Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000036578 | SCV000060233 | likely pathogenic | Hypertrophic cardiomyopathy | 2015-03-11 | criteria provided, single submitter | clinical testing | The p.Lys97Asn variant in TNNT2 has been previously reported in 1 individual wit h HCM (Cardiogenomics) and in 1 unaffected individual with a family history of H CM and sudden cardiac death (Maron 2011). In addition, this variant has been ide ntified by our laboratory in 1 adult with DCM and a family history of HCM (possi ble end-stage HCM) and in 1 adult with HCM and was found to segregate with disea se in at least 4 affected relatives from two families, 3 of whom were tested in a research laboratory (LMM unpublished data). This variant was absent from large population studies. Lysine (Lys) at position 97 is highly conserved in evolutio n and the change to asparagine (Asn) was predicted to be pathogenic using a comp utational tool clinically validated by our laboratory. This tool's pathogenic pr ediction is estimated to be correct 94% of the time (Jordan 2011). In summary, a lthough additional studies are required to fully establish its clinical signific ance, the p.Lys97Asn variant is likely pathogenic. |
Blueprint Genetics | RCV000788201 | SCV000927237 | pathogenic | not provided | 2017-04-22 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000791922 | SCV000931191 | pathogenic | Hypertrophic cardiomyopathy 2; Dilated cardiomyopathy 1D; Cardiomyopathy, familial restrictive, 3 | 2023-10-18 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 97 of the TNNT2 protein (p.Lys97Asn). This variant is present in population databases (rs397516459, gnomAD 0.0009%). This missense change has been observed in individuals with TNNT2-related conditions (PMID: 21185001, 25524337, 27532257; Invitae). ClinVar contains an entry for this variant (Variation ID: 43631). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TNNT2 protein function. Experimental studies have shown that this missense change affects TNNT2 function (PMID: 33025817). For these reasons, this variant has been classified as Pathogenic. |
Genome- |
RCV003450691 | SCV004181475 | likely pathogenic | Dilated cardiomyopathy 1D | 2023-04-11 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV003450692 | SCV004181476 | likely pathogenic | Cardiomyopathy, familial restrictive, 3 | 2023-04-11 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV003450690 | SCV004181477 | likely pathogenic | Hypertrophic cardiomyopathy 2 | 2023-04-11 | criteria provided, single submitter | clinical testing | |
Human Genetics Bochum, |
RCV003886369 | SCV004704565 | likely pathogenic | See cases | 2023-11-13 | criteria provided, single submitter | clinical testing | ACMG criteria used to clasify this variant: PS3_MOD, PS4_MOD, PP3_MOD, PM2_SUP |
Stanford Center for Inherited Cardiovascular Disease, |
RCV000223847 | SCV000280520 | uncertain significance | not specified | 2011-12-19 | no assertion criteria provided | clinical testing | Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease |