NM_000404.4(GLB1):c.367G>A (p.Gly123Arg) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 9, 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:: RCV001217770.5

Allele description [Variation Report for NM_000404.4(GLB1):c.367G>A (p.Gly123Arg)]

NM_000404.4(GLB1):c.367G>A (p.Gly123Arg)

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.367G>A (p.Gly123Arg)

HGVS:

NC_000003.12:g.33068849C>T
NG_009005.1:g.33354G>A
NM_000404.4:c.367G>AMANE SELECT
NM_001079811.3:c.277G>A
NM_001135602.3:c.246-3292G>A
NM_001317040.2:c.511G>A
NM_001393580.1:c.367G>A
NP_000395.3:p.Gly123Arg
NP_001073279.2:p.Gly93Arg
NP_001303969.2:p.Gly171Arg
NP_001380509.1:p.Gly123Arg
NC_000003.11:g.33110341C>T

Protein change:

G123R; GLY123ARG

Links:

OMIM: 611458.0006; dbSNP: rs28934274

NCBI 1000 Genomes Browser:

rs28934274

Molecular consequence:

NM_001135602.3:c.246-3292G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000404.4:c.367G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001079811.3:c.277G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001317040.2:c.511G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001393580.1:c.367G>A - missense variant - [Sequence Ontology: SO:0001583]

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

Name:: GM1 gangliosidosis
Synonyms:: Beta galactosidase 1 deficiency; GLB 1 deficiency
Identifiers:: MONDO: MONDO:0018149; MedGen: C0085131

Recent activity

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Mus musculus vomeronasal 1 receptor, C6 (V1rc6), mRNA
Mus musculus vomeronasal 1 receptor, C6 (V1rc6), mRNA
gi|16716554|ref|NM_053236.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001389622	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 9, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 17221873, 22371915, 25936995, 1907800, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001389622

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 9, 2023)

germline

clinical testing

PubMed (5)
[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

GM1 gangliosidosis: molecular analysis of nine patients and development of an RT-PCR assay for GLB1 gene expression profiling.

Caciotti A, Donati MA, Procopio E, Filocamo M, Kleijer W, Wuyts W, Blaumeiser B, d'Azzo A, Simi L, Orlando C, McKenzie F, Fiumara A, Zammarchi E, Morrone A.

Hum Mutat. 2007 Feb;28(2):204.

PubMed [citation]

PMID:: 17221873

A Korean patient with Morquio B disease with a novel c.13_14insA mutation in the GLB1 gene.

Sohn YB, Park HD, Park SW, Kim SH, Cho SY, Ko AR, Ki CS, Yeau S, Jin DK.

Ann Clin Lab Sci. 2012 Winter;42(1):89-93.

PubMed [citation]

PMID:: 22371915

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001389622.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 123 of the GLB1 protein (p.Gly123Arg). This variant is present in population databases (rs28934274, gnomAD 0.003%). This missense change has been observed in individual(s) with GLB1-related conditions (PMID: 1907800, 17221873, 22371915, 25936995). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 928). 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 GLB1 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects GLB1 function (PMID: 1907800). 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 26, 2024

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