APC and Familial adenomatous polyposis: Nevertheless, over 20% of classical FAP and up to 80% of AFAP patients remain APC mutation-negative, which may be attributable to methodological shortcomings in association with particular types of mutations [5–8], nontruncating alterations with uncertain pathogenic significance [2], and susceptibility associated with other genes than APC, such as MUTYH [3], POLE and POLD [9], and AXIN2 [10].