ClinVar Miner

Submissions for variant NM_000261.2(MYOC):c.1091G>T (p.Gly364Val)

dbSNP: rs121909193
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Glaucoma Variant Curation Expert Panel RCV001838522 SCV002098430 likely pathogenic Glaucoma of childhood 2022-02-20 reviewed by expert panel curation The c.1091G>T variant in MYOC is a missense variant predicted to cause substitution of Glycine by Valine at amino acid 364 (p.Gly364Val). 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 = 0.896, which met the >= 0.7 threshold for PP3, predicting a damaging effect on MYOC function. A previous study (PMID: 16466712) demonstrated that the Gly364Val protein had 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. 18 segregations in 2 families, with juvenile or primary open angle glaucoma (JOAG or POAG), have been reported (PMID: 9535666), which fulfilled PP1_Strong (>=7 meioses in >1 family). 2 probands with JOAG or POAG have been reported carrying this variant (PMID: 10196380), which met PS4_Supporting (>= 2 probands). In summary, this variant met the criteria to receive a score of 9 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): PP1_Strong, PS3_Moderate, PP3, PS4_Supporting, PM2_Supporting
OMIM RCV000008410 SCV000028618 pathogenic Glaucoma 1, open angle, A 2018-11-07 no assertion criteria provided literature only

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.