BRCA1 and cancer: The joint analysis described here provides the basis to assess the extent to which we can use variant annotation in one protein domain (i.e., BRCT domains of the BRCA1 protein) to annotate variants in other genes coding for proteins containing BRCT domains that are critical for the cellular response to DNA damage25,26 with implications for cancer predisposition (e.g., BRCA1, BARD1 and NBN) and therapy (e.g., PARP1).