ClinVar

Description

The c.752T>C variant in MYOC is a missense variant predicted to cause substitution of Valine by Alanine at amino acid 251 (p.Val251Ala). 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 = 0.839, which met the >= 0.7 threshold for PP3, predicting a damaging effect on MYOC function. 17 segregations in 3 families with juvenile or primary open angle glaucoma (JOAG or POAG), have been reported (PMIDs: 32937162, 23517641 and Pasutto pers. comm.), which fulfilled PP1_Strong (>= 7 meioses in >1 family). 3 probands with JOAG or POAG have been reported carrying this variant (PMIDs: 32937162, 23517641 and Pasutto pers. comm.), which met PS4_Supporting (>= 2 probands). One of these was a confirmed de novo proband with JOAG (PMID: 23517641) (PS2_Moderate). 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, PS2_Moderate, PP3, PS4_Supporting, PM2_Supporting.