The c.1138G>T variant in MYOC is a missense variant predicted to cause substitution of Aspartic acid by Tyrosine at amino acid 380 (p.Asp380Tyr). This variant was not found in any population of gnomAD (v2.1.1), meeting the ≤ 0.0001 threshold set for PM2_Supporting in a population of at least 10,000 alleles. The REVEL score = 0.964, which met the ≥ 0.7 threshold for PP3, predicting a damaging effect on MYOC function. A previous study (John Hulleman pers. comm., using method described in PMID: 35196929) demonstrated that the Asp380Tyr protein had increased insolubility and reduced secretion levels compared to wild type myocilin protein and met the OddsPath threshold for PS3_Moderate (> 4.3), indicating that this variant did impact protein function. Only 1 proband with primary open angle glaucoma had been reported (PMID: 31302906), not meeting the ≥ 2 probands threshold required to meet PS4_Supporting. Another missense variant (c.1139A>C, p.Asp380Ala, Grantham score = 126, PMID: 9832047) in the same codon has been classified as pathogenic for juvenile open angle glaucoma by the ClinGen Glaucoma VCEP. The c.1138G>T, p.Asp380Tyr variant has a higher Grantham score (= 160) than the previously classified amino acid change, was not predicted to affect splicing as assessed with SpliceAI (≤ 0.2), and met PP3, meeting the conditions for PM5 to apply. In summary, this variant met the criteria to receive a score of 6 and to be classified as likely pathogenic (likely pathogenic classification range 6 to 9) for primary open angle glaucoma based on the ACMG/AMP criteria met, as specified by the ClinGen Glaucoma VCEP (v1, 12 Oct 2021): PM5, PS3_Moderate, PP3, PM2_Supporting.