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.
ClinVar Genomic variation as it relates to human health
NM_024006.4(VKORC1):c.-1639G>A
Germline
Top reviewed classifications are shown here.
Submission summary:
Reviewed by expert panel
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_024006.4(VKORC1):c.-1639G>A
Variation ID: 2211 Accession: VCV000002211.17
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 16p11.2 16: 31096368 (GRCh38) [ NCBI UCSC ] 16: 31107689 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Apr 4, 2013 Oct 8, 2024 Nov 19, 2021 - HGVS
-
Nucleotide Protein Molecular
consequenceNC_000016.10:g.31096368C>T NC_000016.9:g.31107689C>T NG_011564.1:g.3588G>A LRG_582:g.3588G>A - Protein change
- -
- Other names
-
VKORC1, -1639G-A (rs9923231)
NM_024006.5(VKORC1):c.-1639G>T
-1639G>A
- Canonical SPDI
- NC_000016.10:31096367:C:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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.
-
0.35563 (T)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
The Genome Aggregation Database (gnomAD) 0.31157
Trans-Omics for Precision Medicine (TOPMed) 0.32269
1000 Genomes Project 30x 0.34354
1000 Genomes Project 0.35563
- Links
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 | ||
|---|---|---|---|---|---|---|
| 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. |
|||
| VKORC1 | - | - |
GRCh38 GRCh37 |
51 | 72 | |
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. |
|---|---|---|---|---|
| Pathogenic; drug response (2) |
no assertion criteria provided
|
Sep 1, 2010 | RCV000002295.15 | |
| other (1) |
criteria provided, single submitter
|
Aug 8, 2018 | RCV000377657.13 | |
| Likely benign (1) |
criteria provided, single submitter
|
Mar 9, 2018 | RCV000603173.9 | |
|
phenprocoumon response - Toxicity
|
drug response (1) |
reviewed by expert panel
|
Mar 24, 2021 | RCV001787365.11 |
| drug response (1) |
reviewed by expert panel
|
Mar 24, 2021 | RCV001787364.9 | |
|
warfarin response - Toxicity
|
drug response (1) |
reviewed by expert panel
|
Mar 24, 2021 | RCV001787366.10 |
| protective (1) |
no assertion criteria provided
|
- | RCV003150805.9 | |
| drug response (1) |
reviewed by expert panel
|
Mar 24, 2021 | RCV003227594.8 | |
| drug response (1) |
reviewed by expert panel
|
Mar 24, 2021 | RCV003227595.10 | |
|
See cases
|
Uncertain significance (1) |
no assertion criteria provided
|
- | RCV003993732.1 |
| Uncertain significance (1) |
no assertion criteria provided
|
- | RCV003996074.1 | |
| drug response (1) |
reviewed by expert panel
|
Nov 19, 2021 | RCV003227593.8 | |
|
VKORC1-related disorder
|
Likely benign (1) |
no assertion criteria provided
|
Jul 20, 2021 | RCV003952337.2 |
| click to load more click to collapse | ||||
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. |
|
|---|---|---|---|---|---|
|
drug response
Drug-variant association: Toxicity
(Mar 24, 2021)
|
reviewed by expert panel
Method: curation
|
phenprocoumon response - Toxicity
Drug used for
Hemorrhage
, over-anticoagulation
, and time above therapeutic range
Affected status: yes
Allele origin:
germline
|
PharmGKB
Accession: SCV002031258.1
First in ClinVar: Dec 12, 2021 Last updated: Dec 12, 2021
Comment:
Drug is not necessarily used to treat response condition
|
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)
|
|
|
drug response
(Mar 24, 2021)
|
reviewed by expert panel
Method: curation
|
phenprocoumon response - Dosage
Affected status: yes
Allele origin:
germline
|
PharmGKB
Accession: SCV002031257.1
First in ClinVar: Dec 12, 2021 Last updated: Dec 12, 2021 |
Comment:
PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or … (more)
PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or an FDA-approved drug label annotation. Annotations of drug labels or clinical guidelines must give prescribing guidance for specific variants (e.g. CYP2C9*3, HLA-B*57:01) or provide mapping from defined allele functions to diplotypes and phenotypes to be used as supporting evidence for a level 1A clinical annotation. Level 1A clinical annotations must also be supported by at least one publication in addition to a clinical guideline or drug label with variant-specific prescribing guidance. (less)
|
|
|
drug response
Drug-variant association: Toxicity
(Mar 24, 2021)
|
reviewed by expert panel
Method: curation
|
warfarin response - Toxicity
Drug used for
Hemorrhage
, and over-anticoagulation
Affected status: yes
Allele origin:
germline
|
PharmGKB
Accession: SCV002031259.1
First in ClinVar: Dec 12, 2021 Last updated: Dec 12, 2021
Comment:
Drug is not necessarily used to treat response condition
|
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)
|
|
|
drug response
(Nov 19, 2021)
|
reviewed by expert panel
Method: curation
|
warfarin response - Dosage
Affected status: yes
Allele origin:
germline
|
PharmGKB
Accession: SCV003925523.1
First in ClinVar: May 20, 2023 Last updated: May 20, 2023 |
Comment:
PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or … (more)
PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or an FDA-approved drug label annotation. Annotations of drug labels or clinical guidelines must give prescribing guidance for specific variants (e.g. CYP2C9*3, HLA-B*57:01) or provide mapping from defined allele functions to diplotypes and phenotypes to be used as supporting evidence for a level 1A clinical annotation. Level 1A clinical annotations must also be supported by at least one publication in addition to a clinical guideline or drug label with variant-specific prescribing guidance. (less)
|
|
|
drug response
(Mar 24, 2021)
|
reviewed by expert panel
Method: curation
|
acenocoumarol response - Dosage
Affected status: yes
Allele origin:
germline
|
PharmGKB
Accession: SCV003925522.1
First in ClinVar: May 20, 2023 Last updated: May 20, 2023 |
Comment:
PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or … (more)
PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or an FDA-approved drug label annotation. Annotations of drug labels or clinical guidelines must give prescribing guidance for specific variants (e.g. CYP2C9*3, HLA-B*57:01) or provide mapping from defined allele functions to diplotypes and phenotypes to be used as supporting evidence for a level 1A clinical annotation. Level 1A clinical annotations must also be supported by at least one publication in addition to a clinical guideline or drug label with variant-specific prescribing guidance. (less)
|
|
|
drug response
Drug-variant association: Efficacy
(Mar 24, 2021)
|
reviewed by expert panel
Method: curation
|
warfarin response - Efficacy
Drug used for
time in therapeutic range
, and time to therapeutic inr
Affected status: yes
Allele origin:
germline
|
PharmGKB
Accession: SCV003925524.1
First in ClinVar: May 20, 2023 Last updated: May 20, 2023
Comment:
Drug is not necessarily used to treat response condition
|
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)
|
|
|
other
(Aug 08, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000331715.3
First in ClinVar: Dec 06, 2016 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 481
Sex: mixed
|
|
|
Likely benign
(Mar 09, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000724152.1
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)
|
|
|
drug response
(Dec 16, 2006)
|
no assertion criteria provided
Method: clinical testing
|
Warfarin Metabolism
Affected status: not provided
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000202013.1
First in ClinVar: Jan 31, 2015 Last updated: Jan 31, 2015 |
Number of individuals with the variant: 257
|
|
|
Uncertain significance
(-)
|
no assertion criteria provided
Method: case-control
|
See cases
Affected status: yes, no
Allele origin:
germline
|
Department of Pharmacology - Sarajevo Medical School, University Sarajevo School of Science and Technology
Accession: SCV004812937.1
First in ClinVar: Apr 15, 2024 Last updated: Apr 15, 2024 |
Comment:
It is uncertain if there exists an association between the presence of the variant or A allele, at the VKORC1 -1639G>A locus, and survival from … (more)
It is uncertain if there exists an association between the presence of the variant or A allele, at the VKORC1 -1639G>A locus, and survival from thromboembolism in COVID-19 (less)
Observation 1:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (absent)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 2:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (absent)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 3:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (absent)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 4:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (absent)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 5:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (absent)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 6:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (absent)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 7:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (absent)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 8:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (absent)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 9:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (absent)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 10:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (absent)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 11:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (absent)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 12:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (absent)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 13:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (absent)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 14:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (absent)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 15:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (absent)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 16:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (absent)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 17:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (absent)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 18:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (absent)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 19:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (absent)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 20:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (absent)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 21:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (absent)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 22:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (absent)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 23:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (absent)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 24:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (absent)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 25:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (absent)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 26:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (absent)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 27:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (absent)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 28:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (absent)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 29:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (absent)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 30:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (absent)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 31:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (absent)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 32:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (absent)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 33:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (present)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 34:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (present)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 35:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (present)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 36:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (present)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 37:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (present)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 38:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (present)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 39:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (present)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 40:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (present)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 41:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (present)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 42:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (present)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 43:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (present)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 44:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (present)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 45:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (present)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 46:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (present)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 47:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (present)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
Observation 48:
Number of individuals with the variant: 1
Clinical Features:
COVID-19 (present) , Thromboembolism (present)
Method: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL); Sanger sequencing
|
|
|
Uncertain significance
(-)
|
no assertion criteria provided
Method: research, case-control
|
Thrombus
Affected status: yes, no
Allele origin:
germline
|
Department of Pharmacology - Sarajevo Medical School, University Sarajevo School of Science and Technology
Accession: SCV004807478.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024 |
Observation 1:
Number of individuals with the variant: 13
Clinical Features:
Thromboembolism (present)
Age: 31-74 years
Sex: mixed
Ethnicity/Population group: White/European
Geographic origin: Bosnia and Herzegovina
Observation 2:
Number of individuals with the variant: 21
Clinical Features:
Thromboembolism (absent)
Age: 29-77 years
Sex: mixed
Ethnicity/Population group: White/European
Geographic origin: Bosnia and Herzegovina
|
|
|
Likely benign
(Jul 20, 2021)
|
no assertion criteria provided
Method: clinical testing
|
VKORC1-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV004778777.2
First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024 |
Comment:
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
|
|
|
Pathogenic
(Sep 01, 2010)
|
no assertion criteria provided
Method: literature only
|
WARFARIN SENSITIVITY
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000022453.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Comment on evidence:
The derived -1639T or A allele (referred to differently depending on the publication) is associated with lower required warfarin dosing and higher risks of bleeding … (more)
The derived -1639T or A allele (referred to differently depending on the publication) is associated with lower required warfarin dosing and higher risks of bleeding (Ross et al., 2010). In a study to determine DNA sequence variants in 16 Chinese patients with warfarin sensitivity or resistance (122700), 104 randomly selected Chinese patients receiving warfarin, 95 normal Chinese controls, and 92 normal Caucasians, Yuan et al. (2005) identified homozygosity for a VKORC1 promoter polymorphism, -1639G-A (rs9923231), in genomic DNA of all 11 warfarin-sensitive patients. Among the 104 randomly selected Chinese patients receiving warfarin, those with the AA genotype required a lower dose than those with the AG or GG genotype (P less than 0.0001). Frequencies of AA, AG, and GG genotypes were comparable in Chinese patients receiving warfarin (79.7%, 17.6%, and 2.7%) and normal Chinese controls (82%, 18%, and 0%), but differed significantly from Caucasians (14%, 47%, and 39%) (P less than 0.0001). The promoter polymorphism abolished the E-box consensus sequences, and dual luciferase assay revealed that VKORC1 promoter with the G allele had a 44% increase of activity when compared with the A allele. The VKORC1 promoter polymorphism -1639G-A occurs frequently in patients who are warfarin-sensitive and require lower doses, whereas patients with VKORC1 missense mutations are warfarin-resistant and require higher doses. Scott et al. (2008) studied this and other polymorphisms of CYP2C9 (601130) and VKORC1 in Ashkenazi and Sephardi Jewish individuals. Unlike African Americans and similar to other individuals of European descent, the -1639A allele was present at high frequencies in both Ashkenazi (0.467) and Sephardi (0.500) cohorts. Ross et al. (2010), who referred to the VKORC1 rs9923231 polymorphism as a C-to-T change, genotyped 963 individuals from 7 geographic regions. Very low frequencies for the T allele were found in African populations (less than 10%), with the exception of the San (33%). The frequencies of the T allele were intermediate in Europe (30 to 65%), the Middle East (41 to 51%), Central/South Asia (17 to 61%), Oceania (23 to 39%), and the Americas (14 to 75%). The frequencies of the T allele were very high in East Asian populations, with frequencies ranging from 75% (She) to 100% (Han and Oroqen). Similar frequencies were found in a Canadian cohort of 316 individuals of European, East Asian, and South Asian ancestry. The findings indicated a high overall percentage (about 32%) of total variation of this allele due to genetic differences in various geographic regions. (less)
