SMAD4 and hereditary cancer: Arguably, the most common concern related to hereditary cancer panel testing is the clinical interpretation of findings in moderate-penetrance genes.23,25 Although clinical management guidelines or consensus opinions exist for the majority of genes included in the panels studied here (APC, BMPR1A, CDH1, MLH1, MSH2, MSH6, MUTYH, PMS2, PTEN, SMAD4, STK11, and TP53), management guidelines are not yet available for the moderate-penetrance genes (ATM, BARD1, BRIP1, CHEK2, MRE11A, NBN, PALB2, RAD50, and RAD51C).