NM_000404.4(GLB1):c.1452C>G (p.Asn484Lys) AND multiple conditions

Clinical significance:Likely pathogenic (Last evaluated: Jul 31, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001379670.1

Allele description [Variation Report for NM_000404.4(GLB1):c.1452C>G (p.Asn484Lys)]

NM_000404.4(GLB1):c.1452C>G (p.Asn484Lys)

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.1452C>G (p.Asn484Lys)
HGVS:
  • NC_000003.12:g.33016736G>C
  • NG_009005.1:g.85467C>G
  • NM_000404.4:c.1452C>GMANE SELECT
  • NM_001079811.3:c.1362C>G
  • NM_001135602.3:c.1059C>G
  • NM_001317040.2:c.1596C>G
  • NM_001393580.1:c.1452C>G
  • NP_000395.3:p.Asn484Lys
  • NP_001073279.2:p.Asn454Lys
  • NP_001129074.2:p.Asn353Lys
  • NP_001303969.2:p.Asn532Lys
  • NP_001380509.1:p.Asn484Lys
  • NC_000003.11:g.33058228G>C
  • NM_000404.2:c.1452C>G
Protein change:
N353K
Links:
dbSNP: rs968221254
NCBI 1000 Genomes Browser:
rs968221254
Molecular consequence:
  • NM_000404.4:c.1452C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001079811.3:c.1362C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001135602.3:c.1059C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001317040.2:c.1596C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001393580.1:c.1452C>G - 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
SCV001577510Invitaecriteria provided, single submitter
Likely pathogenic
(Jul 31, 2020)
germlineclinical testing

PubMed (2)
[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

Novel mutations (Asn 484 Lys, Thr 500 Ala, Gly 438 Glu) in Morquio B disease.

Bagshaw RD, Zhang S, Hinek A, Skomorowski MA, Whelan D, Clarke JT, Callahan JW.

Biochim Biophys Acta. 2002 Dec 12;1588(3):247-53.

PubMed [citation]
PMID:
12393180

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV001577510.1

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

Description

This sequence change replaces asparagine with lysine at codon 484 of the GLB1 protein (p.Asn484Lys). The asparagine residue is highly conserved and there is a moderate physicochemical difference between asparagine and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with mucopolysaccharidosis, type IVB (PMID: 12393180). ClinVar contains an entry for this variant (Variation ID: 553506). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Nov 27, 2021

Support Center