Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000692450 | SCV000820275 | pathogenic | Hajdu-Cheney syndrome | 2018-03-15 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the NOTCH2 gene (p.Pro2168Glnfs*2). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 302 amino acids of the NOTCH2 protein. This variant has not been reported in the literature in individuals with NOTCH2-related disease. A different truncation (p.Ile2304Hisfs*9) that lies downstream of this variant has been determined to be pathogenic in individuals affected with Hajdu-Cheney syndrome (PMID: 27312922, Invitae). This suggests that deletion of this region of the NOTCH2 protein is causative of disease. For these reasons, this variant has been classified as Pathogenic. |