Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000544613 | SCV000641993 | pathogenic | Arrhythmogenic right ventricular dysplasia 10 | 2023-01-14 | 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: 466348). This variant has not been reported in the literature in individuals affected with DSG2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr207*) 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). |
| Color Diagnostics, |
RCV001805176 | SCV002053347 | uncertain significance | Cardiomyopathy | 2023-10-25 | criteria provided, single submitter | clinical testing | This variant deletes 6 nucleotides in exon 6 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 has been reported in an individual affected with heart failure and suspected of having biventricular arrhythmogenic cardiomyopathy (DOI: 10.26430/CHUNGARICA.2022.52.5.33). This variant was also reported in an individual affected with a syndromic intellectual disability, a congenital heart malformation, and an arrhythmia, and in her mother who had a mild intellectual disability and no apparent cardiovascular disease (PMID: 36360260). 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 DSG2 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. |
| Ambry Genetics | RCV002358510 | SCV002655354 | pathogenic | Cardiovascular phenotype | 2021-06-28 | criteria provided, single submitter | clinical testing | The c.621_626delTCCTCC pathogenic mutation (also known as p.Y207*) is located in coding exon 6 of the DSG2 gene. This pathogenic mutation results from an in-frame TCCTCC deletion at nucleotide positions 621 to 626. This results in the creation of a stop codon at codon 207. 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. |