U.S. flag

An official website of the United States government

NM_000404.4(GLB1):c.335A>C (p.His112Pro) 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:
RCV002531261.3

Allele description [Variation Report for NM_000404.4(GLB1):c.335A>C (p.His112Pro)]

NM_000404.4(GLB1):c.335A>C (p.His112Pro)

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.335A>C (p.His112Pro)
HGVS:
  • NC_000003.12:g.33068881T>G
  • NG_009005.1:g.33322A>C
  • NM_000404.4:c.335A>CMANE SELECT
  • NM_001079811.3:c.245A>C
  • NM_001135602.3:c.246-3324A>C
  • NM_001317040.2:c.479A>C
  • NM_001393580.1:c.335A>C
  • NP_000395.3:p.His112Pro
  • NP_001073279.2:p.His82Pro
  • NP_001303969.2:p.His160Pro
  • NP_001380509.1:p.His112Pro
  • NC_000003.11:g.33110373T>G
  • NM_000404.2:c.335A>C
Protein change:
H112P
Links:
dbSNP: rs753965226
NCBI 1000 Genomes Browser:
rs753965226
Molecular consequence:
  • NM_001135602.3:c.246-3324A>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000404.4:c.335A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001079811.3:c.245A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001317040.2:c.479A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001393580.1:c.335A>C - 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

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV003525100Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Dec 9, 2023)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Abnormal DaTscan in GM1-Gangliosidosis Type III Manifesting with Dystonia-Parkinsonism.

Koya Kutty S, Magrinelli F, Milner AV, Bhatia KP.

Mov Disord Clin Pract. 2022 Aug;9(6):825-828. doi: 10.1002/mdc3.13512. No abstract available.

PubMed [citation]
PMID:
35937492
PMCID:
PMC9346251

Phenotype determining alleles in GM1 gangliosidosis patients bearing novel GLB1 mutations.

Hofer D, Paul K, Fantur K, Beck M, Roubergue A, Vellodi A, Poorthuis BJ, Michelakakis H, Plecko B, Paschke E.

Clin Genet. 2010 Sep;78(3):236-46. doi: 10.1111/j.1399-0004.2010.01379.x. Epub 2010 Feb 11.

PubMed [citation]
PMID:
20175788
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003525100.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces histidine, which is basic and polar, with proline, which is neutral and non-polar, at codon 112 of the GLB1 protein (p.His112Pro). This variant is present in population databases (rs753965226, gnomAD 0.004%). This missense change has been observed in individual(s) with GM1-gangliosidosis (PMID: 20175788, 35937492). 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: 555030). 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: 20175788). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Sep 29, 2024