NM_000152.5(GAA):c.1315A>G (p.Met439Val) AND Glycogen storage disease, type II

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 28, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV003052669.2

Allele description [Variation Report for NM_000152.5(GAA):c.1315A>G (p.Met439Val)]

NM_000152.5(GAA):c.1315A>G (p.Met439Val)

Gene:

GAA:alpha glucosidase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q25.3

Genomic location:

Preferred name:

NM_000152.5(GAA):c.1315A>G (p.Met439Val)

HGVS:

NC_000017.11:g.80108817A>G
NG_009822.1:g.12262A>G
NM_000152.5:c.1315A>GMANE SELECT
NM_001079803.3:c.1315A>G
NM_001079804.3:c.1315A>G
NM_001406741.1:c.1315A>G
NM_001406742.1:c.1315A>G
NP_000143.2:p.Met439Val
NP_000143.2:p.Met439Val
NP_001073271.1:p.Met439Val
NP_001073272.1:p.Met439Val
NP_001393670.1:p.Met439Val
NP_001393671.1:p.Met439Val
LRG_673t1:c.1315A>G
LRG_673:g.12262A>G
LRG_673p1:p.Met439Val
NC_000017.10:g.78082616A>G
NM_000152.3:c.1315A>G

Protein change:

M439V

Molecular consequence:

NM_000152.5:c.1315A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001079803.3:c.1315A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001079804.3:c.1315A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406741.1:c.1315A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406742.1:c.1315A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Glycogen storage disease, type II (GSD2)
Synonyms:: ACID ALPHA-GLUCOSIDASE DEFICIENCY; GLYCOGENOSIS, GENERALIZED, CARDIAC FORM; GSD II; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009290; MedGen: C0017921; Orphanet: 365; OMIM: 232300

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003445685	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 28, 2022)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 17092519, 20202878, 23884227, 25213570, 29124014, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003445685

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 28, 2022)

germline

clinical testing

PubMed (6)
[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	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Two new missense mutations of GAA in late onset glycogen storage disease type II.

Park YE, Park KH, Lee CH, Kim CM, Kim DS.

J Neurol Sci. 2006 Dec 21;251(1-2):113-7. Epub 2006 Nov 7.

PubMed [citation]

PMID:: 17092519

Prognostic factors for the late onset Pompe disease with enzyme replacement therapy: from our experience of 4 cases including an autopsy case.

Kobayashi H, Shimada Y, Ikegami M, Kawai T, Sakurai K, Urashima T, Ijima M, Fujiwara M, Kaneshiro E, Ohashi T, Eto Y, Ishigaki K, Osawa M, Kyosen SO, Ida H.

Mol Genet Metab. 2010 May;100(1):14-9. doi: 10.1016/j.ymgme.2010.01.015. Epub 2010 Feb 4.

PubMed [citation]

PMID:: 20202878

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003445685.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 439 of the GAA protein (p.Met439Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GAA-related conditions. 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 GAA protein function. This variant disrupts the p.Met439 amino acid residue in GAA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17092519, 20202878, 23884227, 25213570, 29124014). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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

Last Updated: Sep 29, 2024

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