Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Blueprint Genetics | RCV000208287 | SCV000263878 | likely pathogenic | Arrhythmogenic right ventricular cardiomyopathy | 2015-06-08 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000427986 | SCV000534595 | pathogenic | not provided | 2022-06-17 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 26656175, 32372669, 26899768, 31402444, Reza_2022_Cardiogenetics) |
Invitae | RCV000529617 | SCV000639746 | pathogenic | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2023-05-25 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the DSP protein in which other variant(s) (p.Glu2728Glyfs*11) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 222582). This premature translational stop signal has been observed in individual(s) with dilated cardiomyopathy (PMID: 26899768). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg1951*) in the DSP gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 921 amino acid(s) of the DSP protein. |
Color Diagnostics, |
RCV001187850 | SCV001354743 | pathogenic | Cardiomyopathy | 2023-06-22 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 24 of the DSP gene, creating a premature translation stop signal in the last exon. Although functional studies have not been reported, this variant is predicted to escape nonsense-mediated decay and be expressed as a truncated protein with disruption to the plakin repeat domains and downstream C-terminal sequence that have been reported to be essential for interaction with intermediate filaments (PMID: 12101406, 12802069, 21756917). This variant has been reported in 6 unrelated individuals affected with arrhythmogenic cardiomyopathy (PMID: 35474678, 36768812, Delpon 2016, Burns 2019, dissertation, The University of Sydney), in 1 individual affected with familial dilated cardiomyopathy (PMID: 26899768), hypertrophic cardiomyopathy (PMID: 26656175), and acute myocarditis (PMID: 34368507). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic. |
Sangiuolo Lab - |
RCV002515542 | SCV003760914 | pathogenic | Arrhythmogenic cardiomyopathy | 2023-01-10 | no assertion criteria provided | clinical testing |