Po-629-02 new evidence to challenge clingen's “disputed evidence” designation for akap9 as a bona fide susceptibility gene for congenital long qt syndrome

A-kinase-anchoring protein-9 (AKAP9) mediates the phosphorylation state of the KCNQ1-encoded Kv7.1 potassium channel. Loss-of-function (LOF) variants in KCNQ1 cause type 1 long QT syndrome (LQT1). In 2007, we published data suggesting AKAP9-S1570L as a novel LQTS-causative variant and AKAP9 as a novel LQTS-susceptibility gene. However, in a recent re-appraisal of LQTS genes, the Clinical Genome Resource (ClinGen) demoted AKAP9 to a “disputed evidence” gene due to apparent lack of sufficient evidence to support causation of LQTS.