Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000549896 | SCV000639733 | pathogenic | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2018-10-09 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in DSP are known to be pathogenic. This particular variant has been reported in the literature in an individual with cardiomyopathy  (PMID: 26735901). This sequence change deletes 1 nucleotide from exon 10 of the DSP mRNA (c.1162delA), causing a frameshift at codon 388. This creates a premature translational stop signal (p.Thr388Leufs*5) and is expected to result in an absent or disrupted protein product. |
| Ambry Genetics | RCV002323971 | SCV002626248 | pathogenic | Cardiovascular phenotype | 2020-12-28 | criteria provided, single submitter | clinical testing | The c.1162delA variant, located in coding exon 10 of the DSP gene, results from a deletion of one nucleotide at nucleotide position 1162, causing a translational frameshift with a predicted alternate stop codon (p.T388Lfs*5). This variant (referred to as chr6:7568034TA>T) has been detected in a peripartum cardiomyopathy cohort (Ware JS et al. N Engl J Med, 2016 Jan;374:233-41). In addition to the clinical data presented in the literature, alterations in DSP that result in haploinsufficiency or protein truncation have been reported in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) and dilated cardiomyopathy (DCM) (Fressart V et al. Europace. 2010;12(6):861-8; Elliott P et al. Circ Cardiovasc Genet. 2010;3(4):314-22; Quarta G et al. Circulation. 2011;123(23):2701-9; Garcia-Pavia P et al. Heart. 2011;97(21):1744-52; Rasmussen TB et al. Clin Genet. 2013;84(1):20-30; Pugh TJ et al. Genet Med. 2014;16(8):601-8). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |