Figure 4.

Flowchart suggesting clinical use for Protein Likelihood Ratio (PLR). “Variant of Undetermined Significance” (VUS) is one of 3 possible results in BRCA genetic testing [43]. The PLR, when it is a high confidence prediction, and when it agrees with other data predicting whether a VUS is deleterious or neutral, can classify VUS as neutral or deleterious. Neutral VUS can be treated as if BRCA testing was negative, and deleterious VUS can be treated as if BRCA testing was positive. Other data potentially available to compare with VUS predictions include: 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].