Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000603286 | SCV000711722 | uncertain significance | not specified | 2017-12-07 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Pathogenic. The p.Thr371fs variant in DSG2 has not been previously reported in individuals with cardiomyopa thy and was absent from large population studies. This variant is predicted to c ause a frameshift, which alters the protein?s amino acid sequence beginning at p osition 371 and leads to a premature termination codon 19 amino acids downstream . This alteration is then predicted to lead to a truncated or absent protein. Fr ameshift and other loss of function variants in DSG2 gene have been reported in individuals with ARVC. In summary, while there is some suspicion for a pathogeni c role, the clinical significance of the p.Thr371fs variant is uncertain. |
| Gene |
RCV001561033 | SCV001783553 | likely pathogenic | not provided | 2024-06-03 | criteria provided, single submitter | clinical testing | Reported in an individual undergoing whole exome sequencing in published literature; although the indications for testing and follow-up cardiac evaluations were not described (PMID: 30122538); 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: 30122538) |
| All of Us Research Program, |
RCV004002477 | SCV004816642 | uncertain significance | Arrhythmogenic right ventricular cardiomyopathy | 2023-04-03 | criteria provided, single submitter | clinical testing | This variant inserts 1 nucleotide in exon 9 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. To our knowledge, this variant has not been reported in individuals affected with cardiovascular disorders in the literature. 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 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. |
| Fulgent Genetics, |
RCV005019031 | SCV005652435 | likely pathogenic | Arrhythmogenic right ventricular dysplasia 10; Dilated cardiomyopathy 1BB | 2024-01-05 | criteria provided, single submitter | clinical testing |