Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000039404 | SCV000063088 | uncertain significance | not specified | 2012-02-13 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Pathogenic. The Thr412fs va riant in DSC2 has been reported in 1 individual with ARVC and 1 affected relativ e (Rajkumar 2012), and was not identified in large population studies. This vari ant has now been identified by our laboratory in 2 individuals with ARVC from on e family (this individual's sons). These individuals carried a second, possibly disease-causing variant, which was also detected in isolation in an affected rel ative. This frameshift variant is predicted to alter the protein?s amino acid se quence beginning at position 412 and lead to a premature termination codon 3 ami no acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function variants in DSC2 are known to be involved in t he etiology of ARVC. Although this data supports that the Thr412fs variant may b e pathogenic, additional studies are needed to fully assess its clinical signifi cance. |
| Gene |
RCV001575584 | SCV001802611 | likely pathogenic | not provided | 2023-10-25 | criteria provided, single submitter | clinical testing | Identified in two siblings with ARVC, however, diagnostic criteria is unclear and functional studies were not performed (PMID: 22458570); 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: 31402444, 22458570) |