Mutational action correlates with morbidity. (A) The action distributions of coding polymorphisms from 218 genes for the 8553 cases that are disease-associated (in black) compared to the 794 that are benign (in gray). Each of these genes, obtained from the UniProt database, is linked to at least one disease. (B) The action distribution of 343 somatic TP53 mutations found frequently in tumor samples (at least ten times in 26,597 cases tallied in the IARC database), compared to (C) the remaining 1026 sporadic TP53 mutations. The fraction with less (more) than 50% of the wild-type transactivation activity in yeast assays is black (white), and those for which these data are unknown is gray. (D) The action distribution of 103 mutations in the CFTR gene binned by the severity of clinical presentation: full-blown cystic fibrosis (top), CFTR-related disorders (middle), and no symptoms (bottom) (Dorfman et al. 2010). Vertical bars indicate median action; numbers refer to the total mutations in each group; box sizes match the quartiles of the distributions, and the error bars indicate the spread of variation. (E) The action distribution of 135 Pompe disease mutations in the GAA gene binned into decreasing severity classes from Class B, the most severe, to Class F, which contains the asymptomatic patients.
