Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000181371 | SCV000233672 | pathogenic | not provided | 2019-07-22 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek et al., 2016); Frameshift variant predicted to result in protein truncation in a gene for which loss-of-function is a known mechanism of disease |
Invitae | RCV000806504 | SCV000946508 | pathogenic | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2020-09-15 | criteria provided, single submitter | clinical testing | This sequence change results in a premature translational stop signal in the DSP gene (p.Asn2171Leufs*17). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 701 amino acids of the DSP protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with DSP-related disease. ClinVar contains an entry for this variant (Variation ID: 199927). This variant disrupts the C-terminus of the DSP protein. Other variant(s) that disrupt this region (p.Thr2625Argfs*18, p.Ile2359Serfs*10, p.His2195Tyrfs*26) have been determined to be pathogenic (Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic. |