Submissions for variant NM_000261.2(MYOC):c.227G>A (p.Arg76Lys)

gnomAD frequency: 0.09970  dbSNP: rs2234926

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Glaucoma Variant Curation Expert Panel	RCV001843356	SCV002102558	benign	Glaucoma of childhood	2022-03-05	reviewed by expert panel	curation	The c.227G>A variant in MYOC is a missense variant predicted to cause substitution of Arginine by Lysine at amino acid 76 (p.Arg76Lys). The highest minor allele frequency of this variant was in the South Asian population of gnomAD (v2.1.1) = 0.3468, which met the >= 0.01 threshold set for BA1 (10,613 alleles out of 30,602, meeting the threshold of >= 5 of at least 2,000 observed alleles). The REVEL score = 0.203, 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. Previous studies (PMIDs: 16466712 and 35196929) demonstrated that the Arg76Lys protein had similar solubility and secretion levels to wild type myocilin protein and met the OddsPath threshold for BS3_Moderate (< 0.23), indicating that this variant did not impact protein function. As BA1 was met, PP1 did not apply and segregations were not counted. 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 was classified as benign (BA1 is a stand-alone criterion for a benign level of pathogenicity) for juvenile open angle glaucoma based on the ACMG/AMP criteria met, as specified by the ClinGen Glaucoma VCEP (v1, 12 Oct 2021): BA1, BS3_Moderate.
Eurofins Ntd Llc (ga)	RCV000173089	SCV000224173	benign	not specified	2014-06-10	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000173089	SCV000303316	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000316846	SCV000351307	likely benign	Glaucoma	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000371420	SCV000351308	likely benign	Glaucoma 1, open angle, A	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
CeGaT Center for Human Genetics Tuebingen	RCV000994193	SCV001147545	uncertain significance	not provided	2016-10-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000994193	SCV001884827	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 18449353, 17361544, 28792703, 22449891, 15025728, 27884173, 21168818, 23029558, 14688426, 23517641, 16466712)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000994193	SCV002322584	benign	not provided	2024-01-22	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000994193	SCV005288492	benign	not provided		criteria provided, single submitter	not provided