Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation

ClinVar Genomic variation as it relates to human health

Advanced search

NM_000404.4(GLB1):c.442C>A (p.Arg148Ser)

Help
Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
6 (Most recent: Sep 15, 2021)
Last evaluated:
Aug 2, 2021
Accession:
VCV000551757.8
Variation ID:
551757
Description:
single nucleotide variant
Help

NM_000404.4(GLB1):c.442C>A (p.Arg148Ser)

Allele ID
543207
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
3p22.3
Genomic location
3: 33068245 (GRCh38) GRCh38 UCSC
3: 33109737 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000003.11:g.33109737G>T
NC_000003.12:g.33068245G>T
NG_009005.1:g.33958C>A
... more HGVS
Protein change
R148S, R118S, R196S
Other names
-
Canonical SPDI
NC_000003.12:33068244:G:T
Functional consequence
-
Global minor allele frequency (GMAF)
0.00020 (T)

Allele frequency
1000 Genomes Project 0.00020
Trans-Omics for Precision Medicine (TOPMed) 0.00008
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00025
Links
dbSNP: rs192732174
VarSome
Help

Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 2 criteria provided, multiple submitters, no conflicts Aug 2, 2021 RCV000727559.3
Likely pathogenic 1 criteria provided, single submitter May 15, 2017 RCV000666897.1
Pathogenic 1 criteria provided, single submitter May 11, 2018 RCV000780304.1
Pathogenic 1 criteria provided, single submitter Oct 1, 2020 RCV001055679.2
not provided 1 no assertion provided - RCV001175301.1

Clinical features observed in individuals with this variant

Help
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

Help
Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(May 15, 2017)
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: SCV000791267.1
Submitted: (Jul 10, 2018)
Evidence details
Publications
PubMed (4)
Pathogenic
(Jan 17, 2018)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000854793.1
Submitted: (Sep 19, 2018)
Evidence details
Publications
PubMed (2)
Other databases
http://www.egl-eurofins.com/emvc…
Pathogenic
(May 11, 2018)
criteria provided, single submitter
Method: clinical testing
Mucopolysaccharidosis, MPS-IV-B
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000917466.1
Submitted: (Apr 24, 2019)
Evidence details
Publications
PubMed (6)
Comment:
Variant summary: GLB1 c.442C>A (p.Arg148Ser) results in a non-conservative amino acid change located in the Glycoside hydrolase 35 catalytic domain of the encoded protein sequence. … (more)
Pathogenic
(Oct 01, 2020)
criteria provided, single submitter
Method: clinical testing
Mucopolysaccharidosis, MPS-IV-B
GM1 gangliosidosis
Allele origin: germline
Invitae
Accession: SCV001220079.2
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (7)
Comment:
This sequence change replaces arginine with serine at codon 148 of the GLB1 protein (p.Arg148Ser). The arginine residue is highly conserved and there is a … (more)
Pathogenic
(Aug 02, 2021)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV001871370.1
Submitted: (Sep 15, 2021)
Evidence details
Comment:
Published functional studies demonstrate R148S leads to a decrease in enzymatic activity (Zhang et al., 2000); Not observed at significant frequency in large population cohorts … (more)
not provided
(-)
no assertion provided
Method: phenotyping only
GM1 gangliosidosis
Allele origin: unknown
GenomeConnect - GM1
Accession: SCV001338923.1
Submitted: (Apr 22, 2020)
Evidence details
Comment:
Variant interpreted as Pathogenic and reported on 09-25-2014 by Lab or GTR ID 239772. GenomeConnect-GM1 assertions are reported exactly as they appear on the patient-provided … (more)

Functional evidence

Help
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

Help
Title Author Journal Year Link
Distinct progression patterns of brain disease in infantile and juvenile gangliosidoses: Volumetric quantitative MRI study. Nestrasil I Molecular genetics and metabolism 2018 PMID: 29352662
Recurrent and novel GLB1 mutations in India. Bidchol AM Gene 2015 PMID: 25936995
Biochemical and molecular characterization of novel mutations in GLB1 and NEU1 in patient cells with lysosomal storage disorders. Kwak JE Biochemical and biophysical research communications 2015 PMID: 25600812
Beta-galactosidase deficiencies and novel GLB1 mutations in three Chinese patients with Morquio B disease or GM1 gangliosidosis. Lei HL World journal of pediatrics : WJP 2012 PMID: 23151865
Phenotype determining alleles in GM1 gangliosidosis patients bearing novel GLB1 mutations. Hofer D Clinical genetics 2010 PMID: 20175788
GM1 gangliosidosis: molecular analysis of nine patients and development of an RT-PCR assay for GLB1 gene expression profiling. Caciotti A Human mutation 2007 PMID: 17221873
Dystonia and parkinsonism in GM1 type 3 gangliosidosis. Roze E Movement disorders : official journal of the Movement Disorder Society 2005 PMID: 15986423
Four novel mutations in patients from the Middle East with the infantile form of GM1-gangliosidosis. Georgiou T Human mutation 2004 PMID: 15365997
Impaired elastic-fiber assembly by fibroblasts from patients with either Morquio B disease or infantile GM1-gangliosidosis is linked to deficiency in the 67-kD spliced variant of beta-galactosidase. Hinek A American journal of human genetics 2000 PMID: 10841810
Characterization of beta-galactosidase mutations Asp332-->Asn and Arg148-->Ser, and a polymorphism, Ser532-->Gly, in a case of GM1 gangliosidosis. Zhang S The Biochemical journal 2000 PMID: 10839995
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=GLB1 - - - -

Text-mined citations for rs192732174...

Help
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