Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003742625 | SCV000647273 | pathogenic | Familial adenomatous polyposis 1 | 2017-06-21 | criteria provided, single submitter | clinical testing | While this particular variant has not been reported in the literature, loss-of-function variants in APC are known to be pathogenic (PMID: 20685668, 17963004). In addition, multiple truncating variants downstream of this variant have been reported as pathogenic in individuals with familial adenomatous polyposis (PMID: 17064931, 23159591, Invitae). For these reasons, this variant has been classified as Pathogenic. This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the APC gene (p.Thr946Asnfs*9). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1,898 amino acids of the APC protein. |