ClinVar Genomic variation as it relates to human health
NM_024006.6(VKORC1):c.174-136C>T
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_024006.6(VKORC1):c.174-136C>T
Variation ID: 37344 Accession: VCV000037344.11
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 16p11.2 16: 31093557 (GRCh38) [ NCBI UCSC ] 16: 31104878 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Aug 24, 2013 Dec 12, 2021 Mar 29, 2021 - HGVS
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Nucleotide Protein Molecular
consequenceNM_024006.6:c.174-136C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
intron variant NM_001311311.2:c.174-136C>T intron variant NM_206824.3:c.173+1000C>T intron variant NC_000016.10:g.31093557G>A NC_000016.9:g.31104878G>A NG_011564.1:g.6399C>T LRG_582:g.6399C>T LRG_582t1:c.174-136C>T - Protein change
- Other names
- VKORC1: 1173C>T
- Canonical SPDI
- NC_000016.10:31093556:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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0.35583 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.31147
Trans-Omics for Precision Medicine (TOPMed) 0.32276
1000 Genomes Project 30x 0.34385
1000 Genomes Project 0.35583
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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VKORC1 | - | - |
GRCh38 GRCh37 |
47 | 71 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic; drug response (2) |
no assertion criteria provided
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Aug 31, 2010 | RCV000054531.14 | |
drug response (1) |
reviewed by expert panel
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Mar 29, 2021 | RCV000211147.11 | |
drug response (1) |
reviewed by expert panel
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Mar 24, 2021 | RCV000211275.11 | |
Benign (1) |
criteria provided, single submitter
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Jun 14, 2016 | RCV000291997.13 | |
Likely benign (1) |
criteria provided, single submitter
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Mar 9, 2018 | RCV000616307.9 | |
drug response (1) |
reviewed by expert panel
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Mar 24, 2021 | RCV001787818.9 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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drug response
(Mar 24, 2021)
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reviewed by expert panel
Method: curation
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acenocoumarol response - Dosage
Affected status: yes
Allele origin:
germline
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PharmGKB
Accession: SCV000268423.4
First in ClinVar: May 22, 2016 Last updated: Dec 12, 2021 |
Comment:
PharmGKB Level of Evidence 2A: Variants in Level 2A clinical annotations are found in PharmGKB’s Tier 1 Very Important Pharmacogenes (VIPs). These variants are in … (more)
PharmGKB Level of Evidence 2A: Variants in Level 2A clinical annotations are found in PharmGKB’s Tier 1 Very Important Pharmacogenes (VIPs). These variants are in known pharmacogenes, implying causation of drug phenotype is more likely. These clinical annotations describe variant-drug combinations with a moderate level of evidence supporting the association. For example, the association may be found in multiple cohorts, but there may be a minority of studies that do not support the majority assertion. Level 2A clinical annotations must be supported by at least two independent publications. (less)
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drug response
(Mar 24, 2021)
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reviewed by expert panel
Method: curation
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phenprocoumon response - Dosage
Affected status: yes
Allele origin:
germline
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PharmGKB
Accession: SCV002031260.1
First in ClinVar: Dec 12, 2021 Last updated: Dec 12, 2021 |
Comment:
PharmGKB Level of Evidence 2A: Variants in Level 2A clinical annotations are found in PharmGKB’s Tier 1 Very Important Pharmacogenes (VIPs). These variants are in … (more)
PharmGKB Level of Evidence 2A: Variants in Level 2A clinical annotations are found in PharmGKB’s Tier 1 Very Important Pharmacogenes (VIPs). These variants are in known pharmacogenes, implying causation of drug phenotype is more likely. These clinical annotations describe variant-drug combinations with a moderate level of evidence supporting the association. For example, the association may be found in multiple cohorts, but there may be a minority of studies that do not support the majority assertion. Level 2A clinical annotations must be supported by at least two independent publications. (less)
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drug response
(Mar 29, 2021)
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reviewed by expert panel
