The APC gene encodes a tumor suppressor protein that acts as an antagonist of the Wnt signaling pathway. APC promotes rapid degradation of beta-catenin and participates in Wnt signaling as a negative regulator. APC is also involved in other processes including cell migration, cell adhesion, transcriptional activation and apoptosis. Germline defects in this gene cause familial adenomatous polyposis (FAP), an autosomal dominant pre-malignant disease that usually progresses to malignancy. Somatic mutations in APC have been reported in around 2% of breast carcinomas. One study found that APC mutations in up to 18% of their breast cancer cohort and at a significantly high frequency in advanced stages of primary breast cancers. The APC K1454E variant has not been previously reported in breast carcinoma. The significance of this variant should be interpreted within the clinical context.

The APC gene encodes a tumor suppressor protein that acts as an antagonist of the Wnt signaling pathway. APC promotes rapid degradation of beta-catenin and participates in Wnt signaling as a negative regulator. Germline defects in this gene cause familial adenomatous polyposis (FAP), an autosomal dominant pre-malignant disease that usually progresses to malignancy. Somatic mutations in APC have been reported in 4% of lung adenocarcinomas, the prognostic and therapeutic implications of which remain to be fully elucidated. APC K1454E lies within the beta-catenin binding and down-regulation region of the Apc protein. K1454E suppresses beta-catenin mediated transcription at a level similar to wild-type Apc in a cell culture assay and therefore, is predicted to have no effect on Apc protein function. This variant has also been reported as a germline variant in prior studies and reported in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/RCV000200964/) as likely benign.