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protective
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no assertion criteria provided
Method: research
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Venous thromboembolism
Affected status: yes, no
Allele origin:
biparental
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Faculty of Pharmacy, Damascus University
Accession: SCV003836537.1
First in ClinVar: Mar 11, 2023 Last updated: Mar 11, 2023 |
Comment:
Some studies observed an association between VKORC1 -1639G>A (rs9923231) with thromboembolism (Dubovyk 2016, Kumari 2019). Our study suggests a possible protective effect for the -1639A … (more)
Some studies observed an association between VKORC1 -1639G>A (rs9923231) with thromboembolism (Dubovyk 2016, Kumari 2019). Our study suggests a possible protective effect for the -1639A allele against venous thromboembolism. References Dubovyk YI, Harbuzova VY, Ataman A V. G-1639A but Not C1173T VKORC1 Gene Polymorphism is Related to Ischemic Stroke and Its Various Risk Factors in Ukrainian Population. Biomed Res Int. 2016 Sep 15;2016. Kumari B, Garg I, Rai C, Panjawani U, Bhuvnesh K, Srivastava S. Positive Association of Mutations in VKORC1 and CYP2C9 Genes with Venous Thrombo-Embolism (VTE) in Indian Population: A Case Control Study. J Genet Eng Biotechnol Res. 2019;1(2). (less)
Observation 1:
Number of individuals with the variant: 75
Age: 17-90 years
Sex: mixed
Geographic origin: Syria
Testing laboratory: Macrogen® Inc (Seoul, South Korea)
Date variant was reported to submitter: 2020-09-10
Testing laboratory interpretation: not provided
Observation 2:
Number of individuals with the variant: 41
Age: 21-90 years
Sex: mixed
Geographic origin: Syria
Testing laboratory: Macrogen® Inc (Seoul, South Korea)
Date variant was reported to submitter: 2020-09-10
Testing laboratory interpretation: not provided
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Comment:
Comment:
PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or an FDA-approved drug label annotation. Annotations of drug labels or clinical guidelines must give prescribing guidance for specific variants (e.g. CYP2C9*3, HLA-B*57:01) or provide mapping from defined allele functions to diplotypes and phenotypes to be used as supporting evidence for a level 1A clinical annotation. Level 1A clinical annotations must also be supported by at least one publication in addition to a clinical guideline or drug label with variant-specific prescribing guidance.
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 guidance in an annotated clinical guideline or FDA drug label. Level 1B clinical annotations must be supported by at least two independent publications.
Comment:
PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or an FDA-approved drug label annotation. Annotations of drug labels or clinical guidelines must give prescribing guidance for specific variants (e.g. CYP2C9*3, HLA-B*57:01) or provide mapping from defined allele functions to diplotypes and phenotypes to be used as supporting evidence for a level 1A clinical annotation. Level 1A clinical annotations must also be supported by at least one publication in addition to a clinical guideline or drug label with variant-specific prescribing guidance.
Comment:
PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or an FDA-approved drug label annotation. Annotations of drug labels or clinical guidelines must give prescribing guidance for specific variants (e.g. CYP2C9*3, HLA-B*57:01) or provide mapping from defined allele functions to diplotypes and phenotypes to be used as supporting evidence for a level 1A clinical annotation. Level 1A clinical annotations must also be supported by at least one publication in addition to a clinical guideline or drug label with variant-specific prescribing guidance.
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 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.
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 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.
Comment:
It is uncertain if there exists an association between the presence of the variant or A allele, at the VKORC1 -1639G>A locus, and survival from thromboembolism in COVID-19
Comment:
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Comment:
Some studies observed an association between VKORC1 -1639G>A (rs9923231) with thromboembolism (Dubovyk 2016, Kumari 2019). Our study suggests a possible protective effect for the -1639A allele against venous thromboembolism. References Dubovyk YI, Harbuzova VY, Ataman A V. G-1639A but Not C1173T VKORC1 Gene Polymorphism is Related to Ischemic Stroke and Its Various Risk Factors in Ukrainian Population. Biomed Res Int. 2016 Sep 15;2016. Kumari B, Garg I, Rai C, Panjawani U, Bhuvnesh K, Srivastava S. Positive Association of Mutations in VKORC1 and CYP2C9 Genes with Venous Thrombo-Embolism (VTE) in Indian Population: A Case Control Study. J Genet Eng Biotechnol Res. 2019;1(2).
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. |
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 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.
