Prophecy or empiricism? Clinical value of predicting versus determining genetic variant functions

The recent explosion of epilepsy genetic testing has created challenges for interpretation of gene variants. Assessments of the functional consequences of genetic variants either by predictive or experimental strategies can contribute to estimating pathogenicity, but there is no consensus on which approach is best. The Special Interest Group on Epilepsy Genetics hosted a session during the Annual American Epilepsy Society Meeting in December 2022 to discuss this topic. The session featured a debate of the relative advantages and limitations of predicting (prophecy) versus experimentally determining (empiricism) variant function using ion channel gene variants as examples. This commentary summarizes these discussions.

Automated summary

The recent increase in epilepsy genetic testing has posed challenges for interpreting gene variants. Assessing the functional effects of genetic variants through predictive or experimental strategies can help determine pathogenicity, but there is no consensus on which approach is optimal. A session during the Annual American Epilepsy Society Meeting in December 2022, hosted by the Special Interest Group on Epilepsy Genetics, discussed the advantages and limitations of predicting (prophecy) versus experimentally determining (empiricism) variant function using ion channel gene variants as examples. This commentary provides an overview of these discussions.