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NM_000152.5(GAA):c.1979G>A (p.Arg660His)

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
12 (Most recent: Nov 19, 2021)
Last evaluated:
Feb 3, 2021
Accession:
VCV000189172.16
Variation ID:
189172
Description:
single nucleotide variant
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NM_000152.5(GAA):c.1979G>A (p.Arg660His)

Allele ID
187013
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
17q25.3
Genomic location
17: 80112966 (GRCh38) GRCh38 UCSC
17: 78086765 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
P10253:p.Arg660His
LRG_673:g.16411G>A
NC_000017.10:g.78086765G>A
... more HGVS
Protein change
R660H
Other names
-
Canonical SPDI
NC_000017.11:80112965:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD), exomes 0.00002
Trans-Omics for Precision Medicine (TOPMed) 0.00008
The Genome Aggregation Database (gnomAD) 0.00009
The Genome Aggregation Database (gnomAD) 0.00013
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
Trans-Omics for Precision Medicine (TOPMed) 0.00010
Exome Aggregation Consortium (ExAC) 0.00003
Links
ClinGen: CA274455
UniProtKB: P10253#VAR_046477
dbSNP: rs374143224
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 6 criteria provided, multiple submitters, no conflicts Oct 9, 2020 RCV000169600.9
Pathogenic 6 criteria provided, multiple submitters, no conflicts Feb 3, 2021 RCV000256037.8
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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
1548 1588

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Feb 04, 2015)
criteria provided, single submitter
Method: literature only
Glycogen storage disease, type II
(Autosomal recessive inheritance)
Allele origin: unknown
Counsyl
Accession: SCV000221116.1
Submitted: (Mar 11, 2015)
Evidence details
Publications
PubMed (8)
Pathogenic
(Feb 03, 2021)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000322397.6
Submitted: (Sep 25, 2021)
Evidence details
Comment:
Observed in multiple individuals with glycogen storage disease type II, who harbored a second GAA variant, in the published literature (Pipo et al., 2003; Bernstein … (more)
Pathogenic
(Feb 27, 2017)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000706386.2
Submitted: (Sep 19, 2018)
Evidence details
Publications
PubMed (7)
Other databases
http://www.egl-eurofins.com/emvc…
Pathogenic
(Oct 09, 2020)
criteria provided, single submitter
Method: clinical testing
Glycogen storage disease, type II
Allele origin: germline
Invitae
Accession: SCV000626537.3
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (7)
Comment:
This sequence change replaces arginine with histidine at codon 660 of the GAA protein (p.Arg660His). The arginine residue is highly conserved and there is a … (more)
Pathogenic
(Oct 31, 2018)
criteria provided, single submitter
Method: clinical testing
Glycogen storage disease, type II
Allele origin: unknown
Fulgent Genetics,Fulgent Genetics
Accession: SCV000894163.1
Submitted: (Nov 14, 2018)
Evidence details
Publications
PubMed (1)
DOI: 10.1038/gim.2015.30
Pathogenic
(Mar 09, 2018)
criteria provided, single submitter
Method: clinical testing
Glycogen storage disease, type II
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000917390.1
Submitted: (Apr 24, 2019)
Evidence details
Publications
PubMed (3)
Comment:
Variant summary: GAA c.1979G>A (p.Arg660His) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging … (more)
Pathogenic
(Nov 01, 2016)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
CeGaT Praxis fuer Humangenetik Tuebingen
Accession: SCV001245692.6
Submitted: (Jul 04, 2021)
Evidence details
Likely pathogenic
(Sep 26, 2019)
no assertion criteria provided
Method: clinical testing
Glycogen storage disease, type II
Allele origin: germline
Biochemical Molecular Genetic Laboratory,King Abdulaziz Medical City
Accession: SCV001133216.1
Submitted: (Sep 26, 2019)
Evidence details
Pathogenic
(Sep 16, 2020)
no assertion criteria provided
Method: clinical testing
Glycogen storage disease type II
Allele origin: germline
Natera, Inc.
Accession: SCV001459744.1
Submitted: (Dec 28, 2020)
Evidence details
Likely pathogenic
(-)
no assertion criteria provided
Method: clinical testing
not provided
Allele origin: germline
Human Genetics - Radboudumc,Radboudumc
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001956452.1
Submitted: (Sep 30, 2021)
Evidence details
Pathogenic
(-)
no assertion criteria provided
Method: clinical testing
not provided
Allele origin: germline
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001966553.1
Submitted: (Sep 21, 2021)
Evidence details
Pathogenic
(Jul 12, 2021)
no assertion criteria provided
Method: clinical testing
not provided
Allele origin: germline
PerkinElmer Genomics
Accession: SCV002021201.1
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
Late-onset pompe disease in Iran: A clinical and genetic report. Nazari F Muscle & nerve 2017 PMID: 27649523
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 Genetics in medicine : official journal of the American College of Medical Genetics 2015 PMID: 25741868
Pompe disease: literature review and case series. Dasouki M Neurologic clinics 2014 PMID: 25037089
Transcriptional response to GAA deficiency (Pompe disease) in infantile-onset patients. Palermo AT Molecular genetics and metabolism 2012 PMID: 22658377
Pediatric cardiomyopathy: importance of genetic and metabolic evaluation. Kindel SJ Journal of cardiac failure 2012 PMID: 22555271
Quantitative computed tomography for enzyme replacement therapy in Pompe disease. Yonee C Brain & development 2012 PMID: 22521436
Molecular analysis and protein processing in late-onset Pompe disease patients with low levels of acid α-glucosidase activity. Bali DS Muscle & nerve 2011 PMID: 21484825
Pompe disease: dramatic improvement in gastrointestinal function following enzyme replacement therapy. A report of three later-onset patients. Bernstein DL Molecular genetics and metabolism 2010 PMID: 20638881
Acute progression of neuromuscular findings in infantile Pompe disease. Burrow TA Pediatric neurology 2010 PMID: 20472203
The pharmacological chaperone 1-deoxynojirimycin increases the activity and lysosomal trafficking of multiple mutant forms of acid alpha-glucosidase. Flanagan JJ Human mutation 2009 PMID: 19862843
New GAA mutations in Japanese patients with GSDII (Pompe disease). Pipo JR Pediatric neurology 2003 PMID: 14643388
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=GAA - - - -

Text-mined citations for rs374143224...

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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