Method: curation
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warfarin response - Dosage
Affected status: yes
Allele origin:
germline
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PharmGKB
Accession: SCV000268422.4
First in ClinVar: May 22, 2016 Last updated: Dec 12, 2021 |
Comment:
PharmGKB Level of Evidence 1B: Level 1B clinical annotations describe variant-drug combinations with a high level of evidence supporting the association but no variant-specific prescribing … (more)
PharmGKB Level of Evidence 1B: Level 1B clinical annotations describe variant-drug combinations with a high level of evidence supporting the association but no variant-specific prescribing guidance in an annotated clinical guideline or FDA drug label. Level 1B clinical annotations must be supported by at least two independent publications. (less)
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Benign
(Jun 14, 2016)
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criteria provided, single submitter
Method: clinical testing
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Vitamin K-Dependent Clotting Factors
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000396620.2
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
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Likely benign
(Mar 09, 2018)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000730674.1
First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
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drug response
(Aug 31, 2010)
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no assertion criteria provided
Method: research
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Warfarin response
Drug used for
hemorrhage
Affected status: no
Allele origin:
unknown
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Pharmacogenomics Lab, Chungbuk National University
Accession: SCV000889936.1
First in ClinVar: Sep 08, 2019 Last updated: Sep 08, 2019 |
Number of individuals with the variant: 140
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Pathogenic
(Oct 01, 2008)
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no assertion criteria provided
Method: literature only
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WARFARIN SENSITIVITY
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000083009.1
First in ClinVar: Aug 24, 2013 Last updated: Aug 24, 2013 |
Comment on evidence:
Among 273 African Americans and 302 European Americans undergoing warfarin therapy, Limdi et al. (2008) found that variation in the VKORC1 gene could explain 5% … (more)
Among 273 African Americans and 302 European Americans undergoing warfarin therapy, Limdi et al. (2008) found that variation in the VKORC1 gene could explain 5% and 18% variability, respectively, in warfarin dosage. Two SNPs in the VKORC1 gene, rs9934438 and rs9923231 (608547.0006), were the best predictors of warfarin dose among both groups. (less)
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Germline Functional Evidence
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 germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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The effect of genetic and nongenetic factors on warfarin dose variability in Qatari population. | Bader L | The pharmacogenomics journal | 2020 | PMID: 31653973 |
APOB gene polymorphisms may affect the risk of minor or minimal bleeding complications in patients on warfarin maintaining therapeutic INR. | Yee J | European journal of human genetics : EJHG | 2019 | PMID: 31186542 |
Extremely low therapeutic doses of acenocoumarol in a patient with CYP2C9*3/*3 and VKORC1-1639A/A genotype. | Chaidaroglou A | Pharmacogenomics | 2019 | PMID: 30983536 |
Effects of age and genetic variations in VKORC1, CYP2C9 and CYP3A4 on the phenprocoumon dose in pediatric patients. | Maagdenberg H | Pharmacogenomics | 2018 | PMID: 30207196 |
Polymorphisms of vitamin K-related genes (EPHX1 and VKORC1L1) and stable warfarin doses. | Chung JE | Gene | 2018 | PMID: 29054760 |
Influence of NR3C1 and VDR polymorphisms on stable warfarin dose in patients with mechanical cardiac valves. | Lee KE | International journal of cardiology | 2017 | PMID: 28262345 |
Genetic polymorphisms of patients on stable warfarin maintenance therapy in a Ghanaian population. | Kudzi W | BMC research notes | 2016 | PMID: 27938396 |
Impact of CYP2C9, VKORC1 and CYP4F2 genetic polymorphisms on maintenance warfarin dosage in Han-Chinese patients: A systematic review and meta-analysis. | Zhang J | Meta gene | 2016 | PMID: 27617219 |
An expanded pharmacogenomics warfarin dosing table with utility in generalised dosing guidance. | Shahabi P | Thrombosis and haemostasis | 2016 | PMID: 27121899 |
Development and Comparison of Warfarin Dosing Algorithms in Stroke Patients. | Cho SM | Yonsei medical journal | 2016 | PMID: 26996562 |
