Towards Increasing the Clinical Relevance of In Silico Methods to Predict Pathogenic Missense Variants
Fig 2
Some advantages of considering endophenotypes, relative to phenotypes, illustrated using three CFTR variants.
Mean sweat chloride from individuals harboring the three variants (S1235R, D614G, and G551D), and results from two distinct in vivo experiments performed in cells expressing the variants. Increasing sweat chloride is associated with increasing disease severity, whereas in the two in vivo assays decreasing values correspond to decreasing protein function or abundance. Endophenotypes were scaled for purposes of presenting on a single chart, such that three sweat chlorides could be compared with one another, the three chloride conductance measurements could be compared with one another, etc.