ClinVar Miner

Submissions for variant NM_000261.2(MYOC):c.1130C>T (p.Thr377Met)

gnomAD frequency: 0.00004  dbSNP: rs566289099
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 RCV001838869 SCV002098432 pathogenic Glaucoma of childhood 2022-02-20 reviewed by expert panel curation The c.1130C>T variant in MYOC is a missense variant predicted to cause substitution of Threonine by Methionine at amino acid 377 (p.Thr377Met). The highest minor allele frequency of this variant was in the African/African American population of gnomAD (v2.1.1) = 0.00006152 (1 allele out of 16 256), which met the <= 0.0001 threshold set for PM2_Supporting in a population of at least 10,000 alleles. The REVEL score = 0.924, which met the >= 0.7 threshold for PP3, predicting a damaging effect on MYOC function. The studies reporting functional evidence (PMIDs: 11004290, 10545602, 16297911, 16466712) indicated that this variant may impact protein solubility and secretion, however, as the results were conflicting and inconclusive, PS3 was not applied. 47 segregations in 6 families, with juvenile or primary open angle glaucoma (JOAG or POAG), have been reported (PMIDs: 20390039, 11004290, 28564705, 15823921, 12912696), which fulfilled PP1_Strong (>=7 meioses in >1 family). 15 probands with JOAG or POAG have been reported carrying this variant (PMIDs: 28564705, 22933836, 11004290, 12868033, 20390039, 14627955, 10196380, 15823921, 12912696), which met PS4 (>= 15 probands). There were many more probands and families published than presented here. In summary, this variant met the criteria to receive a score of 10 and to be classified as pathogenic (pathogenic classification >= 10) for juvenile open angle glaucoma based on the ACMG/AMP criteria met, as specified by the ClinGen Glaucoma VCEP (v1, 12 Oct 2021): PS4, PP1_Strong, PP3, PM2_Supporting
Laboratory of Medical Genetics, National & Kapodistrian University of Athens RCV003314021 SCV004014013 pathogenic Glaucoma 1, open angle, A 2023-01-31 criteria provided, single submitter clinical testing PS4, PM2, PM5, PP3, PP5

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.