Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000780213 | SCV000917296 | likely pathogenic | Cardiomyopathy | 2018-01-25 | criteria provided, single submitter | clinical testing | Variant summary: The DSP c.1825C>T (p.Gln609X) variant results in a premature termination codon, predicted to cause a truncated or absent DSP protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as likely pathogenic/pathogenic by our laboratory (e.g. c.2821C>T (p.Arg941X), c.3337C>T (p.Arg1113X), and c.5126_5127delTC (p.Leu1709fsX24)). This variant is absent frome 246034 control chromosomes (gnomAD). The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories, nor was evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as likely pathogenic. |
| Invitae | RCV001381891 | SCV001580465 | pathogenic | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2023-05-02 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with DSP-related conditions. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 632788). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln609*) in the DSP gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DSP are known to be pathogenic (PMID: 20716751, 24503780, 25227139). |