NM_000642.3(AGL):c.4529dup (p.Tyr1510Ter) AND Glycogen storage disease IIIa

Clinical significance:Pathogenic (Last evaluated: Jan 6, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:

Allele description [Variation Report for NM_000642.3(AGL):c.4529dup (p.Tyr1510Ter)]

NM_000642.3(AGL):c.4529dup (p.Tyr1510Ter)

AGL:amylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase [Gene - OMIM - HGNC]
Variant type:
Cytogenetic location:
Genomic location:
Preferred name:
NM_000642.3(AGL):c.4529dup (p.Tyr1510Ter)
  • NC_000001.11:g.99921581dup
  • NG_012865.1:g.76498dup
  • NM_000028.2:c.4529dup
  • NM_000642.3:c.4529dupMANE SELECT
  • NM_000643.2:c.4529dup
  • NM_000644.2:c.4529dup
  • NM_000646.2:c.4481dup
  • NP_000019.2:p.Tyr1510Ter
  • NP_000633.2:p.Tyr1510Ter
  • NP_000634.2:p.Tyr1510Ter
  • NP_000635.2:p.Tyr1510Ter
  • NP_000637.2:p.Tyr1494Ter
  • NC_000001.10:g.100387137dup
  • NM_000642.2:c.4529dupA
  • NM_000642.3:c.4529dupAMANE SELECT
  • NP_000633.2:p.Tyr1510*
Protein change:
OMIM: 610860.0001; dbSNP: rs387906244
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000028.2:c.4529dup - nonsense - [Sequence Ontology: SO:0001587]
  • NM_000642.3:c.4529dup - nonsense - [Sequence Ontology: SO:0001587]
  • NM_000643.2:c.4529dup - nonsense - [Sequence Ontology: SO:0001587]
  • NM_000644.2:c.4529dup - nonsense - [Sequence Ontology: SO:0001587]
  • NM_000646.2:c.4481dup - nonsense - [Sequence Ontology: SO:0001587]


Glycogen storage disease IIIa (GSD IIIa)
MedGen: C1968739

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000021302OMIMno assertion criteria providedPathogenic
(Jan 1, 1997)
germlineliterature only

PubMed (1)
[See all records that cite this PMID]

Yang, B.-Z., Ding, J.-H., Bao, Y., Eason, J. F. M., Chen, Y.-T. Molecular basis of the enzymatic variability in type III glycogen storage disease (GSD-III). (Abstract) Am. J. Hum. Genet. 51 (suppl.): A28, 1992.,

SCV000697534Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
(Jan 6, 2017)
germlineclinical testing

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

LabCorp Variant Classification Summary - May 2015.docx

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing


Details of each submission

From OMIM, SCV000021302.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)


In a child with an unusually severe phenotype of glycogen storage disease type IIIa (GSD3A; 232400) manifested in both liver and muscle, Shen et al. (1997) identified a homozygous 1-bp insertion (4529insA) in the 3-prime coding region of the AGL gene. The mutation created a termination codon at residue 1510 of their sequence. (They stated that amino acid residue 1510 in their study corresponded to residue 1493 of the Yang et al. (1992) sequence.) The child had recurrent hypoglycemia, seizures, severe cardiomegaly, and hepatomegaly, and died at 4 years of age.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000697534.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)


Variant summary: The AGL c.4529dupA (p.Tyr1510X) variant results in a premature termination codon, predicted to cause a truncated or absent AGL protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 2/121034 (1/60517), which does not exceed the estimated maximal expected allele frequency for a pathogenic AGL variant of 1/438. Multiple publications have cited the variant in affected individuals, who were homozygous and compound heterozygous. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely pathogenic/pathogenic. Taken together, this variant is classified as pathogenic.

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

Last Updated: Nov 27, 2021

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