NM_000104.4(CYP1B1):c.182G>A (p.Gly61Glu) AND Congenital glaucoma

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 31, 2024
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001206715.8

Allele description [Variation Report for NM_000104.4(CYP1B1):c.182G>A (p.Gly61Glu)]

NM_000104.4(CYP1B1):c.182G>A (p.Gly61Glu)

Gene:

CYP1B1:cytochrome P450 family 1 subfamily B member 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p22.2

Genomic location:

Preferred name:

NM_000104.4(CYP1B1):c.182G>A (p.Gly61Glu)

HGVS:

NC_000002.12:g.38075207C>T
NG_008386.2:g.5895G>A
NM_000104.4:c.182G>AMANE SELECT
NP_000095.2:p.Gly61Glu
NP_000095.2:p.Gly61Glu
NC_000002.11:g.38302350C>T
NM_000104.3:c.182G>A
Q16678:p.Gly61Glu

Protein change:

G61E; GLY61GLU

Links:

UniProtKB: Q16678#VAR_001244; OMIM: 601771.0003; dbSNP: rs28936700

NCBI 1000 Genomes Browser:

rs28936700

Molecular consequence:

NM_000104.4:c.182G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Congenital glaucoma
Identifiers:: MONDO: MONDO:0020366; MedGen: C0020302

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001378037	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 31, 2024)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 9463332, 12372064, 19234632, 18470941, 19793111, 27243976, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001378037

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 31, 2024)

germline

clinical testing

PubMed (7)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in CYP1B1, the gene for cytochrome P4501B1, are the predominant cause of primary congenital glaucoma in Saudi Arabia.

Bejjani BA, Lewis RA, Tomey KF, Anderson KL, Dueker DK, Jabak M, Astle WF, Otterud B, Leppert M, Lupski JR.

Am J Hum Genet. 1998 Feb;62(2):325-33.

PubMed [citation]

PMID:: 9463332
PMCID:: PMC1376900

A novel frameshift founder mutation in the cytochrome P450 1B1 (CYP1B1) gene is associated with primary congenital glaucoma in Morocco.

Belmouden A, Melki R, Hamdani M, Zaghloul K, Amraoui A, Nadifi S, Akhayat O, Garchon HJ.

Clin Genet. 2002 Oct;62(4):334-9.

PubMed [citation]

PMID:: 12372064

See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001378037.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 61 of the CYP1B1 protein (p.Gly61Glu). This variant is present in population databases (rs28936700, gnomAD 0.04%), including at least one homozygous and/or hemizygous individual. This missense change has been observed in individuals with primary congenital glaucoma (PMID: 9463332, 12372064, 19234632). It is commonly reported in individuals of Saudi and Moroccan ancestry (PMID: 9463332, 12372064, 19234632). This variant is also known as c.3987G>A. ClinVar contains an entry for this variant (Variation ID: 7730). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CYP1B1 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects CYP1B1 function (PMID: 18470941, 19793111, 27243976). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Oct 20, 2024

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