MAVE data has already been incorporated into international guidelines for variant interpretation (e.g., for variants in TP53 associated with Li-Fraumeni syndrome [14]) and also has enormous potential in assisting the re-classification variants of unknown significance (e.g., variants in BRCA1 associated with cancer susceptibility [57, 58] and MSH2/MLH1 associated with Lynch syndrome [59, 60]). This evidence concerns the gene MSH2 and cancer.