Comment:
PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or an FDA-approved drug label annotation. Annotations of drug labels or clinical guidelines must give prescribing guidance for specific variants (e.g. CYP2C9*3, HLA-B*57:01) or provide mapping from defined allele functions to diplotypes and phenotypes to be used as supporting evidence for a level 1A clinical annotation. Level 1A clinical annotations must also be supported by at least one publication in addition to a clinical guideline or drug label with variant-specific prescribing guidance.
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 guidance in an annotated clinical guideline or FDA drug label. Level 1B clinical annotations must be supported by at least two independent publications.
Comment:
PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or an FDA-approved drug label annotation. Annotations of drug labels or clinical guidelines must give prescribing guidance for specific variants (e.g. CYP2C9*3, HLA-B*57:01) or provide mapping from defined allele functions to diplotypes and phenotypes to be used as supporting evidence for a level 1A clinical annotation. Level 1A clinical annotations must also be supported by at least one publication in addition to a clinical guideline or drug label with variant-specific prescribing guidance.
Comment:
PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or an FDA-approved drug label annotation. Annotations of drug labels or clinical guidelines must give prescribing guidance for specific variants (e.g. CYP2C9*3, HLA-B*57:01) or provide mapping from defined allele functions to diplotypes and phenotypes to be used as supporting evidence for a level 1A clinical annotation. Level 1A clinical annotations must also be supported by at least one publication in addition to a clinical guideline or drug label with variant-specific prescribing guidance.
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 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.
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 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.
Comment:
It is uncertain if there exists an association between the presence of the variant or A allele, at the VKORC1 -1639G>A locus, and survival from thromboembolism in COVID-19
Comment:
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Comment:
Some studies observed an association between VKORC1 -1639G>A (rs9923231) with thromboembolism (Dubovyk 2016, Kumari 2019). Our study suggests a possible protective effect for the -1639A allele against venous thromboembolism. References Dubovyk YI, Harbuzova VY, Ataman A V. G-1639A but Not C1173T VKORC1 Gene Polymorphism is Related to Ischemic Stroke and Its Various Risk Factors in Ukrainian Population. Biomed Res Int. 2016 Sep 15;2016. Kumari B, Garg I, Rai C, Panjawani U, Bhuvnesh K, Srivastava S. Positive Association of Mutations in VKORC1 and CYP2C9 Genes with Venous Thrombo-Embolism (VTE) in Indian Population: A Case Control Study. J Genet Eng Biotechnol Res. 2019;1(2).
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Association between VKORC1 gene polymorphism and warfarin dose requirement and frequency of VKORC1 gene polymorphism in patients from Kerman province. | Soltani Banavandi MJ | The pharmacogenomics journal | 2020 | PMID: 31902949 |
| Non-genetic factors and polymorphisms in genes CYP2C9 and VKORC1: predictive algorithms for TTR in Brazilian patients on warfarin. | Praxedes MFS | European journal of clinical pharmacology | 2020 | PMID: 31720756 |
| Algorithm for predicting low maintenance doses of warfarin using age and polymorphisms in genes CYP2C9 and VKORC1 in Brazilian subjects. | de Oliveira Magalhães Mourão A | The pharmacogenomics journal | 2020 | PMID: 31395958 |
| VKORC1 variants as significant predictors of warfarin dose in Emiratis. | Al-Mahayri ZN | Pharmacogenomics and personalized medicine | 2019 | PMID: 31114289 |
| Effects of vitamin K epoxide reductase complex 1 gene polymorphisms on warfarin control in Japanese patients with left ventricular assist devices (LVAD). | Nakagita K | European journal of clinical pharmacology | 2018 | PMID: 29781049 |
| Pharmacogenetics of vitamin K antagonists and bleeding risk prediction in atrial fibrillation. | Serna MJ | European journal of clinical investigation | 2018 | PMID: 29577257 |
