Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000039448 | SCV000063132 | likely pathogenic | Arrhythmogenic right ventricular cardiomyopathy | 2017-05-18 | criteria provided, single submitter | clinical testing | proposed classification - variant undergoing re-assessment, contact laboratory |
CHEO Genetics Diagnostic Laboratory, |
RCV000769504 | SCV000900899 | likely pathogenic | Cardiomyopathy | 2017-01-30 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001824284 | SCV002073980 | likely pathogenic | not provided | 2023-01-13 | criteria provided, single submitter | clinical testing | Reported in association with ARVC/D; however, at least one patient also harbored a second missense variant in the DSC2 gene and detailed clinical information was not provided (Barahona-Dussault et al., 2010; Adler et al., 2016); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (gnomAD); Reported in ClinVar (ClinVar Variant ID#46204); This variant is associated with the following publications: (PMID: 31402444, 23911551, 19863551, 26743238) |
Invitae | RCV001781362 | SCV002228633 | pathogenic | Arrhythmogenic right ventricular dysplasia 11 | 2023-09-03 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Cys32*) in the DSC2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DSC2 are known to be pathogenic (PMID: 23911551). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with arrhythmogenic right ventricular cardiomyopathy (PMID: 19863551). ClinVar contains an entry for this variant (Variation ID: 46204). For these reasons, this variant has been classified as Pathogenic. |
Ai |
RCV001824284 | SCV002502759 | likely pathogenic | not provided | 2021-10-05 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV003338394 | SCV004058117 | likely pathogenic | Cardiovascular phenotype | 2023-09-14 | criteria provided, single submitter | clinical testing | The c.96delC variant, located in coding exon 2 of the DSC2 gene, results from a deletion of one nucleotide at nucleotide position 96, causing a translational frameshift with a predicted alternate stop codon (p.C32*). The predicted stop codon occurs in the 5’ end of theDSC2 gene. Premature termination codons in the 5’ end of a gene have been reported to escape nonsense-mediated mRNAdecay and/or lead to re-initiation (Rivas et al. Science. 2015 May 8;348(6235):666-9; Lindeboom et al. Nat Genet. 2016 Oct;48(10):1112-8; Rhee et al. Sci Rep. 2017 May 10;7(1):1653). Direct evidence for this alteration is unavailable, however premature termination codons are typically deleterious in nature. This variant has been detected in individuals from an arrhythmogenic right ventricular cardiomyopathy cohort (Adler A et al. Circ Arrhythm Electrophysiol, 2016 Jan;9:e003440). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
Preventiongenetics, |
RCV003398606 | SCV004103535 | likely pathogenic | DSC2-related condition | 2023-01-31 | criteria provided, single submitter | clinical testing | The DSC2 c.96delC variant is predicted to result in premature protein termination (p.Cys32*). This variant has been reported in individuals with arrhythmogenic right ventricular dysplasia and cardiomyopathy (Barahona-Dussault et al. 2010. PubMed ID: 19863551; Ye et al. 2019. PubMed ID: 31402444). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Early termination variants in DSC2 are expected to be pathogenic. This variant is interpreted as likely pathogenic. |