Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000826162 | SCV000967699 | likely pathogenic | Primary dilated cardiomyopathy; Arrhythmogenic right ventricular cardiomyopathy | 2018-05-24 | criteria provided, single submitter | clinical testing | The p.Ala1145fs variant in DSP has not been previously reported in individuals w ith cardiomyopathy and was absent from large population studies. This variant is located within exon 23 of DSP which undergoes alternative splicing resulting in two isoforms: one with a shorter and one with a longer form of this exon. This variant is located within both isoforms. This variant is predicted to cause a fr ameshift, which alters the protein?s amino acid sequence beginning at position 1 145 and leads to a premature termination codon 14 amino acids downstream. This a lteration is then predicted to lead to a truncated or absent protein. Frameshift and other loss-of-function variants in DSP have been reported in patients with ARVC and DCM. In summary, although additional studies are required to fully esta blish its clinical significance, the p.Ala1145fs variant is likely pathogenic. A CMG/AMP criteria applied: PVS1, PM2. |