In addition to multiple loci, it appears to be a general feature of most populations that there are a large number of different highly penetrant mutations in any given disease susceptibility gene; In BRCA2 for example, at least 2000 distinct pathogenic mutations have been reported, along with ∼800 other sequence variants whose pathogenicity is still uncertain (Breast Cancer Information Core database [8]). The gene discussed is BRCA2; the disease is breast carcinoma.