Total submissions: 4
| 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) |
| Labcorp Genetics |
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. |
| All of Us Research Program, |
RCV003996625 | SCV004830611 | uncertain significance | Arrhythmogenic right ventricular cardiomyopathy | 2023-04-10 | criteria provided, single submitter | clinical testing | This variant inserts 1 nucleotide in exon 5 of the DSG2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in individual(s) affected with arrhythmogenic right ventricular dysplasia/cardiomyopathy (PMID: 25616645, 31386562). This variant has been identified in 1/249316 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Although there is a suspicion for a pathogenic role, clinical significance of loss-of-function DSG2 variants in autosomal dominant arrhythmogenic cardiomyopathy is not yet clearly established. The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |