In the Ashkenazi Jewish population, Shaag et al [14] discovered the novel missense mutation S428F (1283C>T) at a frequency of 2.88% amongst 1632 breast cancer patients compared to 1.37% of 1673 controls, thus suggesting S428F is associated with breast cancer risk; a yeast complementation assay supported the hypothesis that this variant aberrantly affects CHEK2 protein function. The gene discussed is CHEK2; the disease is breast carcinoma.