Figure 1.

Scheme for the selection of variants used in this study. Functional studies are the gold standard by which to establish the disease association (pathogenic) or normal variation (benign) status of any sequence variant. Unfortunately, functional studies have only been preformed for a small portion of identified variants. To ensure the greatest likelihood that we were using pathogenic and benign variants to examine this series of prediction programs, we used this selection criteria to establish our dataset. Thirty-six additional benign variants were extracted from Ensembl as few had been identified by clinical sequencing analysis. For detailed descriptions of criteria, please see the Materials and Methods section.