Both sets differ from neutrals (gray dashes). ( B) The L&L variants of severe effect (black line) score higher than intermediates (black dashes).
Nonneutrals are the experimental severe functional effect variants (PMDsevere, black line).
Neutral distributions are represented by the Synonymous (gray line) and the EC sets (thin gray dashes). ( A) Ideally, neutral substitutions should score −100 (vertical gray dashed line) and nonneutrals +100 (vertical black dashed line). Curves were generated using SynergySoftware KaleidaGraph v.4.1.3 smoothing via Stineman function ( 32). In A– E, the right side of the graph is nonneutral and the left side is neutral for all scoring functions. Distribution of variant functional effects.