Evaluation of the severity of variants’ pathogenicity. We used a combined annotation dependent depletion score (CADD), a tool for scoring the deleteriousness of genetic variants, with cutoff of >20³¹ to determine the effect of variant severity, among the 3 genetic variants categories. They were including predicted variants (n = 618), previously reported variants that were identified in gnomAD (n = 140), and the 153 variants that have been reported to cause hTTP in the literature but were not found in gnomAD. This figure also shows the distribution of the CADD score among them, with no significant differences between these 3 groups.