NM_000261.2(MYOC):c.1267A>G (p.Lys423Glu) AND Glaucoma 1, open angle, A

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 1, 1998
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000008417.5

Allele description [Variation Report for NM_000261.2(MYOC):c.1267A>G (p.Lys423Glu)]

NM_000261.2(MYOC):c.1267A>G (p.Lys423Glu)

Gene:

MYOC:myocilin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q24.3

Genomic location:

Preferred name:

NM_000261.2(MYOC):c.1267A>G (p.Lys423Glu)

Other names:

NM_000261.2(MYOC):c.1267A>G

HGVS:

NC_000001.11:g.171636173T>C
NG_008859.1:g.21461A>G
NM_000261.2:c.1267A>GMANE SELECT
NP_000252.1:p.Lys423Glu
NC_000001.10:g.171605313T>C
Q99972:p.Lys423Glu

Protein change:

K423E; LYS423GLU

Links:

UniProtKB: Q99972#VAR_009689; OMIM: 601652.0010; dbSNP: rs74315336

NCBI 1000 Genomes Browser:

rs74315336

Molecular consequence:

NM_000261.2:c.1267A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Glaucoma 1, open angle, A (GLC1A)
Synonyms:: Primary open angle glaucoma juvenile onset 1; Glaucoma hereditary, juvenile; Glaucoma, Dominant (Juvenile Onset)
Identifiers:: MONDO: MONDO:0007664; MedGen: C1842028; Orphanet: 98977; OMIM: 137750

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000028625	OMIM	no assertion criteria provided	Pathogenic (Aug 1, 1998)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 9697688, 6770678

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000028625

OMIM

no assertion criteria provided

Pathogenic
(Aug 1, 1998)

germline

literature only

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Homozygotes carrying an autosomal dominant TIGR mutation do not manifest glaucoma.

Morissette J, Clépet C, Moisan S, Dubois S, Winstall E, Vermeeren D, Nguyen TD, Polansky JR, Côté G, Anctil JL, Amyot M, Plante M, Falardeau P, Raymond V.

Nat Genet. 1998 Aug;19(4):319-21. No abstract available.

PubMed [citation]

PMID:: 9697688

Metabolic interference and the + - heterozygote. a hypothetical form of simple inheritance which is neither dominant nor recessive.

Johnson WG.

Am J Hum Genet. 1980 May;32(3):374-86.

PubMed [citation]

PMID:: 6770678
PMCID:: PMC1686061

Details of each submission

From OMIM, SCV000028625.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

In a French Canadian family with primary open angle glaucoma (POAG; 137750), Morissette et al. (1998) identified an A-to-G transition at nucleotide 1332 of the MYOC gene, resulting in a change of glutamic acid for lysine at codon 423 (K423E). Four adult homozygotes were asymptomatic, with POAG affecting only the heterozygotes. Morissette et al. (1998) stated that the K423E mutation appeared to be the first mutation that caused an autosomal dominant heterozygote-specific disease phenotype in humans. This may be an example of the situation hypothesized by Johnson (1980) and termed metabolic interference or negative complementation.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 24, 2022

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