Similarly, lack of evidence suggests that probands RESTART_15, RESTART_20, and RESTART_27 do not show symptoms of the severe neurodevelopmental problems typically associated with pathogenic mutations in PRPF8, TRIO, and ZBTB7A. Despite cumulative evidence that the missense variants affect the encoded proteins, additional support such as identifying the same variants in other individuals with a neurodevelopmental disorder or functional validation of an effect on the protein would be needed to fully prove that these variants are pathogenic. Here, PRPF8 is linked to neurodevelopmental disorder.