Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000038084 | SCV000061750 | likely pathogenic | Primary dilated cardiomyopathy | 2012-07-17 | criteria provided, single submitter | clinical testing | The Ile238fs variant in DSP has not been reported in the literature nor previous ly identified by our laboratory. This frameshift variant is predicted to alter t he protein?s amino acid sequence beginning at position 238 and lead to a prematu re termination codon 19 amino acids downstream. This alteration is then predicte d to lead to a truncated or absent protein. In summary, this variant is likely t o be pathogenic, though additional studies are required to fully establish its c linical significance. Please note: Frameshift and nonsense variants in DSP are common in patients with ARVC (http://arvcdatabase.info/), but recent evidence su pports that they can also cause DCM (Elliott 2010, Garcia-Pavia 2011). |
| Invitae | RCV001852799 | SCV002198927 | pathogenic | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2022-02-22 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 44948). This variant has not been reported in the literature in individuals affected with DSP-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ile238Asnfs*19) in the DSP gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DSP are known to be pathogenic (PMID: 20716751, 24503780, 25227139). |
| Ambry Genetics | RCV003362673 | SCV004084108 | pathogenic | Cardiovascular phenotype | 2023-07-22 | criteria provided, single submitter | clinical testing | The c.712dupA variant, located in coding exon 5 of the DSP gene, results from a duplication of A at nucleotide position 712, causing a translational frameshift with a predicted alternate stop codon (p.I238Nfs*19). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |