Summarizing the RVIS and RVIS-PP2 performance in settings of Online Mendelian Inheritance in Man (OMIM) and Mouse Genome Informatics (MGI) gene lists.

∧Essential gene list was extracted from Georgi et al (2013) [21]. Described in Methods.
*OMIM disease and “haploinsufficient (HI)” gene lists were further filtered. Described in Methods.
#To obtain the presented levels of significance, we used a logistic regression model to regress the presence or absence of a gene, within the corresponding gene list, on the residual variation intolerance score. We provide the corresponding RVIS beta coefficient and its 95% CI.
**A Mann-Whitney U test comparing the RVIS of the corresponding gene list to the remaining non OMIM list genes (n = 14,712 genes). Non OMIM control list was revised For MGI lethality (n = 14,672), MGI seizure (n = 14,660), and Essential gene list (n = 13,179), to exclude genes overlapping with corresponding gene list.