NM_000642.3(AGL):c.1907C>G (p.Ser636Ter) AND Glycogen storage disease type III

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Apr 11, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV002308221.6

Allele description [Variation Report for NM_000642.3(AGL):c.1907C>G (p.Ser636Ter)]

NM_000642.3(AGL):c.1907C>G (p.Ser636Ter)

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.1907C>G (p.Ser636Ter)

HGVS:

NC_000001.11:g.99881083C>G
NG_012865.1:g.36000C>G
NM_000028.3:c.1907C>G
NM_000642.3:c.1907C>GMANE SELECT
NM_000643.3:c.1907C>G
NM_000644.3:c.1907C>G
NM_000646.3:c.1859C>G
NM_001425325.1:c.1907C>G
NM_001425326.1:c.1907C>G
NM_001425327.1:c.1706C>G
NM_001425328.1:c.1703C>G
NM_001425329.1:c.1703C>G
NM_001425332.1:c.1529C>G
NP_000019.2:p.Ser636Ter
NP_000019.2:p.Ser636Ter
NP_000633.2:p.Ser636Ter
NP_000634.2:p.Ser636Ter
NP_000634.2:p.Ser636Ter
NP_000635.2:p.Ser636Ter
NP_000635.2:p.Ser636Ter
NP_000637.2:p.Ser620Ter
NP_000637.2:p.Ser620Ter
NP_001412254.1:p.Ser636Ter
NP_001412255.1:p.Ser636Ter
NP_001412256.1:p.Ser569Ter
NP_001412257.1:p.Ser568Ter
NP_001412258.1:p.Ser568Ter
NP_001412261.1:p.Ser510Ter
NC_000001.10:g.100346639C>G
NM_000028.2:c.1907C>G
NM_000643.2:c.1907C>G
NM_000644.2:c.1907C>G
NM_000646.2:c.1859C>G

Protein change:

S510*

Molecular consequence:

NM_000028.3:c.1907C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_000642.3:c.1907C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_000643.3:c.1907C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_000644.3:c.1907C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_000646.3:c.1859C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001425325.1:c.1907C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001425326.1:c.1907C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001425327.1:c.1706C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001425328.1:c.1703C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001425329.1:c.1703C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001425332.1:c.1529C>G - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002601915	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Women's Health Autosomal Recessive and X-Linked Classification Criteria (2021))	Likely pathogenic (Mar 11, 2022)	unknown	clinical testing	Citation Link,
SCV003503150	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 5, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 19299494, 28492532
SCV004049978	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Apr 11, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002601915

Myriad Genetics, Inc.

criteria provided, single submitter

(Myriad Women's Health Autosomal Recessive and X-Linked Classification Criteria (2021))

Likely pathogenic
(Mar 11, 2022)

unknown

clinical testing

Citation Link,

SCV003503150

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 5, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV004049978

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Apr 11, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Distinct mutations in the glycogen debranching enzyme found in glycogen storage disease type III lead to impairment in diverse cellular functions.

Cheng A, Zhang M, Okubo M, Omichi K, Saltiel AR.

Hum Mol Genet. 2009 Jun 1;18(11):2045-52. doi: 10.1093/hmg/ddp128. Epub 2009 Mar 19.

PubMed [citation]

PMID:: 19299494
PMCID:: PMC2678930

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

See all PubMed Citations (3)

Details of each submission

From Myriad Genetics, Inc., SCV002601915.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

NM_000642.2(AGL):c.1907C>G(S636*) is expected to be pathogenic in the context of glycogen storage disease type III. This variant is predicted to lead to an abnormal or absent protein product due to the creation of a premature termination codon in AGL, a gene where loss-of-function variants are known to be pathogenic. Please note: this variant was assessed in the context of healthy population screening.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003503150.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Ser636*) in the AGL gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in AGL are known to be pathogenic (PMID: 19299494). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1725162). This variant has not been reported in the literature in individuals affected with AGL-related conditions. This variant is not present in population databases (gnomAD no frequency).

#	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

From Genome-Nilou Lab, SCV004049978.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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