NM_000152.5(GAA):c.1309C>A (p.Arg437Ser) AND Glycogen storage disease, type II

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Sep 20, 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:: RCV003083785.3

Allele description [Variation Report for NM_000152.5(GAA):c.1309C>A (p.Arg437Ser)]

NM_000152.5(GAA):c.1309C>A (p.Arg437Ser)

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.1309C>A (p.Arg437Ser)

HGVS:

NC_000017.11:g.80108811C>A
NG_009822.1:g.12256C>A
NM_000152.5:c.1309C>AMANE SELECT
NM_001079803.3:c.1309C>A
NM_001079804.3:c.1309C>A
NM_001406741.1:c.1309C>A
NM_001406742.1:c.1309C>A
NP_000143.2:p.Arg437Ser
NP_000143.2:p.Arg437Ser
NP_001073271.1:p.Arg437Ser
NP_001073272.1:p.Arg437Ser
NP_001393670.1:p.Arg437Ser
NP_001393671.1:p.Arg437Ser
LRG_673t1:c.1309C>A
LRG_673:g.12256C>A
LRG_673p1:p.Arg437Ser
NC_000017.10:g.78082610C>A
NM_000152.3:c.1309C>A

Protein change:

R437S

Molecular consequence:

NM_000152.5:c.1309C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001079803.3:c.1309C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001079804.3:c.1309C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406741.1:c.1309C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406742.1:c.1309C>A - 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
SCV003466353	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Sep 20, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 12601120, 17805474, 29124014, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003466353

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Sep 20, 2022)

germline

clinical testing

PubMed (4)
[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

Juvenile-onset glycogen storage disease type II with novel mutations in acid alpha-glucosidase gene.

Lam CW, Yuen YP, Chan KY, Tong SF, Lai CK, Chow TC, Lee KC, Chan YW, Martiniuk F.

Neurology. 2003 Feb 25;60(4):715-7.

PubMed [citation]

PMID:: 12601120

Structural and biochemical studies on Pompe disease and a "pseudodeficiency of acid alpha-glucosidase".

Tajima Y, Matsuzawa F, Aikawa SI, Okumiya T, Yoshimizu M, Tsukimura T, Ikekita M, Tsujino S, Tsuji A, Edmunds T, Sakuraba H.

J Hum Genet. 2007;52(11):898-906. doi: 10.1007/s10038-007-0191-9. Epub 2007 Sep 6.

PubMed [citation]

PMID:: 17805474

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003466353.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Arg437 amino acid residue in GAA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12601120, 17805474, 29124014). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with GAA-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 437 of the GAA protein (p.Arg437Ser).

#	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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