Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003649354 | SCV001223044 | pathogenic | Familial adenomatous polyposis 1 | 2019-04-19 | criteria provided, single submitter | clinical testing | This variant disrupts the C-terminus of the APC protein. Other variant(s) that disrupt this region (p.Tyr2645Lysfs*14) have been determined to be pathogenic (PMID: 9824584, 1316610, 27081525, 8381579, 22135120, Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with APC-related conditions. This sequence change results in a premature translational stop signal in the APC gene (p.Gln1701*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1143 amino acids of the APC protein. This variant is not present in population databases (ExAC no frequency). |
| Rady Children's Institute for Genomic Medicine, |
RCV003336297 | SCV004046442 | pathogenic | Familial multiple polyposis syndrome | criteria provided, single submitter | clinical testing | This nonsense variant found in exon 15 of 15 is predicted to result in loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay (NMD). This variant has been previously reported as a somatic variant in colorectal cancer (PMID: 29245953). Multiple loss of function variants downstream of the p.Gln1701Ter variant have been reported in affected individuals in the Human Gene Mutation Database (HGMD). It is absent from the gnomAD population database and thus is presumed to be rare. Based on the available evidence, the c.5101C>T (p.Gln1701Ter) variant is classified as Pathogenic. |