| Evaluation of CYP2C9- and VKORC1-based pharmacogenetic algorithm for warfarin dose in Gaza-Palestine. | Ayesh BM | Future science OA | 2018 | PMID: 29568565 |
| Bleeding predictors in patients following venous thromboembolism treated with vitamin K antagonists: Association with increased number of single nucleotide polymorphisms. | Bryk AH | Vascular pharmacology | 2018 | PMID: 29432897 |
| Pharmacokinetic and pharmacodynamic re-evaluation of a genetic-guided warfarin trial. | Zambon CF | European journal of clinical pharmacology | 2018 | PMID: 29396738 |
| Warfarin Dose Model for the Prediction of Stable Maintenance Dose in Indian Patients. | Gaikwad T | Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis | 2018 | PMID: 28049362 |
| Genetics and clinical response to warfarin and edoxaban in patients with venous thromboembolism. | Vandell AG | Heart (British Cardiac Society) | 2017 | PMID: 28689179 |
| The impact of non-genetic and genetic factors on a stable warfarin dose in Thai patients. | Wattanachai N | European journal of clinical pharmacology | 2017 | PMID: 28550460 |
| The association between GGCX, miR-133 genetic polymorphisms and warfarin stable dosage in Han Chinese patients with mechanical heart valve replacement. | Tang XY | Journal of clinical pharmacy and therapeutics | 2017 | PMID: 28429387 |
| Assessing the relative potency of (S)- and (R)-warfarin with a new PK-PD model, in relation to VKORC1 genotypes. | Ferrari M | European journal of clinical pharmacology | 2017 | PMID: 28382498 |
| Influence of VKORC1 and CYP2C9 Polymorphisms on Daily Acenocoumarol Dose Requirement in South Indian Patients With Mechanical Heart Valves. | Kalpana SR | Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis | 2017 | PMID: 27335128 |
| VKORC1 and CYP2C9 polymorphisms related to adverse events in case-control cohort of anticoagulated patients. | Misasi S | Medicine | 2016 | PMID: 28033245 |
| G-1639A but Not C1173T VKORC1 Gene Polymorphism Is Related to Ischemic Stroke and Its Various Risk Factors in Ukrainian Population. | Dubovyk YI | BioMed research international | 2016 | PMID: 27703968 |
| 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 |
| Gene polymorphisms and the risk of warfarin-induced bleeding complications at therapeutic international normalized ratio (INR). | Pourgholi L | Toxicology and applied pharmacology | 2016 | PMID: 27581200 |
| Factors influencing quality of anticoagulation control and warfarin dosage in patients after aortic valve replacement within the 3 months of follow up. | Wypasek E | Journal of physiology and pharmacology : an official journal of the Polish Physiological Society | 2016 | PMID: 27511999 |
| Genetic determinants of warfarin maintenance dose and time in therapeutic treatment range: a RE-LY genomics substudy. | Eriksson N | Pharmacogenomics | 2016 | PMID: 27488176 |
| Effect of VKORC1, CYP2C9, CFP4F2, and GGCX Gene Polymorphisms on Warfarin Dose in Japanese Pediatric Patients. | Wakamiya T | Molecular diagnosis & therapy | 2016 | PMID: 27262824 |
| Genetic variations of phenprocoumon metabolism in patients with ventricular assist devices. | Brehm K | European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery | 2016 | PMID: 26984978 |
| Association of Genetic Polymorphisms of CYP2C9 and VKORC1 with Bleeding Following Warfarin: A Case-Control Study. | Sridharan K | Current clinical pharmacology | 2016 | PMID: 26777610 |
| A Novel Admixture-Based Pharmacogenetic Approach to Refine Warfarin Dosing in Caribbean Hispanics. | Duconge J | PloS one | 2016 | PMID: 26745506 |
| A multi-factorial analysis of response to warfarin in a UK prospective cohort. | Bourgeois S | Genome medicine | 2016 | PMID: 26739746 |
| VKORC1 gene polymorphisms and adverse events in Croatian patients on warfarin therapy. | Mandic D | International journal of clinical pharmacology and therapeutics | 2015 | PMID: 26445138 |
| 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 |
| The Influence of VKORC1 Polymorphisms on Warfarin Doses in Thai Patients with Deep Vein Thrombosis. | Sermsathanasawadi N | Journal of the Medical Association of Thailand = Chotmaihet thangphaet | 2015 | PMID: 26219158 |
| Race influences warfarin dose changes associated with genetic factors. | Limdi NA | Blood | 2015 | PMID: 26024874 |
