High penetrance genes in HBOC differ from those in CRC; high penetrance genes in CRC are APC, MLH1, MSH2, MSH2/MUTYH, SMAD4, MAP, and APC/PMS2; moderate penetrance genes are MSH6 and PMS2; and low penetrance genes are APC p.I1307K and MUTYH mono-allelic (148). The gene discussed is SMAD4; the disease is colorectal carcinoma.