NM_000642.2(AGL):c.3965delT (p.Val1322Alafs) AND Glycogen storage disease type III

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Nov 14, 2017
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:: RCV000020378.2

Allele description

NM_000642.2(AGL):c.3965delT (p.Val1322Alafs)

Gene:

AGL:amylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

1p21.2

Genomic location:

Preferred name:

NM_000642.2(AGL):c.3965delT (p.Val1322Alafs)

HGVS:

NC_000001.11:g.99913542delT
NG_012865.1:g.68459delT
NM_000642.2:c.3965delT
NP_000633.2:p.Val1322Alafs
NC_000001.10:g.100379098delT

Links:

OMIM: 610860.0010; dbSNP: rs113994132

NCBI 1000 Genomes Browser:

rs113994132

Allele Frequency:

0.00001(-)

Molecular consequence:

NM_000642.2:c.3965delT - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Glycogen storage disease type III (GSD3)
Identifiers:: MedGen: C0017922; Orphanet: 366; OMIM: 232400

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000040766	GeneReviews	no assertion criteria provided	pathologic (Sep 6, 2012)	not provided	curation
SCV000229304	EGL Genetic Diagnostics,Eurofins Clinical Diagnostics	criteria provided, single submitter (EGL Classification Definitions)	Pathogenic (Jun 13, 2014)	germline	clinical testing	Citation Link,
SCV000752138	Invitae,	criteria provided, single submitter (Nykamp K et al. (Genet Med 2017))	Pathogenic (Nov 14, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 10655153, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000040766

GeneReviews

no assertion criteria provided

pathologic
(Sep 6, 2012)

not provided

curation

SCV000229304

EGL Genetic Diagnostics,Eurofins Clinical Diagnostics

criteria provided, single submitter

(EGL Classification Definitions)

Pathogenic
(Jun 13, 2014)

germline

clinical testing

Citation Link,

SCV000752138

Invitae,

criteria provided, single submitter

(Nykamp K et al. (Genet Med 2017))

Pathogenic
(Nov 14, 2017)

germline

clinical testing

PubMed (2)
[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	not provided	not provided	not provided	not provided	not provided	not provided	not provided	curation
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Genotype-phenotype correlation in two frequent mutations and mutation update in type III glycogen storage disease.

Shaiu WL, Kishnani PS, Shen J, Liu HM, Chen YT.

Mol Genet Metab. 2000 Jan;69(1):16-23.

PubMed [citation]

PMID:: 10655153

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From GeneReviews, SCV000040766.1

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

Description

Converted during submission to Pathogenic.

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

From EGL Genetic Diagnostics,Eurofins Clinical Diagnostics, SCV000229304.4

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

#	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 Invitae,, SCV000752138.1

#	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.Val1322Alafs*27) in the AGL gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs113994132, ExAC 0.002%). This variant has been reported as homozygous in an individual affected with glycogen storage disease type III (PMID: 10655153). ClinVar contains an entry for this variant (Variation ID: 1103). Loss-of-function variants in AGL are known to be pathogenic (PMID: 19299494). For these reasons, this variant has been classified as 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: Nov 26, 2018

ClinVar

Relating variation to medicine