Description
For these reasons, this variant has been classified as Pathogenic. This variant removes the final portion of the C-terminus of the APC protein, including the Basic domain, the EB1 binding site, and the HDLG binding site, which mediate interactions with the cytoskeleton (PMID: 15311282, 17293347). While this variant has not been reported in the literature, different truncations downstream of this variant, p.Asp1942Glufs*27 and p.Asp1979Thrfs*64, have been observed in individuals and families affected with familial adenomatous polyposis and are considered pathogenic (PMID: 20434453, 9824584, 15108286, 11001924). While functional studies have not been performed to directly test the effect of this variant on APC protein function, these observations suggest that deletion of the C-terminal portion of the APC protein is causative of disease. This sequence change inserts 2 nucleotides in exon 16 of the APC mRNA (c.4009_4010dupCT), causing a frameshift at codon 1338. This creates a premature translational stop signal in the last exon of the APC mRNA (p.Gln1338Cysfs*78). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1507 amino acids of the APC protein.
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | germline | unknown | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |
