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NM_000298.6(PKLR):c.1529G>A (p.Arg510Gln)

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Interpretation:
Pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
11 (Most recent: Nov 19, 2021)
Last evaluated:
Dec 30, 2020
Accession:
VCV000001511.11
Variation ID:
1511
Description:
single nucleotide variant
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NM_000298.6(PKLR):c.1529G>A (p.Arg510Gln)

Allele ID
16550
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
1q22
Genomic location
1: 155291845 (GRCh38) GRCh38 UCSC
1: 155261636 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
P30613:p.Arg510Gln
NC_000001.10:g.155261636C>T
NM_181871.4:c.1436G>A NP_870986.1:p.Arg479Gln missense
... more HGVS
Protein change
R510Q, R479Q
Other names
-
Canonical SPDI
NC_000001.11:155291844:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
0.00020 (T)

Allele frequency
1000 Genomes Project 0.00020
The Genome Aggregation Database (gnomAD), exomes 0.00036
Exome Aggregation Consortium (ExAC) 0.00040
Trans-Omics for Precision Medicine (TOPMed) 0.00048
The Genome Aggregation Database (gnomAD) 0.00052
Trans-Omics for Precision Medicine (TOPMed) 0.00054
The Genome Aggregation Database (gnomAD) 0.00057
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00069
Links
ClinGen: CA215079
UniProtKB: P30613#VAR_004071
OMIM: 609712.0007
dbSNP: rs113403872
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 3 criteria provided, multiple submitters, no conflicts May 15, 2020 RCV000001575.5
Pathogenic 7 criteria provided, multiple submitters, no conflicts Dec 30, 2020 RCV000224660.7
Pathogenic 1 criteria provided, single submitter Jul 30, 2020 RCV001000208.3
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
PKLR - - GRCh38
GRCh38
GRCh37
137 160

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Jun 25, 2014)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics
Accession: SCV000280891.1
Submitted: (May 19, 2016)
Evidence details
Pathogenic
(Jun 14, 2016)
criteria provided, single submitter
Method: clinical testing
Pyruvate Kinase Deficiency
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV000348594.2
Submitted: (Oct 18, 2016)
Evidence details
Publications
PubMed (8)
Comment:
The c.1529G>A (p.Arg510Gln) variant has been described as the most common pyruvate kinase (PK) deficiency variant in the European population. Across a selection of the … (more)
Pathogenic
(Sep 06, 2018)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000863295.1
Submitted: (Sep 19, 2018)
Evidence details
Other databases
http://www.egl-eurofins.com/emvc…
Pathogenic
(Dec 21, 2015)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000329969.6
Submitted: (Jan 29, 2019)
Evidence details
Comment:
The R510Q pathogenic variant in the PKLR gene has been reported as the most common pathogenic variant association with pyruvate kinase deficiency in Northern European … (more)
Pathogenic
(Jul 30, 2020)
criteria provided, single submitter
Method: clinical testing
none provided
Allele origin: germline
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001156713.2
Submitted: (Dec 11, 2020)
Evidence details
Comment:
The PKLR c.1529G>A; p.Arg510Gln variant (rs113403872) is reported in both the homozygous or compound heterozygous state in multiple individuals affected with pyruvate kinase deficiency and … (more)
Pathogenic
(Dec 30, 2020)
criteria provided, single submitter
Method: clinical testing
Not provided
Allele origin: germline
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV001713039.1
Submitted: (May 26, 2021)
Evidence details
Publications
PubMed (6)
Pathogenic
(May 15, 2020)
criteria provided, single submitter
Method: clinical testing
Pyruvate kinase deficiency
Allele origin: germline
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego
Accession: SCV001984862.1
Submitted: (Oct 15, 2021)
Evidence details
Comment:
This variant has been previously reported as a compound heterozygous and a homozygous change in patients with (PMID: 8483951, 29396846). Functional studies on blood samples … (more)
Pathogenic
(Nov 15, 2001)
no assertion criteria provided
Method: literature only
PYRUVATE KINASE DEFICIENCY
Allele origin: germline
OMIM
Accession: SCV000021731.1
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (3)
Pathogenic
(-)
no assertion criteria provided
Method: clinical testing
not provided
Allele origin: germline
Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001930315.1
Submitted: (Sep 23, 2021)
Evidence details
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: SCV001958390.1
Submitted: (Sep 30, 2021)
Evidence details
Pathogenic
(Sep 22, 2021)
no assertion criteria provided
Method: clinical testing
not provided
Allele origin: germline
PerkinElmer Genomics
Accession: SCV002018835.1
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
Modulation of Malaria Phenotypes by Pyruvate Kinase (PKLR) Variants in a Thai Population. van Bruggen R PloS one 2015 PMID: 26658699
Erythrocyte pyruvate kinase deficiency in an old-order Amish cohort: longitudinal risk and disease management. Rider NL American journal of hematology 2011 PMID: 21815188
Pyruvate kinase deficiency: the genotype-phenotype association. Zanella A Blood reviews 2007 PMID: 17360088
Disruption of a novel regulatory element in the erythroid-specific promoter of the human PKLR gene causes severe pyruvate kinase deficiency. van Wijk R Blood 2003 PMID: 12393511
Human erythrocyte pyruvate kinase: characterization of the recombinant enzyme and a mutant form (R510Q) causing nonspherocytic hemolytic anemia. Wang C Blood 2001 PMID: 11698298
Molecular modelling of human red blood cell pyruvate kinase: structural implications of a novel G1091 to a mutation causing severe nonspherocytic hemolytic anemia. van Solinge WW Blood 1997 PMID: 9389718
Molecular analysis of 29 pyruvate kinase-deficient patients from central Europe with hereditary hemolytic anemia. Lenzner C Blood 1997 PMID: 9057665
Molecular study of pyruvate kinase deficient patients with hereditary nonspherocytic hemolytic anemia. Baronciani L The Journal of clinical investigation 1995 PMID: 7706479
Mutations in the pyruvate kinase L gene in patients with hereditary hemolytic anemia. Lenzner C Blood 1994 PMID: 8180378
Analysis of pyruvate kinase-deficiency mutations that produce nonspherocytic hemolytic anemia. Baronciani L Proceedings of the National Academy of Sciences of the United States of America 1993 PMID: 8483951
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=PKLR - - - -

Text-mined citations for rs113403872...

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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