Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000181248 | SCV000233527 | likely pathogenic | not provided | 2024-06-03 | criteria provided, single submitter | clinical testing | Variant, reported as c.915G>A (W305X) using alternate nomenclature, was observed in the compound heterozygous state with DSG2 p.(R48H) in an individual with ARVC, as well as in the heterozygous state in two unaffected relatives (PMID: 16773573); Observed in an individual with ARVC (PMID: 31386562); Not observed at significant frequency in large population cohorts (gnomAD); 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; This variant is associated with the following publications: (PMID: 20857253, 25525159, 20031617, 31402444, 16773573, 31386562) |
| Labcorp Genetics |
RCV000018304 | SCV002232679 | pathogenic | Arrhythmogenic right ventricular dysplasia 10 | 2023-07-31 | 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: 16811). This variant is also known as W305X. This premature translational stop signal has been observed in individual(s) with arrhythmogenic right ventricular dysplasia/cardiomyopathy (PMID: 16773573). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp306*) 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). |
| MGZ Medical Genetics Center | RCV000018304 | SCV002580542 | likely pathogenic | Arrhythmogenic right ventricular dysplasia 10 | 2021-12-28 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV002496397 | SCV002807758 | likely pathogenic | Arrhythmogenic right ventricular dysplasia 10; Dilated cardiomyopathy 1BB | 2021-11-25 | criteria provided, single submitter | clinical testing | |
| Kardio |
RCV000018304 | SCV004809101 | likely pathogenic | Arrhythmogenic right ventricular dysplasia 10 | 2024-03-14 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV003996106 | SCV004842775 | uncertain significance | Arrhythmogenic right ventricular cardiomyopathy | 2023-12-18 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 8 of the DSG2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant (referred to as c.915G>A, W305X) has been reported in an individual affected with arrhythmogenic right ventricular cardiomyopathy, who also carried another pathogenic variant in the DSG2 gene that could explain the observed phenotype (PMID: 16773573). This variant has been observed in the proband's unaffected mother and sister as well. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Although there is a suspicion for a pathogenic role, clinical relevance of loss-of-function DSC2 truncation and splice 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. |
| OMIM | RCV000018304 | SCV000038583 | pathogenic | Arrhythmogenic right ventricular dysplasia 10 | 2006-07-01 | no assertion criteria provided | literature only |