Fig. 3: Distribution of the PAX6 missense variants included in this study.
From: Using computational approaches to enhance the interpretation of missense variants in the PAX6 gene
Variant distribution according to their pathogenicity is shown. The X-axis represents the PAX6 canonical protein sequence (422 amino acids), while the Y-axis denotes the number of variants impacting the same residue. A difference can be noted in the clustering patterns of the presumed neutral variants between the primary and secondary datasets (b compared to e). In the latter, the number of variants that are found to be altering amino acids in the DNA-binding domains is greater and this could potentially reflect the more diverse ancestral backgrounds and phenotypic profiles of the individuals included in the BRAVO dataset compared to those included in the gnomAD controls/biobanks cohorts. Green bar, paired domain; red bar, homeodomain. DM?, “likely disease-causing mutation with questionable pathogenicity” (as assigned in the Human Gene Mutation Database [HGMD]); VUS variants of uncertain significance. BRAVO denotes the TOPMed (Trans-Omics for Precision Medicine) Data Freeze 8 while gnomAD denotes Genome Aggregation Database v2 and v3 (controls/biobanks subsets).
