NC_000003.12:g.(?_81490387)_(81705633_?)del AND multiple conditions

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Dec 31, 2018
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:: RCV000708305.3

Allele description [Variation Report for NC_000003.12:g.(?_81490387)_(81705633_?)del]

NC_000003.12:g.(?_81490387)_(81705633_?)del

Genes:

LOC129937076:ATAC-STARR-seq lymphoblastoid silent region 14538 [Gene]
GBE1:1,4-alpha-glucan branching enzyme 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

3p12.2

Genomic location:

Preferred name:

NC_000003.12:g.(?_81490387)_(81705633_?)del

HGVS:

NC_000003.12:g.(?_81490387)_(81705633_?)del
NC_000003.11:g.(?_81539538)_(81754784_?)del

Condition(s)

Name:: Glycogen storage disease, type IV (GSD4)
Synonyms:: AMYLOPECTINOSIS; ANDERSEN DISEASE; BRANCHER DEFICIENCY; 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
SCV000837415	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Dec 31, 2018)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 25665141, 26385640, 23034915, 26199317, 8613547, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000837415

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Dec 31, 2018)

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

Deep intronic GBE1 mutation in manifesting heterozygous patients with adult polyglucosan body disease.

Akman HO, Kakhlon O, Coku J, Peverelli L, Rosenmann H, Rozenstein-Tsalkovich L, Turnbull J, Meiner V, Chama L, Lerer I, Shpitzen S, Leitersdorf E, Paradas C, Wallace M, Schiffmann R, DiMauro S, Lossos A, Minassian BA.

JAMA Neurol. 2015 Apr;72(4):441-5. doi: 10.1001/jamaneurol.2014.4496. Erratum in: JAMA Neurol. 2015 Apr;72(4):481. doi: 10.1001/jamaneurol.2015.0365..

PubMed [citation]

PMID:: 25665141

A novel mouse model that recapitulates adult-onset glycogenosis type 4.

Orhan Akman H, Emmanuele V, Kurt YG, Kurt B, Sheiko T, DiMauro S, Craigen WJ.

Hum Mol Genet. 2015 Dec 1;24(23):6801-10. doi: 10.1093/hmg/ddv385. Epub 2015 Sep 18.

PubMed [citation]

PMID:: 26385640
PMCID:: PMC4634380

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000837415.2

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

Description

This variant is a gross deletion of the genomic region encompassing exons 2-16 of the GBE1 gene. The 5' boundary is likely confined to intron 1. The 3' end of this event is unknown as it extends through the termination codon beyond the assayed region for this gene and may encompass additional genes. While this deletion is not anticipated to result in nonsense mediated decay, it is expected to create a truncated protein product or disrupt mRNA translation. This variant has not been reported in the literature in individuals with GBE1-related disease. Two missense substitutions (p.Tyr329Cys and p.Tyr329Ser) have been determined to be pathogenic (PMID: 23034915, 8613547, 25665141, 26199317, 26385640). This suggests that the tyrosine residue is critical for GBE1 protein function and that deletion of this region may also be pathogenic. 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.

#	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: May 16, 2025

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