Abstract
<title>Abstract</title> <p>Background The CanRisk platform provides breast, ovarian and prostate cancer risk predictions on the basis of multiple risk factors including germline variants in nine cancer susceptibility genes. Predictions are dependent on assumptions about the sensitivity of genetic testing and how variants of uncertain significance (VUS) are handled. Methods We propose updated default sensitivities to reflect current testing protocols, using data from large population studies. These sensitivities are based on the assumption that structural variants are typically identified for all genes and that negative tests imply that potentially pathogenic VUS are absent. Results Revised sensitivities result in lower predicted cancer risks for individuals who test negative for pathogenic variants. Conclusions These new default settings have been incorporated into CanRisk and better reflect current clinical usage. Caution is required, however, in using the tool for counselling individuals with potentially pathogenic VUS.</p>