Fig. 3

Genetic diagnosis of the DSD cohort. a Proportion of 46,XY DSD patients with a curated variant in a known DSD gene. In 46,XY DSD patients (278 patients), a DSD variant was identified in 57% (159 patients) of the study cohort. This was made up of 76 pathogenic variants and 42 likely pathogenic variants, resulting in a diagnostic rate of 43%. A total of 41 VUS were also found. b In the 46,XX DSD patient cohort (48), only 19% (9) were found to have a variant in a DSD gene, most of which were SRY translocations (8). This resulted in a diagnostic rate of 17%. c Distribution of curated variants in DSD genes among the 46,XY DSD phenotypic categories. Variants in a diagnostic DSD gene found to be pathogenic or likely pathogenic are considered to be a genetic diagnosis. The diagnostic outcome for each of the phenotypic categories is indicated. Disorders of gonadal (testicular) development patients had a total of 21 out of 52 patients with a pathogenic or likely pathogenic DSD variant (40%) and only two patients with a VUS (4%). Of the patients with a suspected disorder of androgen synthesis and action, 22 patients of 37 had a diagnostic variant (60%) and four had a VUS (10%). Of patients in the 46,XY other category (including hypospadias), just 18 out of 56 had a diagnostic variant (32%), with 11 patients having a VUS (19%). Finally, in the broad category 46,XY DSD unknown, which includes 133 patients, 57 had a pathogenic or likely pathogenic (43%) variant, while 24 patients had a VUS (18%). In cases where a patient had variants in multiple genes, the variant with the highest classification (pathogenic > likely pathogenic > VUS) was taken into consideration for this chart