Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000181304 | SCV000233595 | pathogenic | not provided | 2014-04-04 | criteria provided, single submitter | clinical testing | p.Glu882Stop (GAG>TAG): c.2644 G>T in exon 19 of the DSP gene (NM_004415.2). The E882X mutation in the DSP gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. E882X is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. The E882X mutation was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Furthermore, other nonsense mutations in the DSP gene have been reported in association with ARVC. In summary, E882X in the DSP gene is interpreted as a disease-causing mutation. The variant is found in CARDIOMYOPATHY panel(s). |
| Labcorp Genetics |
RCV001852269 | SCV002237676 | pathogenic | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2021-06-22 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with DSP-related conditions. ClinVar contains an entry for this variant (Variation ID: 199873). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Glu882*) 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). |