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NM_000404.4(GLB1):c.1769G>A (p.Arg590His)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely pathogenic(1);Pathogenic(1);Uncertain significance(1)

Review status:
criteria provided, conflicting interpretations
Submissions:
3 (Most recent: Jan 7, 2021)
Last evaluated:
Oct 23, 2020
Accession:
VCV000092901.5
Variation ID:
92901
Description:
single nucleotide variant
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NM_000404.4(GLB1):c.1769G>A (p.Arg590His)

Allele ID
98808
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
3p22.3
Genomic location
3: 32997310 (GRCh38) GRCh38 UCSC
3: 33038802 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000003.11:g.33038802C>T
NC_000003.12:g.32997310C>T
NG_009005.1:g.104893G>A
... more HGVS
Protein change
R590H, R638H, R459H, R560H
Other names
-
Canonical SPDI
NC_000003.12:32997309:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD) 0.00003
The Genome Aggregation Database (gnomAD), exomes 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
Links
ClinGen: CA201251
dbSNP: rs398123351
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 1 criteria provided, single submitter Nov 6, 2013 RCV000174999.2
Uncertain significance 1 criteria provided, single submitter May 22, 2018 RCV000674722.1
Likely pathogenic 1 criteria provided, single submitter Oct 23, 2020 RCV000794211.3
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
GLB1 - - GRCh38
GRCh37
466 508

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(May 22, 2018)
criteria provided, single submitter
Method: clinical testing
Infantile GM1 gangliosidosis
GM1 gangliosidosis type 2
GM1 gangliosidosis type 3
Mucopolysaccharidosis, MPS-IV-B
Allele origin: unknown
Counsyl
Accession: SCV000800111.1
Submitted: (Jul 10, 2018)
Evidence details
Publications
PubMed (3)
Pathogenic
(Nov 06, 2013)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000226418.5
Submitted: (Jun 30, 2017)
Evidence details
Other databases
http://www.egl-eurofins.com/emvc…
Likely pathogenic
(Oct 23, 2020)
criteria provided, single submitter
Method: clinical testing
Mucopolysaccharidosis, MPS-IV-B
GM1 gangliosidosis
Allele origin: germline
Invitae
Accession: SCV000933605.3
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (7)
Comment:
This sequence change replaces arginine with histidine at codon 590 of the GLB1 protein (p.Arg590His). The arginine residue is highly conserved and there is a … (more)

Functional evidence

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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.

Citations for this variant

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Title Author Journal Year Link
MRI/MRS as a surrogate marker for clinical progression in GM1 gangliosidosis. Regier DS American journal of medical genetics. Part A 2016 PMID: 26646981
Prevalence and Novel Mutations of Lysosomal Storage Disorders in United Arab Emirates : LSD in UAE. Al-Jasmi FA JIMD reports 2013 PMID: 23430803
A bicyclic 1-deoxygalactonojirimycin derivative as a novel pharmacological chaperone for GM1 gangliosidosis. Takai T Molecular therapy : the journal of the American Society of Gene Therapy 2013 PMID: 23337983
Chemical chaperone therapy: chaperone effect on mutant enzyme and cellular pathophysiology in β-galactosidase deficiency. Higaki K Human mutation 2011 PMID: 21520340
Expression and characterization of 14 GLB1 mutant alleles found in GM1-gangliosidosis and Morquio B patients. Santamaria R Journal of lipid research 2007 PMID: 17664528
Identification of 14 novel GLB1 mutations, including five deletions, in 19 patients with GM1 gangliosidosis from South America. Santamaria R Clinical genetics 2007 PMID: 17309651
Twenty-one novel mutations in the GLB1 gene identified in a large group of GM1-gangliosidosis and Morquio B patients: possible common origin for the prevalent p.R59H mutation among gypsies. Santamaria R Human mutation 2006 PMID: 16941474
Mutations in acid beta-galactosidase cause GM1-gangliosidosis in American patients. Boustany RM American journal of human genetics 1993 PMID: 8213816
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=GLB1 - - - -

Text-mined citations for rs398123351...

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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 Nov 27, 2021