Submissions for variant NM_000261.2(MYOC):c.271C>T (p.Arg91Ter)

gnomAD frequency: 0.00003  dbSNP: rs143413116

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Glaucoma Variant Curation Expert Panel	RCV002248286	SCV002520334	uncertain significance	Glaucoma of childhood	2022-05-09	reviewed by expert panel	curation	The c.271C>T variant in MYOC is predicted to cause a change in the length of the protein due to the insertion of a terminating codon instead of the usual Arginine at amino acid 91. Truncation of this protein occurs outside of the conserved olfactomedin domain, which did not meet PM4. The highest minor allele frequency of this variant was in the East Asian population of gnomAD (v2.1.1) = 0.0001087 (2 alleles out of 18,394), which did not meet the PM2_Supporting allele frequency threshold (<= 0.0001) or the BS1 allele frequency threshold (>= 0.001). There was no computational or functional evidence predicting a damaging or benign impact of this variant on MYOC function. Only 1 segregation had been reported for juvenile open angle glaucoma (PMID: 24825108), not meeting the >= 3 segregations required for PP1. Although probands with juvenile or primary open angle glaucoma have been reported carrying this variant, PM2_Supporting was not met, therefore PS4 did not apply. 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 juvenile open angle glaucoma based on the ACMG/AMP criteria met, as specified by the ClinGen Glaucoma VCEP (v1, 12 Oct 2021): none
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV005356068	SCV005919716	uncertain significance	Glaucoma 1, open angle, A	2023-01-11	criteria provided, single submitter	research