Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000479180 | SCV000570880 | likely pathogenic | not provided | 2016-07-11 | criteria provided, single submitter | clinical testing | A novel c.8442dupC variant that is likely pathogenic was identified in the DSP gene. It has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant causes a shift in reading frame starting at codon Serine 2815, changing it to a Glutamine, and creating a premature stop codon at position 37 of the new reading frame, denoted p.Ser2815GlnfsX37. This likely pathogenic variant is expected to result in an abnormal, truncated protein product where the last 57 amino acids of the protein are replaced by 36 incorrect amino acids. This truncation may alter the ability of desmoplakin to bind to desmin. However, no studies have been performed to determine the functional effect of the c.8442dupC variant. In addition, no other downstream frameshift variants in the DSP gene have been reported in HGMD (Stenson et al., 2014). Finally, the c.8442dupC variant 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.Therefore, this variant is likely pathogenic. In order to definitively determine its clinical significance, additional data is required. |
| Invitae | RCV001851213 | SCV002304770 | uncertain significance | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2021-08-24 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ser2815Glnfs*37) in the DSP gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 57 amino acid(s) of the DSP protein. 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. ClinVar contains an entry for this variant (Variation ID: 421616). This variant has not been reported in the literature in individuals affected with DSP-related conditions. This variant is not present in population databases (ExAC no frequency). |