Scaling national and international improvement in virtual gene panel curation via a collaborative approach to discordance resolution

Clinical validity assessments of gene-disease associations underpin analysis and reporting in diagnostic genomics, and yet wide variability exists in practice, particularly in use of these assessments for virtual gene panel design and maintenance. Harmonization efforts are hampered by the lack of agreed terminology, agreed gene curation standards, and platforms that can be used to identify and resolve discrepancies at scale. We undertook a systematic comparison of the content of 80 virtual gene panels used in two healthcare systems by multiple diagnostic providers in the United Kingdom and Australia. The process was enabled by a shared curation platform, PanelApp, and resulted in the identification and review of 2,144 discordant gene ratings, demonstrating the utility of sharing structured gene-disease validity assessments and collaborative discordance resolution in establishing national and international consensus.

Automated summary

A systematic comparison of 80 virtual gene panels used by multiple diagnostic providers in the UK and Australia was conducted, resulting in the identification and review of 2,144 discordant gene ratings using the shared curation platform PanelApp. This study highlights the utility of sharing structured gene-disease validity assessments and collaborative discordance resolution in establishing national and international consensus.