Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000181238 | SCV000233517 | pathogenic | not provided | 2022-07-09 | criteria provided, single submitter | clinical testing | Reported in at least one individual in association with ARVC in published literature (Bhonsale et al., 2015) and other individuals referred for ARVC genetic testing at GeneDx; Frameshift 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 at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25616645, 31589614, 26582918, 31386562) |
Invitae | RCV000799959 | SCV000939651 | pathogenic | Arrhythmogenic right ventricular dysplasia 10 | 2023-08-28 | 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: 199822). This premature translational stop signal has been observed in individual(s) with arrythmogenic right ventricular cardiomyopathy (PMID: 25616645, 31386562). This variant is present in population databases (rs794728091, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Glu156Argfs*14) in the DSG2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DSG2 are known to be pathogenic (PMID: 17105751, 31386562). |
Ambry Genetics | RCV002336442 | SCV002639892 | pathogenic | Cardiovascular phenotype | 2019-05-17 | criteria provided, single submitter | clinical testing | The c.464_465insT pathogenic mutation, located in coding exon 5 of the DSG2 gene, results from an insertion of one nucleotide at position 464, causing a translational frameshift with a predicted alternate stop codon (p.E156Rfs*14). This mutation was identified in 1 individual from an arrhythmogenic right ventricular cardiomyopathy registry (Bhonsale A et al. Eur. Heart J., 2015 Apr;36:847-55). In addition to the clinical data presented in the literature, 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. |