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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004100010	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Sep 20, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 16941474, 23430803 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004100010

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Sep 20, 2023)

germline

clinical testing

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

Citation Link

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

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

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical 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.

#	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: Sep 29, 2024

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