ClinVar

Description

The c.854C>T variant in MYOC is a missense variant predicted to cause substitution of Threonine by Methionine at amino acid 285 (p.Thr285Met). The highest minor allele frequency of this variant was in the Latino/Admixed American population of gnomAD (v3.1.2) = 0.0003273 (5 alleles out of 15,278), which did not meet the PM2_Supporting allele frequency threshold (<=0.0001) or the BS1 allele frequency threshold (>= 0.001). The REVEL score = 0.612, which was neither above nor below the thresholds for PP3 (>= 0.7) or BP4 (<=0.15), predicting a damaging or benign impact on MYOC function. There was no functional evidence predicting a damaging or benign impact of this variant on MYOC function. Only 1 proband with primary open angle glaucoma had been reported (PMID: 12789574), not meeting the >= 2 probands threshold required to meet PS4_Supporting. In summary, this variant did not meet any criteria, receiving a score of 0 and a classification as a variant of uncertain significance (uncertain significance classification range -1 to 5) for primary open angle glaucoma based on the ACMG/AMP criteria met, as specified by the ClinGen Glaucoma VCEP (v1, 12 Oct 2021): none