Although SNAP was extensively cross-validated, we also evaluated performance on additional data sets that have previously been used for benchmarking. These were the mutagenesis data for LacI repressor from Escherichia coli (32 (link)), bacteriophage T4 lysozyme (33 (link)), and HIV-1 protease (34 (link)). This additional data set, that has been used previously in evaluation of other tools (14 (link)), and methods (16 (link),27 (link)), consisted of 4041 LacI mutants, 2015 Lysozyme mutants, and 336 HIV-1 protease mutants; effects were classified by: very damaging, damaging, slightly damaging, neutral. In order to evaluate the performance of SNAP in comparison to SNPs3D (17 (link)), a tool aimed at resolving effects of human nsSNPs, we utilized a set of 45 non-neutral mutants of the human melanocortin-4 receptor (C. Vaisse, personal communication). All SNAP predictions for these sets (and those currently made by the server) were obtained by averaging outputs of ten different networks trained on split PMD/EC data as described in the cross-validation procedure above.