Sig3 captures the different mechanisms associated with underlying HRD in BC, including the biallelic inactivation of BRCA1/2, germline nonsense and frameshift variants in PALB2, missense BRCA1/2 variants known to impair HRR pathway, and the epigenetic silencing of RAD51C and BRCA1 by promoter methylation [125]. This evidence concerns the gene RAD51C and breast cancer.