The breast cancer susceptibility gene, BRCA1, is mutated in a high percentage of hereditary breast and ovarian cancers. It is a large gene containing 5,592 nucleotides, and since its discovery over 1,500 distinct mutations have been identified throughout the entire coding region. While genetic screening can be informative it is frustratingly ambiguous, as a complete spectrum of mutation types are presented and, while those that result in the introduction of a premature stop codon or a frame shift can be predicted to adversely affect protein function, there is considerable uncertainty regarding the functional outcome of the majority of the missense mutations. Evaluating the functional significance of such mutations is challenging due to the difficulties in purifying such a large protein. The identification of functional domains in BRCA1 will therefore be critical to the development of functional assays to evaluate their pathogenicity. Prior to our studies only two domains had been identified – the N-terminal RING domain and the C-terminal BRCT domain – and while the structures of both these domains provide a platform from which the structural consequences of missense mutations can be predicted, they only account for 16% of the total protein and hundreds of mutations of unknown pathogenicity remain to be characterised. Our work aims to identify domains in BRCA1 that can be used to determine the functional outcome of missense mutations.