NM_000158.4(GBE1):c.1909C>T (p.Arg637Ter) AND GBE1-related disorder

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Apr 28, 2017
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:: RCV000303766.5

Allele description [Variation Report for NM_000158.4(GBE1):c.1909C>T (p.Arg637Ter)]

NM_000158.4(GBE1):c.1909C>T (p.Arg637Ter)

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.1909C>T (p.Arg637Ter)

Other names:

NM_000158.4(GBE1):c.1909C>T; p.Arg637Ter

HGVS:

NC_000003.12:g.81535220G>A
NG_011810.1:g.231581C>T
NM_000158.4:c.1909C>TMANE SELECT
NP_000149.4:p.Arg637Ter
NC_000003.11:g.81584371G>A
NM_000158.3:c.1909C>T

Protein change:

R637*

Links:

dbSNP: rs766935302

NCBI 1000 Genomes Browser:

rs766935302

Molecular consequence:

NM_000158.4:c.1909C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: GBE1-related disorder
Synonyms:: GBE1-Related Disorders; GBE1-related condition
Identifiers:: MedGen: CN239402

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000446284	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 09 May 2019)	Likely pathogenic (Apr 28, 2017)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 19438752, 15452297, 15520786 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000446284

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 09 May 2019)

Likely pathogenic
(Apr 28, 2017)

germline

clinical testing

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

Citation Link

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

Glycogen branching enzyme deficiency in an infant with severe congenital hypotonia: an emerging diagnosis of muscle weakness in the perinatal period.

Jimenez-Mallebrera C, Nascimento A, Cusi V, Corbera JR, Rolland MO, Froissart R, Olivé M, Ferrer I, Colomer J.

Histopathology. 2009 May;54(6):765-8. doi: 10.1111/j.1365-2559.2009.03281.x. No abstract available.

PubMed [citation]

PMID:: 19438752

Clinical and genetic heterogeneity of branching enzyme deficiency (glycogenosis type IV).

Bruno C, van Diggelen OP, Cassandrini D, Gimpelev M, Giuffrè B, Donati MA, Introvini P, Alegria A, Assereto S, Morandi L, Mora M, Tonoli E, Mascelli S, Traverso M, Pasquini E, Bado M, Vilarinho L, van Noort G, Mosca F, DiMauro S, Zara F, Minetti C.

Neurology. 2004 Sep 28;63(6):1053-8.

PubMed [citation]

PMID:: 15452297

See all PubMed Citations (3)

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000446284.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The GBE1 c.1909C>T (p.Arg637Ter) variant is a stop-gained variant that has been reported in three studies, in which it is found in a total of three individuals with the most severe form of glycogen storage disorder type IV, including in one in a homozygous state and in two in a compound heterozygous state (Bruno et al. 2004; Janecke et al. 2004; Jimenez-Mallebrera et al. 2009). The p.Arg637Ter variant was absent from 120 control chromosomes but reported at a frequency of 0.00005 in the European (non-Finnish) population of the Exome Aggregation Consortium. Functional studies in both individual fibroblasts and muscle tissue demonstrated that the variant resulted in less than five percent of glycogen branching enzyme activity compared to wild type (Bruno et al. 2004; Jimenez-Mallebrera et al. 2009). Due to the potential impact of stop-gained variants and the supporting evidence, the p.Arg637Ter variant is considered to be pathogenic for GBE1-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

#	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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