Fig. 1

Distribution and computational scores of TUBA1A variants. a TUBA1A domains and localization of variants (missense variants in red, truncating variants in black). Variants above protein scheme are from published data in PubMed, below from databases (ClinVar, DECIPHER, denovo-db). Variants reported ≥3 times (green) and from the cases reported here (blue). While the size of the circle is proportional to the reported frequency, the height is proportional to the CADD-score. b Density plot of all missense variants (pathogenic in red, present in gnomAD in blue). The dashed highlighted grey box indicates the region around Arg402 with significant clustering of pathogenic variants (see Additional file 1: Figure S5). c Generalized additive models of the CADD, M-CAP and REVEL scores for all possible missense variants (see also Additional file 1: Figure S4 A). d Violin- and scatter-plot comparing the three computational scores for missense variants found in two clinical groups of individuals (“clinical review”: 104 cases from literature review and the three cases reported here for a total of 62 distinct variants; “database”: 59 individuals from ClinVar, denovo-db and DECIPHER for a total of 59 variants), healthy controls (“gnomAD”: 9 variants) and all other possible missense variants (“simulated”: 2841 variants) (see also Additional file 1: Figure S4 B)