The influence of VKORC1 gene polymorphism on warfarin maintenance dosage in pediatric patients: A systematic review and meta-analysis. | Zhang J | Thrombosis research | 2015 | PMID: 26433837 |
Effects of NAD(P)H quinone oxidoreductase 1 polymorphisms on stable warfarin doses in Korean patients with mechanical cardiac valves. | Chung JE | European journal of clinical pharmacology | 2015 | PMID: 26257249 |
Influence of UDP-Glucuronosyltransferase Polymorphisms on Stable Warfarin Doses in Patients with Mechanical Cardiac Valves. | An SH | Cardiovascular therapeutics | 2015 | PMID: 26223945 |
Clinical Application of Genotype-guided Dosing of Warfarin in Patients with Acute Stroke. | Šupe S | Archives of medical research | 2015 | PMID: 25989350 |
Impact of GATA4 variants on stable warfarin doses in patients with prosthetic heart valves. | Jeong E | The pharmacogenomics journal | 2015 | PMID: 25026456 |
Verification of pharmacogenetics-based warfarin dosing algorithms in Han-Chinese patients undertaking mechanic heart valve replacement. | Zhao L | PloS one | 2014 | PMID: 24728385 |
A new algorithm for weekly phenprocoumon dose variation in a southern Brazilian population: role for CYP2C9, CYP3A4/5 and VKORC1 genes polymorphisms. | Botton MR | Basic & clinical pharmacology & toxicology | 2014 | PMID: 24224579 |
Effect of CYP2C9, VKORC1, CYP4F2 and GGCX genetic variants on warfarin maintenance dose and explicating a new pharmacogenetic algorithm in South Indian population. | Krishna Kumar D | European journal of clinical pharmacology | 2014 | PMID: 24019055 |
Warfarin anticoagulant therapy: a Southern Italy pharmacogenetics-based dosing model. | Mazzaccara C | PloS one | 2013 | PMID: 23990957 |
Genetic and clinical determinants influencing warfarin dosing in children with heart disease. | Nguyen N | Pediatric cardiology | 2013 | PMID: 23183958 |
The influence of VKORC1 and CYP2C9 gene sequence variants on the stability of maintenance phase warfarin treatment. | Skov J | Thrombosis research | 2013 | PMID: 23159229 |
Validation of the acenocoumarol EU-PACT algorithms: similar performance in the Rotterdam Study cohort as in the original study. | van Schie RM | Pharmacogenomics | 2012 | PMID: 22920394 |
Effects of CYP4F2 gene polymorphisms on warfarin clearance and sensitivity in Korean patients with mechanical cardiac valves. | Lee KE | Therapeutic drug monitoring | 2012 | PMID: 22549502 |
A new algorithm to predict warfarin dose from polymorphisms of CYP4F2 , CYP2C9 and VKORC1 and clinical variables: derivation in Han Chinese patients with non valvular atrial fibrillation. | Wei M | Thrombosis and haemostasis | 2012 | PMID: 22534826 |
Genetic polymorphisms are associated with variations in warfarin maintenance dose in Han Chinese patients with venous thromboembolism. | Zhang W | Pharmacogenomics | 2012 | PMID: 22248286 |
The effect of CYP2C9, VKORC1 genotypes and old age on warfarin pharmacologic sensitivity in korean patients with thromboembolic disease. | Moon HW | Annals of clinical and laboratory science | 2011 | PMID: 22075505 |
Development and comparison of a warfarin-dosing algorithm for Korean patients with atrial fibrillation. | Cho HJ | Clinical therapeutics | 2011 | PMID: 21981797 |
Proposal of pharmacogenetics-based warfarin dosing algorithm in Korean patients. | Choi JR | Journal of human genetics | 2011 | PMID: 21326313 |
Effect of the VKORC1 genotype on warfarin dose requirements in Japanese pediatric patients. | Kato Y | Drug metabolism and pharmacokinetics | 2011 | PMID: 21273734 |
Contribution of 1173C > T polymorphism in the VKORC1 gene to warfarin dose requirements in Han Chinese patients receiving anticoagulation. | Yang J | International journal of clinical pharmacology and therapeutics | 2011 | PMID: 21176721 |
Warfarin dosing algorithm using clinical, demographic and pharmacogenetic data from Chinese patients. | You JH | Journal of thrombosis and thrombolysis | 2011 | PMID: 20585834 |
Warfarin pharmacogenetics: a single VKORC1 polymorphism is predictive of dose across 3 racial groups. | Limdi NA | Blood | 2010 | PMID: 20203262 |
Comparative performance of gene-based warfarin dosing algorithms in a multiethnic population. | Lubitz SA | Journal of thrombosis and haemostasis : JTH | 2010 | PMID: 20128861 |
Genetic determinants of acenocoumarol and phenprocoumon maintenance dose requirements. | Cadamuro J | European journal of clinical pharmacology | 2010 | PMID: 20020283 |
Influence of CYP2C9 and VKORC1 on warfarin response during initiation of therapy. | Limdi NA | Blood cells, molecules & diseases | 2009 | PMID: 19297219 |
Pharmacogenetic relevance of CYP4F2 V433M polymorphism on acenocoumarol therapy. | Pérez-Andreu V | Blood | 2009 | PMID: 19270263 |
