VCV002498113.1 - ClinVar

NM_000261.2(MYOC):c.1121G>T (p.Gly374Val)

Germline

Top reviewed classifications are shown here.

Submission summary:

1 submission

1 submitter

1 condition

Reviewed by expert panel

Uncertain significance

Apr 2023 by ClinGen Glauco… FDA Recognized Database

for Open-angle glaucoma

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000261.2(MYOC):c.1121G>T (p.Gly374Val)

Variation ID: 2498113 Accession: VCV002498113.1

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 1q24.3 1: 171636319 (GRCh38) [ NCBI UCSC ] 1: 171605459 (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	Apr 15, 2023	Apr 15, 2023	Apr 3, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_000261.2:c.1121G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000252.1:p.Gly374Val	missense
NC_000001.11:g.171636319C>A
NC_000001.10:g.171605459C>A
NG_008859.1:g.21315G>T

Protein change

G374V

Other names

NM_000261.2:c.1121G>T

Canonical SPDI

NC_000001.11:171636318:C:A

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

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	317	345

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.
Open-angle glaucoma	Uncertain significance (1)	reviewed by expert panel	Apr 3, 2023	RCV003219174.1

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 (Apr 03, 2023)	reviewed by expert panel (ClinGen Glaucoma ACMG Specifications v1.1) Method: curation	Open-angle glaucoma (Autosomal dominant inheritance) Affected status: unknown Allele origin: germline	ClinGen Glaucoma Variant Curation Expert Panel FDA Recognized Database Accession: SCV003915540.1 First in ClinVar: Apr 15, 2023 Last updated: Apr 15, 2023	Other databases https://erepo.clinicalgenome.org… https://erepo.clinicalgenome.org/evrepo/ui/interpretation/0e4ca6b6-e46a-473e-8714-7c8602e45f45 Comment: The c.1121G>T variant in MYOC is a missense variant predicted to cause substitution of Glycine by Valine at amino acid 374 (p.Gly374Val). This variant was … (more) The c.1121G>T variant in MYOC is a missense variant predicted to cause substitution of Glycine by Valine at amino acid 374 (p.Gly374Val). 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 = 0.904, 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. 2 probands with primary open angle glaucoma have been reported carrying this variant (PMID: 21552496), which met PS4_Supporting (>= 2 probands). In summary, this variant met the criteria to receive a score of 3 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, PS4_Supporting, PM2_Supporting. (less)

Comment:

The c.1121G>T variant in MYOC is a missense variant predicted to cause substitution of Glycine by Valine at amino acid 374 (p.Gly374Val). 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 = 0.904, 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. 2 probands with primary open angle glaucoma have been reported carrying this variant (PMID: 21552496), which met PS4_Supporting (>= 2 probands). In summary, this variant met the criteria to receive a score of 3 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, PS4_Supporting, 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/0e4ca6b6-e46a-473e-8714-7c8602e45f45	-	-	-	-

Text-mined citations for this variant ...

Record last updated Apr 15, 2023

ClinVar Genomic variation as it relates to human health

NM_000261.2(MYOC):c.1121G>T (p.Gly374Val)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...