Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000214350 | SCV000271741 | uncertain significance | not specified | 2015-07-02 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Pathogenic. The p.Gln2204X variant in DSP has not been previously reported in individuals with cardiomyopat hy and was absent from large population studies. This nonsense variant leads to a premature termination codon within the last exon. Nonsense variants are well r eported patients with ARVC (http://arvcdatabase.info/) and this type of variant is generally expected to lead to nonsense medicated mRNA decay (NMD), resulting in loss of function. However, this is less likely in the last exon and therefore the effect of this variant on the protein is not clear. Some evidence for a rol e in ARVC comes from reports of homozygous truncating variants in the last exon in individuals with Carvajal syndrome and/or acantholytic epidermolysis bullosa (Cheong 2005, Jonkman 2005, Rasmussen 2013), though it is less clear if heterozy gous carriers exhibit any features. In summary, while there is some suspicion f or a pathogenic role, the clinical significance of the p.Gln2204X variant is unc ertain. |