Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Servicio Canario de Salud, |
RCV003447430 | SCV004174268 | likely pathogenic | Arrhythmogenic right ventricular dysplasia 8 | 2023-06-21 | criteria provided, single submitter | clinical testing | The c.893G>A p.(Trp298Ter) DSP variant has been reported in our laboratory in a 24-year-old female patient with a clinical diagnosis of catecholaminergic ventricular tachycardia. Her father (55 years old), brother (29 years old), uncle (49 years old) and aunt (38 years old) all heterozigous and asymptomatic. This variant has never been reported in DSP related-disorders. Loss-of-function variants in DSP are known to be pathogenic. This variant was absent from large population studies (gnomAD no frequency). In summary, the available evidence for c.893G>A p.(Trp298Ter) DSP variant meets our criteria to be classified as Likely Pathogenic based upon its absence from controls and the clinical correlation in this patient´s phenotype. |
| Ambry Genetics | RCV004364704 | SCV005022682 | pathogenic | Cardiovascular phenotype | 2024-02-05 | criteria provided, single submitter | clinical testing | The p.W298* pathogenic mutation (also known as c.893G>A), located in coding exon 7 of the DSP gene, results from a G to A substitution at nucleotide position 893. This changes the amino acid from a tryptophan to a stop codon within coding exon 7. 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. |