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NM_000152.5(GAA):c.2237G>C (p.Trp746Ser)

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
6 (Most recent: Nov 19, 2021)
Last evaluated:
Dec 20, 2018
Accession:
VCV000188484.6
Variation ID:
188484
Description:
single nucleotide variant
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NM_000152.5(GAA):c.2237G>C (p.Trp746Ser)

Allele ID
186561
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
17q25.3
Genomic location
17: 80117015 (GRCh38) GRCh38 UCSC
17: 78090814 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
P10253:p.Trp746Ser
LRG_673:g.20460G>C
LRG_673t1:c.2237G>C
... more HGVS
Protein change
W746S
Other names
-
Canonical SPDI
NC_000017.11:80117014:G:C
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Trans-Omics for Precision Medicine (TOPMed) 0.00006
Links
ClinGen: CA198797
UniProtKB: P10253#VAR_068632
dbSNP: rs752921215
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic/Likely pathogenic 5 criteria provided, multiple submitters, no conflicts Dec 20, 2018 RCV000626060.5
Likely pathogenic 1 no assertion criteria provided Oct 4, 2021 RCV001781520.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
GAA - - GRCh38
GRCh37
1547 1587

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Dec 18, 2017)
criteria provided, single submitter
Method: clinical testing
Glycogen storage disease, type II
Allele origin: inherited
Genomic Research Center,Shahid Beheshti University of Medical Sciences
Accession: SCV000746682.1
Submitted: (Dec 18, 2017)
Evidence details
Likely pathogenic
(Nov 08, 2017)
criteria provided, single submitter
Method: clinical testing
Glycogen storage disease, type II
Allele origin: unknown
Counsyl
Accession: SCV000795205.1
Submitted: (Jul 10, 2018)
Evidence details
Publications
PubMed (6)
Pathogenic
(Dec 20, 2018)
criteria provided, single submitter
Method: clinical testing
Glycogen storage disease, type II
Allele origin: germline
Invitae
Accession: SCV000950050.1
Submitted: (Mar 28, 2019)
Evidence details
Publications
PubMed (2)
Comment:
This sequence change replaces tryptophan with serine at codon 746 of the GAA protein (p.Trp746Ser). The tryptophan residue is highly conserved and there is a … (more)
Pathogenic
(Jan 22, 2020)
no assertion criteria provided
Method: curation
Glycogen storage disease, type II
(Autosomal recessive inheritance)
Allele origin: germline
Broad Institute Rare Disease Group, Broad Institute
Accession: SCV001422665.1
Submitted: (Mar 09, 2020)
Evidence details
Publications
PubMed (5)
Other databases
https://erepo.clinicalgenome.org…
Comment:
The p.Trp746Ser variant in GAA has been reported in 1 Danish, 1 Chinese, 1 Northern European, and 6 Italian individuals with Glycogen Storage Disease II … (more)
Pathogenic
(Sep 16, 2020)
no assertion criteria provided
Method: clinical testing
Glycogen storage disease type II
Allele origin: germline
Natera, Inc.
Accession: SCV001459753.1
Submitted: (Dec 28, 2020)
Evidence details
Likely pathogenic
(Oct 04, 2021)
no assertion criteria provided
Method: clinical testing
not provided
Allele origin: germline
PerkinElmer Genomics
Accession: SCV002025231.1
Submitted: (Nov 19, 2021)
Evidence details

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Skeletal muscle metabolism during prolonged exercise in Pompe disease. Preisler N Endocrine connections 2017 PMID: 28490439
[Clinical features and acid alpha-glucosidase gene mutation in 7 Chinese patients with glycogen storage disease type II]. Liu Q Zhonghua yi xue za zhi 2013 PMID: 24169249
Identification and Functional Characterization of GAA Mutations in Colombian Patients Affected by Pompe Disease. Niño MY JIMD reports 2013 PMID: 23430493
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 Human mutation 2012 PMID: 22644586
Observational clinical study in juvenile-adult glycogenosis type 2 patients undergoing enzyme replacement therapy for up to 4 years. Angelini C Journal of neurology 2012 PMID: 22081099
Update of the Pompe disease mutation database with 107 sequence variants and a format for severity rating. Kroos M Human mutation 2008 PMID: 18425781
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/23a393f7-dc57-420e-bf16-feffb9d4781b - - - -

Text-mined citations for rs752921215...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 28, 2021