Fig. 1

Steady-state cellular abundance data for 4721 PTEN variants. A Variants observed in 5 or more replicate in both the original and new PTEN abundance libraries were scored independently and compared. Gray line: ideal correlation with a slope of 1 and intercept of 0. Purple line: Observed correlation with a slope of 0.9 and intercept of 0.1. B Abundance scores for all subsets of variants observed in 4 or more replicates of the combined dataset. C PTEN high-coverage positions with 17 or more scored missense variants were assessed for their mutational tolerance patterns and shown in a clustered heatmap colored by abundance score. Variants that were not scored are colored in gray. WT residues are identified by black dots. Positions were ordered with hierarchical clustering based on their mutational tolerance patterns, with the corresponding dendrogram shown on the bottom. D Ball and stick representations of the Arg173 and Asp326 side chains on the PTEN crystal structure (1d5r), with the hydrogen bonding network at the PTEN inter-domain boundary causing Arg173 and Asp326 to be completely intolerant to substitution. Nitrogen atoms are colored in blue. Oxygen atoms are colored in red. Water molecules are colored in magenta. Predicted hydrogen bonds are denoted as yellow dashed lines. Gly251 is in a turn facing the interdomain interface and is shown at the top of this image