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NM_000152.5(GAA):c.1003G>T (p.Gly335Trp) AND Glycogen storage disease, type II

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Aug 27, 2021
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:
RCV002030183.4

Allele description [Variation Report for NM_000152.5(GAA):c.1003G>T (p.Gly335Trp)]

NM_000152.5(GAA):c.1003G>T (p.Gly335Trp)

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.1003G>T (p.Gly335Trp)
HGVS:
  • NC_000017.11:g.80108337G>T
  • NG_009822.1:g.11782G>T
  • NM_000152.5:c.1003G>TMANE SELECT
  • NM_001079803.3:c.1003G>T
  • NM_001079804.3:c.1003G>T
  • NP_000143.2:p.Gly335Trp
  • NP_001073271.1:p.Gly335Trp
  • NP_001073272.1:p.Gly335Trp
  • LRG_673:g.11782G>T
  • NC_000017.10:g.78082136G>T
Protein change:
G335W
Links:
dbSNP: rs202095215
NCBI 1000 Genomes Browser:
rs202095215
Molecular consequence:
  • NM_000152.5:c.1003G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001079803.3:c.1003G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001079804.3:c.1003G>T - 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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002110612Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Aug 27, 2021) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Update of the pompe disease mutation database with 60 novel GAA sequence variants and additional studies on the functional effect of 34 previously reported variants.

Kroos M, Hoogeveen-Westerveld M, Michelakakis H, Pomponio R, Van der Ploeg A, Halley D, Reuser A; GAA Database Consortium..

Hum Mutat. 2012 Aug;33(8):1161-5. doi: 10.1002/humu.22108. Epub 2012 May 29.

PubMed [citation]
PMID:
22644586

Clinical course, mutations and its functional characteristics of infantile-onset Pompe disease in Thailand.

Ngiwsara L, Wattanasirichaigoon D, Tim-Aroon T, Rojnueangnit K, Noojaroen S, Khongkraparn A, Sawangareetrakul P, Ketudat-Cairns JR, Charoenwattanasatien R, Champattanachai V, Kuptanon C, Pangkanon S, Svasti J.

BMC Med Genet. 2019 Sep 11;20(1):156. doi: 10.1186/s12881-019-0878-8.

PubMed [citation]
PMID:
31510962
PMCID:
PMC6737665
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002110612.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This variant disrupts the p.Gly335 amino acid residue in GAA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22644586, 31510962). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. 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 GAA protein function. This variant has not been reported in the literature in individuals affected with GAA-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with tryptophan at codon 335 of the GAA protein (p.Gly335Trp). The glycine residue is highly conserved and there is a large physicochemical difference between glycine and tryptophan.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024