NM_000642.3(AGL):c.2929C>T (p.Arg977Ter) AND Glycogen storage disease type III

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Jul 15, 2021)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
4 submissions [Details]
Record status:
current
Accession:
RCV000412306.5

Allele description [Variation Report for NM_000642.3(AGL):c.2929C>T (p.Arg977Ter)]

NM_000642.3(AGL):c.2929C>T (p.Arg977Ter)

Gene:
AGL:amylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p21.2
Genomic location:
Preferred name:
NM_000642.3(AGL):c.2929C>T (p.Arg977Ter)
HGVS:
  • NC_000001.11:g.99891336C>T
  • NG_012865.1:g.46253C>T
  • NM_000028.2:c.2929C>T
  • NM_000642.3:c.2929C>TMANE SELECT
  • NM_000643.2:c.2929C>T
  • NM_000644.2:c.2929C>T
  • NM_000646.2:c.2881C>T
  • NP_000019.2:p.Arg977Ter
  • NP_000633.2:p.Arg977Ter
  • NP_000634.2:p.Arg977Ter
  • NP_000635.2:p.Arg977Ter
  • NP_000637.2:p.Arg961Ter
  • NC_000001.10:g.100356892C>T
  • NM_000642.2:c.2929C>T
Protein change:
R961*
Links:
dbSNP: rs531425980
NCBI 1000 Genomes Browser:
rs531425980
Molecular consequence:
  • NM_000028.2:c.2929C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_000642.3:c.2929C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_000643.2:c.2929C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_000644.2:c.2929C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_000646.2:c.2881C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Glycogen storage disease type III (GSD3)
Synonyms:
Glycogen storage disease type 3; Forbes disease; Cori disease; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009291; MedGen: C0017922; Orphanet: 366; OMIM: 232400

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000486438Counsylcriteria provided, single submitter
Likely pathogenic
(Jun 1, 2016)
unknownclinical testing

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

mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf,

Citation Link,

SCV000918399Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Pathogenic
(Sep 22, 2017)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link,

SCV001211777Invitaecriteria provided, single submitter
Pathogenic
(Aug 24, 2020)
germlineclinical testing

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

SCV002055492Nilou-Genome Labcriteria provided, single submitter
Pathogenic
(Jul 15, 2021)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenonot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Elevated serum biotinidase activity in hepatic glycogen storage disorders--a convenient biomarker.

Paesold-Burda P, Baumgartner MR, Santer R, Bosshard NU, Steinmann B.

J Inherit Metab Dis. 2007 Nov;30(6):896-902. Epub 2007 Nov 12.

PubMed [citation]
PMID:
17994282

A mutation analysis of the AGL gene in Korean patients with glycogen storage disease type III.

Ko JS, Moon JS, Seo JK, Yang HR, Chang JY, Park SS.

J Hum Genet. 2014 Jan;59(1):42-5. doi: 10.1038/jhg.2013.117. Epub 2013 Nov 21.

PubMed [citation]
PMID:
24257475
See all PubMed Citations (7)

Details of each submission

From Counsyl, SCV000486438.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000918399.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

Variant summary: The AGL c.2929C>T (p.Arg977X) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g., c.3216_3217delGA [p.Glu1072fsX36] and c.4529dupA [p.Tyr1510X]). MutationTaster predicts a damaging outcome for this variant. This variant was found in 1/30932 control chromosomes at a frequency of 0.0000323, which does not exceed the estimated maximal expected allele frequency of a pathogenic AGL variant (0.0022822). Of note, this is a low-quality site in the gnomAD dataset, which may make interpretation of this data unreliable. The variant has been identified in several compound heterozygote patients diagnosed with GSD III, several of whom were confirmed to have no residual AGL enzyme activity (Paesold-Burda_2007, Lucchiari_2006). One clinical diagnostic laboratory has classified this variant as likely pathogenic. Taken together, this variant is classified as pathogenic.

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

From Invitae, SCV001211777.2

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

Description

This sequence change creates a premature translational stop signal (p.Arg977*) in the AGL gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be in combination with another AGL variant in an individual affected with glycogen storage disease type III (PMID: 16705713). ClinVar contains an entry for this variant (Variation ID: 370992). Loss-of-function variants in AGL are known to be pathogenic (PMID: 19299494). For these reasons, this variant has been classified as Pathogenic.

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

From Nilou-Genome Lab, SCV002055492.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenonot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jan 12, 2022

Support Center