Here we show that homology models are useful in this setting, a result that significantly increases the number of genes open to structure-based, bioinformatics VUS analysis, including MLH1, MSH2, (hereditary non-polyposis colorectal cancer) ELAC2 (prostate cancer), PALB2 (breast cancer), and NBS1 (breast and prostate cancer). The gene discussed is MSH2; the disease is breast cancer.