The c.1496T>G variant in MYOC is a missense variant predicted to cause substitution of Isoleucine by Serine at amino acid 499 (p.Ile499Ser). 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 = 0.798, which met the ≥ 0.7 threshold for PP3, predicting a damaging effect on MYOC function. A previous study (PMID: 11004290) demonstrated that the Ile499Ser protein had increased insolubility levels compared to wild type myocilin protein and met the OddsPath threshold for PS3_Supporting (> 2.1), indicating that this variant did impact protein function. Only 1 segregation had been reported for juvenile open angle glaucoma (JOAG) (PMID: 11004290), not meeting the ≥ 3 segregations required for PP1. Only 1 proband with JOAG had been reported (PMID: 11004290), not meeting the ≥ 2 probands threshold required to meet PS4_Supporting. Another missense variant (c.1495A>T, p.Ile499Phe, Grantham score = 21, PMID: 9328473) in the same codon has been classified as likely pathogenic for JOAG by the ClinGen Glaucoma VCEP. The c.1496T>G, p.Ile499Ser variant has a higher Grantham score (= 142) 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_Supporting to apply. In summary, this variant met the criteria to receive a score of 4 and to be classified as a variant of uncertain significance (uncertain significance classification range -1 to 5) for juvenile open angle glaucoma based on the ACMG/AMP criteria met, as specified by the ClinGen Glaucoma VCEP (v1, 12 Oct 2021): PP3, PS3_Supporting, PM2_Supporting, PM5_Supporting