NM_000642.3(AGL):c.325G>T (p.Val109Leu) AND Glycogen storage disease type III

Germline classification:: Uncertain significance (4 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:: RCV001248480.8

Allele description [Variation Report for NM_000642.3(AGL):c.325G>T (p.Val109Leu)]

NM_000642.3(AGL):c.325G>T (p.Val109Leu)

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.325G>T (p.Val109Leu)

HGVS:

NC_000001.11:g.99862288G>T
NG_012865.1:g.17205G>T
NM_000028.3:c.325G>T
NM_000642.3:c.325G>TMANE SELECT
NM_000643.3:c.325G>T
NM_000644.3:c.325G>T
NM_000646.3:c.277G>T
NM_001425325.1:c.325G>T
NM_001425326.1:c.325G>T
NM_001425327.1:c.325G>T
NM_001425328.1:c.325G>T
NM_001425329.1:c.325G>T
NP_000019.2:p.Val109Leu
NP_000019.2:p.Val109Leu
NP_000633.2:p.Val109Leu
NP_000634.2:p.Val109Leu
NP_000634.2:p.Val109Leu
NP_000635.2:p.Val109Leu
NP_000635.2:p.Val109Leu
NP_000637.2:p.Val93Leu
NP_000637.2:p.Val93Leu
NP_001412254.1:p.Val109Leu
NP_001412255.1:p.Val109Leu
NP_001412256.1:p.Val109Leu
NP_001412257.1:p.Val109Leu
NP_001412258.1:p.Val109Leu
NC_000001.10:g.100327844G>T
NC_000001.10:g.100327844G>T
NM_000028.2:c.325G>T
NM_000642.2:c.325G>T
NM_000643.2:c.325G>T
NM_000644.2:c.325G>T
NM_000646.2:c.277G>T

Protein change:

V109L

Links:

dbSNP: rs369068676

NCBI 1000 Genomes Browser:

rs369068676

Molecular consequence:

NM_000028.3:c.325G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_000642.3:c.325G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_000643.3:c.325G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_000644.3:c.325G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_000646.3:c.277G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001425325.1:c.325G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001425326.1:c.325G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001425327.1:c.325G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001425328.1:c.325G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001425329.1:c.325G>T - missense variant - [Sequence Ontology: SO:0001583]

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

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Glycos_transf_1, partial [uncultured Candidatus Desulforudis sp.]
Glycos_transf_1, partial [uncultured Candidatus Desulforudis sp.]
gi|643017809|gb|AIA85489.1|

Protein
CAZy families GT2 protein, partial [uncultured Candidatus Desulforudis sp.]
CAZy families GT2 protein, partial [uncultured Candidatus Desulforudis sp.]
gi|643035154|gb|AIA94201.1|

Protein
CAZy families GT51 protein, partial [uncultured Candidatus Desulforudis sp.]
CAZy families GT51 protein, partial [uncultured Candidatus Desulforudis sp.]
gi|643024905|gb|AIA89052.1|

Protein
uncharacterized protein C2orf92 isoform X7 [Homo sapiens]
uncharacterized protein C2orf92 isoform X7 [Homo sapiens]
gi|2462496681|ref|XP_054188970.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001421968	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 24, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31508908, 28492532
SCV002091440	Natera, Inc.	no assertion criteria provided	Uncertain significance (Jan 10, 2020)	germline	clinical testing
SCV002793581	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Dec 13, 2021)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004049918	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (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

Glycogen storage diseases: Twenty-seven new variants in a cohort of 125 patients.

Sperb-Ludwig F, Pinheiro FC, Bettio Soares M, Nalin T, Ribeiro EM, Steiner CE, Ribeiro Valadares E, Porta G, Fishinger Moura de Souza C, Schwartz IVD.

Mol Genet Genomic Med. 2019 Nov;7(11):e877. doi: 10.1002/mgg3.877. Epub 2019 Sep 11.

PubMed [citation]

PMID:: 31508908
PMCID:: PMC6825860

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001421968.3

#	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 replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 109 of the AGL protein (p.Val109Leu). This variant is present in population databases (rs369068676, gnomAD 0.09%). This missense change has been observed in individual(s) with clinical features of AGL-related conditions (PMID: 31508908). ClinVar contains an entry for this variant (Variation ID: 972445). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt AGL protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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 Natera, Inc., SCV002091440.1

#	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 Fulgent Genetics, Fulgent Genetics, SCV002793581.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genome-Nilou Lab, SCV004049918.1

#	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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