In Reply We appreciate the interest and comments by Narod, Evans et al, and Blanco et al concerning our recent sequencing study of more than 15 000 women with breast and/or ovarian cancer and unaffected controls.1 The authors raise several points for consideration: interpretation of reported odds ratios (ORs), assessment of our findings for syndromic genes such as NF1 and PTEN, and examination of a specific variant that contributes to our observed association between MSH6 and breast cancer.