NM_000642.3(AGL):c.1172A>G (p.Tyr391Cys) AND Glycogen storage disease type III

Germline classification:: Uncertain significance (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:: RCV001241206.7

Allele description [Variation Report for NM_000642.3(AGL):c.1172A>G (p.Tyr391Cys)]

NM_000642.3(AGL):c.1172A>G (p.Tyr391Cys)

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.1172A>G (p.Tyr391Cys)

HGVS:

NC_000001.11:g.99875243A>G
NG_012865.1:g.30160A>G
NM_000028.3:c.1172A>G
NM_000642.3:c.1172A>GMANE SELECT
NM_000643.3:c.1172A>G
NM_000644.3:c.1172A>G
NM_000646.3:c.1124A>G
NM_001425325.1:c.1172A>G
NM_001425326.1:c.1172A>G
NM_001425328.1:c.968A>G
NM_001425329.1:c.968A>G
NM_001425332.1:c.794A>G
NP_000019.2:p.Tyr391Cys
NP_000019.2:p.Tyr391Cys
NP_000633.2:p.Tyr391Cys
NP_000634.2:p.Tyr391Cys
NP_000634.2:p.Tyr391Cys
NP_000635.2:p.Tyr391Cys
NP_000635.2:p.Tyr391Cys
NP_000637.2:p.Tyr375Cys
NP_000637.2:p.Tyr375Cys
NP_001412254.1:p.Tyr391Cys
NP_001412255.1:p.Tyr391Cys
NP_001412257.1:p.Tyr323Cys
NP_001412258.1:p.Tyr323Cys
NP_001412261.1:p.Tyr265Cys
NC_000001.10:g.100340799A>G
NM_000028.2:c.1172A>G
NM_000642.2:c.1172A>G
NM_000643.2:c.1172A>G
NM_000644.2:c.1172A>G
NM_000646.2:c.1124A>G

Protein change:

Y265C

Links:

dbSNP: rs775949246

NCBI 1000 Genomes Browser:

rs775949246

Molecular consequence:

NM_000028.3:c.1172A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_000642.3:c.1172A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_000643.3:c.1172A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_000644.3:c.1172A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_000646.3:c.1124A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001425325.1:c.1172A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001425326.1:c.1172A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001425328.1:c.968A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001425329.1:c.968A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001425332.1:c.794A>G - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001414210	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 24, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002091478	Natera, Inc.	no assertion criteria provided	Uncertain significance (Sep 12, 2020)	germline	clinical testing
SCV004049954	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]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001414210

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 24, 2022)

germline

clinical testing

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

SCV002091478

Natera, Inc.

no assertion criteria provided

Uncertain significance
(Sep 12, 2020)

germline

clinical testing

SCV004049954

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

Citations

PubMed

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001414210.3

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

Description

This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 391 of the AGL protein (p.Tyr391Cys). This variant is present in population databases (rs775949246, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with AGL-related conditions. ClinVar contains an entry for this variant (Variation ID: 966513). 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 not 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., SCV002091478.1

#	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 Genome-Nilou Lab, SCV004049954.1

#	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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