NM_000158.4(GBE1):c.1571G>A (p.Arg524Gln) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 2, 2024
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:: RCV001043400.6

Allele description [Variation Report for NM_000158.4(GBE1):c.1571G>A (p.Arg524Gln)]

NM_000158.4(GBE1):c.1571G>A (p.Arg524Gln)

Gene:

GBE1:1,4-alpha-glucan branching enzyme 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p12.2

Genomic location:

Preferred name:

NM_000158.4(GBE1):c.1571G>A (p.Arg524Gln)

Other names:

NM_000158.4(GBE1):c.1571G>A

HGVS:

NC_000003.12:g.81577972C>T
NG_011810.1:g.188829G>A
NM_000158.4:c.1571G>AMANE SELECT
NP_000149.4:p.Arg524Gln
NC_000003.11:g.81627123C>T
NM_000158.3:c.1571G>A
Q04446:p.Arg524Gln

Protein change:

R524Q; ARG524GLN

Links:

UniProtKB: Q04446#VAR_022434; OMIM: 607839.0007; dbSNP: rs80338673

NCBI 1000 Genomes Browser:

rs80338673

Molecular consequence:

NM_000158.4:c.1571G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Glycogen storage disease, type IV (GSD4)
Synonyms:: GBE1 DEFICIENCY; GLYCOGENOSIS IV; GSD IV; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009292; MedGen: C0017923; Orphanet: 367; OMIM: 232500

Name:: Glycogen storage disease IV, classic hepatic
Synonyms:: GSD IV, CLASSIC HEPATIC
Identifiers:: MedGen: C1856301

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001207144	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 2, 2024)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 10545044, 10762170, 12874416, 15452297, 20479904, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001207144

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 2, 2024)

germline

clinical testing

PubMed (6)
[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

A novel missense mutation in the glycogen branching enzyme gene in a child with myopathy and hepatopathy.

Bruno C, DiRocco M, Lamba LD, Bado M, Marino C, Tsujino S, Shanske S, Stella G, Minetti C, van Diggelen OP, DiMauro S.

Neuromuscul Disord. 1999 Oct;9(6-7):403-7.

PubMed [citation]

PMID:: 10545044

Novel missense mutations in the glycogen-branching enzyme gene in adult polyglucosan body disease.

Ziemssen F, Sindern E, Schröder JM, Shin YS, Zange J, Kilimann MW, Malin JP, Vorgerd M.

Ann Neurol. 2000 Apr;47(4):536-40.

PubMed [citation]

PMID:: 10762170

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001207144.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 524 of the GBE1 protein (p.Arg524Gln). This variant is present in population databases (rs80338673, gnomAD 0.007%). This missense change has been observed in individual(s) with glycogen storage disease IV (PMID: 10545044, 10762170, 12874416, 15452297, 20479904). 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: 2782). 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 GBE1 protein function with a positive predictive value of 95%. 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: Sep 29, 2024

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