Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000181344 | SCV000233641 | pathogenic | not provided | 2020-09-25 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); Nonsense variant predicted to result in protein truncation, where the last 588 amino acid residues are lost, in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 32878047, 32372669, 20400443, 25516398, 30847666) |
Invitae | RCV003765110 | SCV004569740 | pathogenic | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2023-12-06 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg2284*) in the DSP gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 588 amino acid(s) of the DSP protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of DSP-related conditions (PMID: 20400443, 25516398). ClinVar contains an entry for this variant (Variation ID: 199905). This variant disrupts a region of the DSP protein in which other variant(s) (p.Gln2730Serfs*16) have been determined to be pathogenic (PMID: 27532257, 28527814; 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. For these reasons, this variant has been classified as Pathogenic. |