Too few or too many? Variant reporting burden and diagnostic comparisons of an extensive gene panel with exome-sequencing in immunodeficiency

Identifying the underlying etiology of a genetic disease with phenotypic and/or genetic heterogeneity can be tackled using either targeted gene panels or by exome sequencing (ES). Gene panel testing is conducted to thoroughly evaluate all of the genes associated with a phenotype and report all diagnostic, partially diagnostic, and non-diagnostic findings, whereas ES is performed to identify and report diagnostic/partially diagnostic variants tailored to the individual’s phenotype. Historically, gene panels have been deemed most suitable for well-defined phenotypes related to a limited number of genes, while ES has been mostly used for non-specific phenotypes for which little initial speculation could be made about their genetic etiology.