Genotypes associated with reduced activity of VKORC1 and CYP2C9 and their modification of acenocoumarol anticoagulation during the initial treatment period. | Teichert M | Clinical pharmacology and therapeutics | 2009 | PMID: 19225451 |
Validation of VKORC1 and CYP2C9 genotypes on interindividual warfarin maintenance dose: a prospective study in Chinese patients. | Huang SW | Pharmacogenetics and genomics | 2009 | PMID: 19177029 |
Effect of CYP2C9 and VKORC1 genotypes on early-phase and steady-state warfarin dosing in Korean patients with mechanical heart valve replacement. | Kim HS | Pharmacogenetics and genomics | 2009 | PMID: 19077919 |
Relative contribution of CYP2C9 and VKORC1 genotypes and early INR response to the prediction of warfarin sensitivity during initiation of therapy. | Li C | Blood | 2009 | PMID: 19074728 |
VKORC1 polymorphisms, haplotypes and haplotype groups on warfarin dose among African-Americans and European-Americans. | Limdi NA | Pharmacogenomics | 2008 | PMID: 18855533 |
Effects of CYP2C9 and VKORC1 on INR variations and dose requirements during initial phase of anticoagulant therapy. | Spreafico M | Pharmacogenomics | 2008 | PMID: 18781852 |
Influence of CYP2C9 and VKORC1 on warfarin dose, anticoagulation attainment and maintenance among European-Americans and African-Americans. | Limdi NA | Pharmacogenomics | 2008 | PMID: 18466099 |
Combination of phenotype assessments and CYP2C9-VKORC1 polymorphisms in the determination of warfarin dose requirements in heavily medicated patients. | Michaud V | Clinical pharmacology and therapeutics | 2008 | PMID: 18030307 |
Ethnic differences in the VKORC1 gene polymorphism and an association with warfarin dosage requirements in cardiovascular surgery patients. | Nakai K | Pharmacogenomics | 2007 | PMID: 18240904 |
Randomized trial of genotype-guided versus standard warfarin dosing in patients initiating oral anticoagulation. | Anderson JL | Circulation | 2007 | PMID: 17989110 |
The genetic interaction between VKORC1 c1173t and calumenin a29809g modulates the anticoagulant response of acenocoumarol. | González-Conejero R | Journal of thrombosis and haemostasis : JTH | 2007 | PMID: 17596133 |
Factors affecting the interindividual variability of warfarin dose requirement in adult Korean patients. | Cho HJ | Pharmacogenomics | 2007 | PMID: 17391071 |
Warfarin response and vitamin K epoxide reductase complex 1 in African Americans and Caucasians. | Schelleman H | Clinical pharmacology and therapeutics | 2007 | PMID: 17329985 |
Genotypes of the cytochrome p450 isoform, CYP2C9, and the vitamin K epoxide reductase complex subunit 1 conjointly determine stable warfarin dose: a prospective study. | Carlquist JF | Journal of thrombosis and thrombolysis | 2006 | PMID: 17111199 |
1173C>T polymorphism in VKORC1 modulates the required warfarin dose. | Kosaki K | Pediatric cardiology | 2006 | PMID: 17031720 |
Multiple gene polymorphisms and warfarin sensitivity. | Shikata E | European journal of clinical pharmacology | 2006 | PMID: 16821005 |
VKORC1 and CYP2C9 genotypes and acenocoumarol anticoagulation status: interaction between both genotypes affects overanticoagulation. | Schalekamp T | Clinical pharmacology and therapeutics | 2006 | PMID: 16815313 |
The influence of sequence variations in factor VII, gamma-glutamyl carboxylase and vitamin K epoxide reductase complex genes on warfarin dose requirement. | Herman D | Thrombosis and haemostasis | 2006 | PMID: 16676068 |
Polymorphisms in the VKORC1 gene are strongly associated with warfarin dosage requirements in patients receiving anticoagulation. | Li T | Journal of medical genetics | 2006 | PMID: 16611750 |
Association of VKORC1 and CYP2C9 polymorphisms with warfarin dose requirements in Japanese patients. | Mushiroda T | Journal of human genetics | 2006 | PMID: 16432637 |
VKORC1 haplotypes and their impact on the inter-individual and inter-ethnical variability of oral anticoagulation. | Geisen C | Thrombosis and haemostasis | 2005 | PMID: 16270629 |
A C1173T dimorphism in the VKORC1 gene determines coumarin sensitivity and bleeding risk. | Reitsma PH | PLoS medicine | 2005 | PMID: 16201835 |
Common VKORC1 and GGCX polymorphisms associated with warfarin dose. | Wadelius M | The pharmacogenomics journal | 2005 | PMID: 15883587 |
A polymorphism in the VKORC1 gene is associated with an interindividual variability in the dose-anticoagulant effect of warfarin. | D'Andrea G | Blood | 2005 | PMID: 15358623 |
https://www.pharmgkb.org/clinicalAnnotation/1183704228 | - | - | - | - |
https://www.pharmgkb.org/clinicalAnnotation/1451244040 | - | - | - | - |
https://www.pharmgkb.org/clinicalAnnotation/655385392 | - | - | - | - |
https://www.pharmgkb.org/variant/PA166155096 | - | - | - | - |
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Text-mined citations for rs9934438 ...
HelpRecord last updated Mar 23, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.