In summary, through a comprehensive TBK1 DNA CNVs, MYOC, and OPTN rare variants screening, we (1) discovered 4 novel POAG-associated rare variants, MYOC p.(Cys5Trp), MYOC p.(Thr293Met), OPTN p.(Asn51Thr), and OPTN p.(Gln142His), (2) segregated the OPTN p.(Asn51Thr) variants from an NTG pedigree, and (3) confirmed functional alterations of OPTN p.(Asn51Thr) protein, as well as OPTN p.(Glu50Lys) protein, a well-known causal NTG variant. Here, MYOC is linked to open-angle glaucoma.