Utilizing whole exome sequencing, we identified four novel pathogenic variants associated with PFO in the Tibetan population: rs201584759 (c.421C>T: p. R141C) in GABRP, rs200602523 (c.292C>T: p. R98C) in GJB4, rs199568901 (c.5410G>A: E1804K) in RTTN, and rs144768593 (c.5608C>T: p. R1870W) in USH2A. Functional investigations further elucidated the potential roles of GABRP, GJB4, and RTTN in CHD. This evidence concerns the gene RTTN and coronary artery disorder.