It is known that different variants of the same tumor predisposition gene can confer different levels of risk and, regarding BRCA1/2 genes, there is robust evidence that the BRCA1 p.Arg1699Gln variant is associated with reduced penetrance of BC and OC, compared to the average (largely truncating) BRCA1 variants.29, 47. Here, BRCA1 is linked to breast cancer.