| Genetics and the clinical response to warfarin and edoxaban: findings from the randomised, double-blind ENGAGE AF-TIMI 48 trial. | Mega JL | Lancet (London, England) | 2015 | PMID: 25769357 |
| Warfarin dosage response related pharmacogenetics in Chinese population. | Li S | PloS one | 2015 | PMID: 25594941 |
| An acenocoumarol dosing algorithm exploiting clinical and genetic factors in South Indian (Dravidian) population. | Krishna Kumar D | European journal of clinical pharmacology | 2015 | PMID: 25519826 |
| Genotype and risk of major bleeding during warfarin treatment. | Kawai VK | Pharmacogenomics | 2014 | PMID: 25521356 |
| Polymorphisms of CYP2C9, VKORC1, MDR1, APOE and UGT1A1 genes and the therapeutic warfarin dose in Brazilian patients with thrombosis: a prospective cohort study. | de Oliveira Almeida VC | Molecular diagnosis & therapy | 2014 | PMID: 25312789 |
| Pharmacogenetic association study of warfarin safety endpoints in Puerto Ricans. | Valentín II | Puerto Rico health sciences journal | 2014 | PMID: 25244877 |
| Prediction of stable acenocoumarol dose by a pharmacogenetic algorithm. | Jiménez-Varo E | Pharmacogenetics and genomics | 2014 | PMID: 25089947 |
| Methodological issues in the development of a pharmacogenomic algorithm for warfarin dosing: comparison of two regression approaches. | Pavani A | Pharmacogenomics | 2014 | PMID: 25084205 |
| Genetic determinants of acenocoumarol and warfarin maintenance dose requirements in Slavic population: a potential role of CYP4F2 and GGCX polymorphisms. | Wypasek E | Thrombosis research | 2014 | PMID: 25042728 |
| Pharmacogenetics of warfarin in a paediatric population: time in therapeutic range, initial and stable dosing and adverse effects. | Hawcutt DB | The pharmacogenomics journal | 2014 | PMID: 25001883 |
| Effect of VKORC1, CYP2C9 and CYP4F2 genetic variants in early outcomes during acenocoumarol treatment. | Cerezo-Manchado JJ | Pharmacogenomics | 2014 | PMID: 24956252 |
| Pharmacogenetics role in the safety of acenocoumarol therapy. | Jiménez-Varo E | Thrombosis and haemostasis | 2014 | PMID: 24919870 |
| The impact of age and CYP2C9 and VKORC1 variants on stable warfarin dose in the paediatric population. | Vear SI | British journal of haematology | 2014 | PMID: 24601977 |
| VKORC1 and CYP2C9 genotypes are predictors of warfarin-related outcomes in children. | Shaw K | Pediatric blood & cancer | 2014 | PMID: 24474498 |
| Characterizing variability in warfarin dose requirements in children using modelling and simulation. | Hamberg AK | British journal of clinical pharmacology | 2014 | PMID: 24330000 |
| 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 |
| Impact of genetic and clinical factors on dose requirements and quality of anticoagulation therapy in Polish patients receiving acenocoumarol: dosing calculation algorithm. | Wolkanin-Bartnik J | Pharmacogenetics and genomics | 2013 | PMID: 24108193 |
| Warfarin pharmacogenetics: a controlled dose-response study in healthy subjects. | Kadian-Dodov DL | Vascular medicine (London, England) | 2013 | PMID: 24029542 |
| Warfarin anticoagulant therapy: a Southern Italy pharmacogenetics-based dosing model. | Mazzaccara C | PloS one | 2013 | PMID: 23990957 |
| Cytochrome P450 oxidoreductase genetic polymorphisms A503V and rs2868177 do not significantly affect warfarin stable dosage in Han-Chinese patients with mechanical heart valve replacement. | Tan SL | European journal of clinical pharmacology | 2013 | PMID: 23949431 |
| Influence of CYP2C9 and VKORC1 genotypes on the risk of hemorrhagic complications in warfarin-treated patients: a systematic review and meta-analysis. | Yang J | International journal of cardiology | 2013 | PMID: 23932037 |
| An acenocoumarol dose algorithm based on a South-Eastern European population. | Pop TR | European journal of clinical pharmacology | 2013 | PMID: 23774941 |
| The bleeding risk during warfarin therapy is associated with the number of variant alleles of CYP2C9 and VKORC1 genes. | Tomek A | Cardiology | 2013 | PMID: 23774101 |
| Impact of CYP2C9 polymorphisms on the vulnerability to pharmacokinetic drug-drug interactions during acenocoumarol treatment. | Gschwind L | Pharmacogenomics | 2013 | PMID: 23651023 |
| Influence of CYP2C9 and VKORC1 gene polymorphisms on warfarin dosage, over anticoagulation and other adverse outcomes in Indian population. | Gaikwad T | European journal of pharmacology | 2013 | PMID: 23602689 |
