For pleomorphic syndromic phenotypes, it is only feasible to estimate MTAFpred by pulling out a specific component of the syndrome and estimating the frequency, penetrance, and genetic heterogeneity for this component (eg, type 2 renal papillary cancer for the FH gene [hereditary leiomyomatosis and renal cell carcinoma] or medullary thyroid cancer for the RET gene [multiple endocrine neoplasia type 2]).27 Here, FH is linked to hereditary clear cell renal cell carcinoma.