Submissions for variant NM_000261.2(MYOC):c.974C>T (p.Thr325Met)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Glaucoma Variant Curation Expert Panel	RCV002509857	SCV002818485	uncertain significance	Glaucoma 1, open angle, E	2022-12-14	reviewed by expert panel	curation	The c.974C>T variant in MYOC is a missense variant predicted to cause substitution of Threonine by Methionine at amino acid 325 (p.Thr325Met). The highest minor allele frequency of this variant was in the South Asian population of gnomAD (v2.1.1) = 0.00006536 (2 alleles out of 30,602), which met the <=0.0001 threshold set for PM2_Supporting in a population of at least 10,000 alleles. The REVEL score = 0.777, which met the >= 0.7 threshold for PP3, predicting a damaging effect 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: 24825108), not meeting the >= 2 probands threshold required to meet PS4_Supporting. In summary, this variant met the criteria to receive a score of 2 and to be classified 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): PP3, PM2_Supporting.