| Cytochrome P450 (CYP2C9*2,*3) & vitamin-K epoxide reductase complex (VKORC1 -1639G<A) gene polymorphisms & their effect on acenocoumarol dose in patients with mechanical heart valve replacement. | Kaur A | The Indian journal of medical research | 2013 | PMID: 23481074 |
| Effect of CYP2C9 and VKORC1 genetic polymorphisms on mean daily maintenance dose of acenocoumarol in South Indian patients. | Krishna Kumar D | Thrombosis research | 2013 | PMID: 23473641 |
| Mechanical heart valve recipients: anticoagulation in patients with genetic variations of phenprocoumon metabolism. | Brehm K | European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery | 2013 | PMID: 23423913 |
| Randomised trial of a clinical dosing algorithm to start anticoagulation with phenprocoumon. | Caduff Good A | Swiss medical weekly | 2013 | PMID: 23299853 |
| The VKORC1 and CYP2C9 genotypes are associated with over-anticoagulation during initiation of warfarin therapy in children. | Biss TT | Journal of thrombosis and haemostasis : JTH | 2013 | PMID: 23279643 |
| The impact of the CYP2C9 and VKORC1 polymorphisms on acenocoumarol dose requirements in a Romanian population. | Buzoianu AD | Blood cells, molecules & diseases | 2013 | PMID: 23159639 |
| Impact of genetic factors (CYP2C9, VKORC1 and CYP4F2) on warfarin dose requirement in the Turkish population. | Özer M | Basic & clinical pharmacology & toxicology | 2013 | PMID: 23061746 |
| CYP2C9 and VKORC1 polymorphisms influence warfarin dose variability in patients on long-term anticoagulation. | Santos PC | European journal of clinical pharmacology | 2013 | PMID: 22990331 |
| Influence of warfarin dose-associated genotypes on the risk of hemorrhagic complications in Chinese patients on warfarin. | Ma C | International journal of hematology | 2012 | PMID: 23104259 |
| Long-term anticoagulant effects of CYP2C9 and VKORC1 genotypes in phenprocoumon users. | Verhoef TI | Journal of thrombosis and haemostasis : JTH | 2012 | PMID: 23016521 |
| An acenocoumarol dosing algorithm using clinical and pharmacogenetic data in Spanish patients with thromboembolic disease. | Borobia AM | PloS one | 2012 | PMID: 22911785 |
| Warfarin pharmacogenetics: development of a dosing algorithm for Omani patients. | Pathare A | Journal of human genetics | 2012 | PMID: 22854539 |
| Retrospective evidence for clinical validity of expanded genetic model in warfarin dose optimization in a South Indian population. | Pavani A | Pharmacogenomics | 2012 | PMID: 22676192 |
| Therapeutic dosing of acenocoumarol: proposal of a population specific pharmacogenetic dosing algorithm and its validation in north Indians. | Rathore SS | PloS one | 2012 | PMID: 22629463 |
| Oral anticoagulation and VKORC1 polymorphism in patients with a mechanical heart prosthesis: a 6-year follow-up. | Giansante C | Journal of thrombosis and thrombolysis | 2012 | PMID: 22592842 |
| Polymorphisms in VKORC1 have more impact than CYP2C9 polymorphisms on early warfarin International Normalized Ratio control and bleeding rates. | Lund K | British journal of haematology | 2012 | PMID: 22571356 |
| Impact of CYP2C9*3, VKORC1-1639, CYP4F2rs2108622 genetic polymorphism and clinical factors on warfarin maintenance dose in Han-Chinese patients. | Liang R | Journal of thrombosis and thrombolysis | 2012 | PMID: 22528326 |
| Influence of genetics and non-genetic factors on acenocoumarol maintenance dose requirement in Moroccan patients. | Smires FZ | Journal of clinical pharmacy and therapeutics | 2012 | PMID: 22486182 |
| A new warfarin dosing algorithm including VKORC1 3730 G > A polymorphism: comparison with results obtained by other published algorithms. | Cini M | European journal of clinical pharmacology | 2012 | PMID: 22349464 |
| Prediction of warfarin dose reductions in Puerto Rican patients, based on combinatorial CYP2C9 and VKORC1 genotypes. | Valentin II | The Annals of pharmacotherapy | 2012 | PMID: 22274142 |
| Association of the GGCX (CAA)16/17 repeat polymorphism with higher warfarin dose requirements in African Americans. | Cavallari LH | Pharmacogenetics and genomics | 2012 | PMID: 22158446 |
| Vitamin K antagonists in children with heart disease: height and VKORC1 genotype are the main determinants of the warfarin dose requirement. | Moreau C | