The CanRisk Tool will sometimes predict a high residual mutation carrier probability when the target (subject of the risk calculation) has had a negative mutation search. This can happen even if the mutation search sensitivities were set to 0.95 (95%). For example, it’s tempting intuitive to think that if the target has had a negative mutation search with the BRCA1/BRCA2 mutation search sensitivities set to 0.95 (95%), then the resulting BRCA1/BRCA2 mutation carrier probabilities should be very small. However, in practice, the mutation search sensitivities reflect the probability of observing a mutation rather than the probability of carrying one. Also, the mutation carrier probabilities predicted by the program are conditional probabilities, which take multiple factors into account. This explains why it’s possible to have a large residual mutation carrier probability under these circumstances.
