Since the APCDD1 gene has been linked to CRC by being involved in the Wnt signaling pathway as a direct target of the beta-Catenin/TCF4 complex, the associated variant (p.R299H) was prioritized as the top cancer-predisposing candidate of all identified missense variants (Figure 2) [25]. This evidence concerns the gene TCF4 and colorectal carcinoma.