ClinVar Miner

Submissions for variant NM_000261.2(MYOC):c.761C>T (p.Pro254Leu)

dbSNP: rs2102944853
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Glaucoma Variant Curation Expert Panel RCV001843417 SCV002102561 likely pathogenic Glaucoma of childhood 2022-03-05 reviewed by expert panel curation The c.761C>T variant in MYOC is a missense variant predicted to cause substitution of Proline by Leucine at amino acid 254 (p.Pro254Leu).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 = 0.925, which met the >= 0.7 threshold for PP3, predicting a damaging effect on MYOC function. A previous study (PMID: 35196929) demonstrated that the Pro254Leu 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. A confirmed de novo proband with juvenile open angle glaucoma was identified (PMID: 27080696), meeting PS2_Moderate. However, as this was the only proband identified, the >= 2 probands threshold required to meet PS4_Supporting was not met. 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 juvenile open angle glaucoma based on the ACMG/AMP criteria met, as specified by the ClinGen Glaucoma VCEP (v1, 12 Oct 2021): PS2_Moderate, PS3_Moderate, PP3, PM2_Supporting

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.