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NM_000404.4(GLB1):c.1768C>T (p.Arg590Cys) AND Mucopolysaccharidosis, MPS-IV-B

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 20, 2023
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:
RCV003387787.1

Allele description [Variation Report for NM_000404.4(GLB1):c.1768C>T (p.Arg590Cys)]

NM_000404.4(GLB1):c.1768C>T (p.Arg590Cys)

Gene:
GLB1:galactosidase beta 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3p22.3
Genomic location:
Preferred name:
NM_000404.4(GLB1):c.1768C>T (p.Arg590Cys)
Other names:
p.Arg590Cys
HGVS:
  • NC_000003.12:g.32997311G>A
  • NG_009005.1:g.104892C>T
  • NM_000404.4:c.1768C>TMANE SELECT
  • NM_001079811.3:c.1678C>T
  • NM_001135602.3:c.1375C>T
  • NM_001317040.2:c.1912C>T
  • NM_001393580.1:c.1734+16745C>T
  • NP_000395.3:p.Arg590Cys
  • NP_001073279.2:p.Arg560Cys
  • NP_001129074.2:p.Arg459Cys
  • NP_001303969.2:p.Arg638Cys
  • NC_000003.11:g.33038803G>A
  • NM_000404.2:c.1768C>T
  • NM_000404.3:c.1768C>T
Protein change:
R459C
Links:
dbSNP: rs794727165
NCBI 1000 Genomes Browser:
rs794727165
Molecular consequence:
  • NM_001393580.1:c.1734+16745C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000404.4:c.1768C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001079811.3:c.1678C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001135602.3:c.1375C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001317040.2:c.1912C>T - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
Unknown function

Condition(s)

Name:
Mucopolysaccharidosis, MPS-IV-B (MPS4B)
Synonyms:
MPS IVB; Morquio syndrome B; MPS 4B; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009660; MedGen: C0086652; Orphanet: 582; OMIM: 253010

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004100010Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Pathogenic
(Sep 20, 2023) 		germlineclinical testing

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

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

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, Chabás A, Coll MJ, Miranda CS, Vilageliu L, Grinberg D.

Hum Mutat. 2006 Oct;27(10):1060.

PubMed [citation]
PMID:
16941474

Prevalence and Novel Mutations of Lysosomal Storage Disorders in United Arab Emirates : LSD in UAE.

Al-Jasmi FA, Tawfig N, Berniah A, Ali BR, Taleb M, Hertecant JL, Bastaki F, Souid AK.

JIMD Rep. 2013;10:1-9. doi: 10.1007/8904_2012_182. Epub 2013 Jan 1.

PubMed [citation]
PMID:
23430803
PMCID:
PMC3755583

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004100010.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

Variant summary: GLB1 c.1768C>T (p.Arg590Cys) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 249130 control chromosomes (gnomAD). c.1768C>T has been reported in the literature in multiple individuals affected with GM1 gangliosidosis (example: Al-Jasmi_2012, Santamaria_2007). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity (Santamaria_2007). The following publications have been ascertained in the context of this evaluation (PMID: 23430803, 16941474). Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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

Last Updated: Sep 29, 2024