RB1 and cancer: The causal implication of many germline variants in Mendelian diseases has long been recognized (http://omim.org/).5 Numerous cancer predisposing germline variants have also been identified in tumor suppressor genes (TP53, RB), in genes involved in DNA repair (e.g., BRCA1, PALB2, MLH1, MSH2/6, CHEK2, and ATM), cell proliferation (e.g., PTEN, STK11, RET, and FGFR) and cell adhesion (e.g., CDH1, APC).6–9 However, only a small proportion of breast cancer risk can be attributed to high penetrance germline mutations, with each individual SNP contributing only marginally to the risk of cancer.