, and functional evidence, which would further clarify its pathogenicity. |
Invitae | RCV000646062 | SCV000767819 | uncertain significance | Hypertrophic cardiomyopathy 2; Dilated cardiomyopathy 1D; Cardiomyopathy, familial restrictive, 3 | 2023-08-08 | 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 specifically for the TNNT2 gene suggests that this missense change is likely to be deleterious (PMID: 21310275). ClinVar contains an entry for this variant (Variation ID: 430315). This variant has not been reported in the literature in individuals affected with TNNT2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 260 of the TNNT2 protein (p.Glu260Lys). |
Clinical Center for Gene Diagnosis and Therapy, |
RCV003319201 | SCV003932386 | uncertain significance | Primary dilated cardiomyopathy | 2023-06-01 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV003449389 | SCV004180529 | uncertain significance | Dilated cardiomyopathy 1D | 2023-04-11 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV003449390 | SCV004180530 | uncertain significance | Cardiomyopathy, familial restrictive, 3 | 2023-04-11 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV003449388 | SCV004180532 | uncertain significance | Hypertrophic cardiomyopathy 2 | 2023-04-11 | criteria provided, single submitter | clinical testing |