For a subset of MUTYH disease variants underlying MUTYH-associated polyposis (MAP), also known as familial adenomatous polyposis 2 (FAP2), it was shown that, in addition to impaired catalytic activity, they also exhibit reduced binding to their substrate, adenine mispaired with 8-oxoguanine (OGUA:Ade, also known as 8-oxoG:A). MUTYH alpha-3 isoform (MUTYH-3) mutants with demonstrated deficient binding to OGUA:Ade include missense variants MUTYH-3 Y165C, MUTYH-3 R227W, MUTYH-3 R231L, MUTYH-3 R231H, MUTYH-3 V232F, MUTYH-3 R260Q, MUTYH-3 P281L and MUTYH-3 G382D, and frameshift variants MUTYH-3 Y90fs*, MUTYH-3 Q377fs*, MUTYH-3 E466fs* and MUTYH-3 A368fs26* (commonly known as MUTYH 1103delC) (Chmiel et al. 2003, Parker et al. 2005, Ali et al. 2008, Molatore et al. 2010, D'Agostino et al. 2010).