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NM_000261.2(MYOC):c.1447G>T (p.Glu483Ter) AND Open-angle glaucoma

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Apr 3, 2023
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV003219168.1

Allele description [Variation Report for NM_000261.2(MYOC):c.1447G>T (p.Glu483Ter)]

NM_000261.2(MYOC):c.1447G>T (p.Glu483Ter)

Gene:
MYOC:myocilin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q24.3
Genomic location:
Preferred name:
NM_000261.2(MYOC):c.1447G>T (p.Glu483Ter)
Other names:
NM_000261.2:c.1447G>T
HGVS:
  • NC_000001.11:g.171635993C>A
  • NG_008859.1:g.21641G>T
  • NM_000261.2:c.1447G>TMANE SELECT
  • NP_000252.1:p.Glu483Ter
  • NC_000001.10:g.171605133C>A
Protein change:
E483*
Molecular consequence:
  • NM_000261.2:c.1447G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Open-angle glaucoma
Identifiers:
MONDO: MONDO:0005338; MedGen: C0017612; Human Phenotype Ontology: HP:0012108

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003915532ClinGen Glaucoma Variant Curation Expert Panel
reviewed by expert panel

(ClinGen Glaucoma ACMG Specifications v1.1)		Uncertain significance
(Apr 3, 2023) 		germlinecuration

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Details of each submission

From ClinGen Glaucoma Variant Curation Expert Panel, SCV003915532.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The c.1447G>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 Methionine at amino acid 483. This variant is predicted to cause a deletion of < 10% of the protein within the conserved olfactomedin domain, meeting PM4_Supporting. 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. There was no computational or 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: 10196380), 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): PM2_Supporting, PM4_Supporting.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Apr 15, 2023