VCV002429760.1 - ClinVar

NM_000261.2(MYOC):c.821C>G (p.Pro274Arg)

Germline

Reviewed by expert panel

Reviewed by expert panel. Learn more about how ClinVar calculates review status.

Uncertain significance

for Glaucoma of childhood

Classification is based on the expert panel submission

Feb 2023 by ClinGen Glaucoma Variant Curation Expert Panel

The classification is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

FDA Recognized Database

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000261.2(MYOC):c.821C>G (p.Pro274Arg)

Variation ID: 2429760 Accession: VCV002429760.1

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 1q24.3 1: 171636619 (GRCh38) [ NCBI UCSC ] 1: 171605759 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Feb 18, 2023	Feb 18, 2023	Feb 15, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_000261.2:c.821C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000252.1:p.Pro274Arg	missense
NC_000001.11:g.171636619G>C
NC_000001.10:g.171605759G>C
NG_008859.1:g.21015C>G

Protein change

P274R

Other names

NM_000261.2:c.821C>G

Canonical SPDI

NC_000001.11:171636618:G:C

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA343725980 dbSNP: rs769245094 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
MYOC		-	-	GRCh38 GRCh37	321	349

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Glaucoma of childhood	Uncertain significance (1)	reviewed by expert panel	Feb 15, 2023	RCV003127213.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Uncertain significance (Feb 15, 2023) C Contributing to aggregate classification	reviewed by expert panel (ClinGen Glaucoma ACMG Specifications v1.1) Method: curation	Glaucoma of childhood (Autosomal dominant inheritance) Affected status: unknown Allele origin: germline	ClinGen Glaucoma Variant Curation Expert Panel FDA Recognized Database Accession: SCV003803716.1 First in ClinVar: Feb 18, 2023 Last updated: Feb 18, 2023	Other databases https://erepo.clinicalgenome.org… https://erepo.clinicalgenome.org/evrepo/ui/interpretation/3527af84-9dc5-4a52-913d-7b6245018f62 Comment: The c.821C>G variant in MYOC is a missense variant predicted to cause substitution of Proline by Arginine at amino acid 274 (p.Pro274Arg). This variant was … (more) The c.821C>G variant in MYOC is a missense variant predicted to cause substitution of Proline by Arginine at amino acid 274 (p.Pro274Arg). 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 = 0.949, 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. 6 segregations in 1 family, with juvenile or primary open angle glaucoma (JOAG or POAG), have been reported (PMID: 15255110), which fulfilled PP1_Moderate (5-6 meioses). Only 1 proband with JOAG had been reported (PMID: 15255110), not meeting the >=2 probands threshold required to meet PS4_Supporting. In summary, this variant met the criteria to receive a score of 4 and to be classified 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): PP1_Moderate, PP3, PM2_Supporting (less)

Comment:

The c.821C>G variant in MYOC is a missense variant predicted to cause substitution of Proline by Arginine at amino acid 274 (p.Pro274Arg). 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 = 0.949, 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. 6 segregations in 1 family, with juvenile or primary open angle glaucoma (JOAG or POAG), have been reported (PMID: 15255110), which fulfilled PP1_Moderate (5-6 meioses). Only 1 proband with JOAG had been reported (PMID: 15255110), not meeting the >=2 probands threshold required to meet PS4_Supporting. In summary, this variant met the criteria to receive a score of 4 and to be classified 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): PP1_Moderate, PP3, PM2_Supporting

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/3527af84-9dc5-4a52-913d-7b6245018f62	-	-	-	-

Text-mined citations for rs769245094 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated May 19, 2025

ClinVar Genomic variation as it relates to human health

NM_000261.2(MYOC):c.821C>G (p.Pro274Arg)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs769245094 ...