NM_000404.4(GLB1):c.1577dup (p.Trp527fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 30, 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:: RCV000798976.4

Allele description [Variation Report for NM_000404.4(GLB1):c.1577dup (p.Trp527fs)]

NM_000404.4(GLB1):c.1577dup (p.Trp527fs)

Gene:

GLB1:galactosidase beta 1 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

3p22.3

Genomic location:

Preferred name:

NM_000404.4(GLB1):c.1577dup (p.Trp527fs)

Other names:

1622_1627insG

HGVS:

NC_000003.12:g.33014218dup
NG_009005.1:g.87990dup
NM_000404.4:c.1577dupMANE SELECT
NM_001079811.3:c.1487dup
NM_001135602.3:c.1184dup
NM_001317040.2:c.1721dup
NM_001393580.1:c.1577dup
NP_000395.3:p.Trp527fs
NP_001073279.2:p.Trp497fs
NP_001129074.2:p.Trp396fs
NP_001303969.2:p.Trp575fs
NP_001380509.1:p.Trp527fs
NC_000003.11:g.33055704_33055705insC
NC_000003.11:g.33055704_33055705insC
NC_000003.11:g.33055710dup
NC_000003.11:g.33055710dupC
NM_000404.2:c.1577dupG
NM_000404.3:c.1577dupG
NM_000404.4:c.1577dupGMANE SELECT

Protein change:

W396fs

Links:

dbSNP: rs794729217

NCBI 1000 Genomes Browser:

rs794729217

Molecular consequence:

NM_000404.4:c.1577dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001079811.3:c.1487dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001135602.3:c.1184dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001317040.2:c.1721dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001393580.1:c.1577dup - frameshift variant - [Sequence Ontology: SO:0001589]

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000938621	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 30, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 18524657, 10338095, 15986423, 16941474, 17309651, 25936995, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000938621

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 30, 2023)

germline

clinical testing

PubMed (7)
[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: review of clinical, molecular, and therapeutic aspects.

Brunetti-Pierri N, Scaglia F.

Mol Genet Metab. 2008 Aug;94(4):391-396. doi: 10.1016/j.ymgme.2008.04.012. Epub 2008 Jun 3. Review.

PubMed [citation]

PMID:: 18524657

Six novel beta-galactosidase gene mutations in Brazilian patients with GM1-gangliosidosis.

Silva CM, Severini MH, Sopelsa A, Coelho JC, Zaha A, d'Azzo A, Giugliani R.

Hum Mutat. 1999;13(5):401-9.

PubMed [citation]

PMID:: 10338095

See all PubMed Citations (7)

Details of each submission

From Invitae, SCV000938621.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This sequence change creates a premature translational stop signal (p.Trp527Leufs*5) in the GLB1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GLB1 are known to be pathogenic (PMID: 18524657). This variant is present in population databases (rs794729217, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with GM1 gangliosidosis (PMID: 10338095, 15986423, 16941474, 17309651, 25936995). This variant is also known as c.1622_1627insG,1606_1611insG, c.1577 1578insG, or c.1572_1577insG. ClinVar contains an entry for this variant (Variation ID: 202191). 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: Apr 15, 2024

ClinVar

Relating variation to medicine