For high confidence predictions that agree with predictions from other methods of VUS reclassification (such as whether it tracks with cancer in tested family members, whether it has been seen with a known deleterious mutation, whether the tumor shows loss of heterozygosity of the wild-type BRCA2 allele, and predictions from cellular functional studies [1, 8, 38]), the protein likelihood ratio (PLR) can aid clinical decision making. The gene discussed is BRCA2; the disease is cancer.