Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000290082 | SCV000330130 | pathogenic | not provided | 2024-05-10 | criteria provided, single submitter | clinical testing | Observed in patients with ARVC referred for genetic testing at GeneDx and in the published literature (PMID: 27532257); 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 a significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 31447099, 31402444, 33087929, 27532257) |
| Labcorp Genetics |
RCV000813935 | SCV000954319 | pathogenic | Arrhythmogenic right ventricular dysplasia 10 | 2024-10-31 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gly166Trpfs*4) 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). This variant is present in population databases (rs781532110, gnomAD 0.008%). This premature translational stop signal has been observed in individual(s) with arrhythmogenic right ventricular cardiomyopathy (PMID: 27532257). ClinVar contains an entry for this variant (Variation ID: 280230). For these reasons, this variant has been classified as Pathogenic. |
| Fulgent Genetics, |
RCV002503975 | SCV002813246 | pathogenic | Arrhythmogenic right ventricular dysplasia 10; Dilated cardiomyopathy 1BB | 2021-11-08 | criteria provided, single submitter | clinical testing | |
| Victorian Clinical Genetics Services, |
RCV000813935 | SCV005398660 | pathogenic | Arrhythmogenic right ventricular dysplasia 10 | 2022-02-02 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0103 - Loss of function and gain of function are reported mechanisms of disease in this gene and are associated with arrhythmogenic right ventricular dysplasia 10 (ARVD; MIM#610193) and dilated cardiomyopathy 1BB (DCM; MIM#612877) (ClinVar, PMID: 23071725). (I) 0112 - The ARVD condition associated with this gene has incomplete penetrance (OMIM). (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0108 - This gene is associated with both recessive and dominant disease. It is commonly associated with dominant inheritance; however recessive inheritance has been reported in severe DCM patients (OMIM). (I) 0304 - Variant is present in gnomAD (v2 & v3) <0.01 (3 heterozygotes, 0 homozygotes). (SP) 0701 - Other NMD predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. Other NMD predicted variants have been reported as pathogenic in ClinVar. (SP) 0803 - This variant has limited previous evidence of pathogenicity in unrelated individuals. This variant has been reported as pathogenic in ClinVar and in an individual with ARVC (PMID: 27532257). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |