Fig. 3: Prevalence of technically challenging variants.

For each clinical area, we evaluated the population of pathogenic or likely pathogenic (P/LP) variants that met one or more of our definitions of technically challenging (Fig. 1). Blue bars indicate the prevalence of challenging variants among all reported P/LP findings. The heatmap (green cells) indicates the relative contribution of each variant class to this result. Gray bars indicate the fraction of unique variants that were technically challenging (i.e., when the same variant appeared in more than one patient, it was counted only once in this analysis but was counted multiple times in the prevalence analysis [blue bars]). The differences between these two fractions result from a small number of relatively common P/LP variants that are (e.g., in carrier or neurology testing) or are not (e.g., preventive testing) technically challenging. A total of 102,085 patients with P/LP variants in 1,217 genes are represented in this data set. Challenging variants of most types were observed across clinical areas. CNV copy-number variant, Indel insertion or deletion.