Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000792820 | SCV000932141 | pathogenic | Arrhythmogenic right ventricular dysplasia 10 | 2018-10-24 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in DSG2 are known to be pathogenic (PMID: 23381804, 23911551). This variant has not been reported in the literature in individuals with DSG2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Thr291Asnfs*10) in the DSG2 gene. It is expected to result in an absent or disrupted protein product. |
Victorian Clinical Genetics Services, |
RCV000792820 | SCV002769220 | pathogenic | Arrhythmogenic right ventricular dysplasia 10 | 2020-05-21 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene. (N) 0107 - This gene is known to be associated with autosomal dominant disease with reduced penetrance. Digenic inheritance has also been reported (OMIM). (N) 0112 - Variants in this gene are known to have reduced penetrance. (N) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (exon 8 of 15). (P) 0251 - Variant is heterozygous. (N) 0302 - Variant is present in gnomAD <0.001 for a dominant condition. 0.0004% (1/249360) (P) 0701 - Comparable variants have very strong previous evidence for pathogenicity. Almost all frameshift / nonsense variants have been reported as pathogenic / likely pathogenic (ClinVar/DECIPHER). (P) 0803 - Low previous evidence of pathogenicity in unrelated individuals. One patient only has been previously reported (ClinVar). (P) 0905 - No segregation evidence has been identified for this variant. (N) 1007 - No published functional evidence has been identified for this variant. (N) 1208 - Inheritance information for this variant is not currently available. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign |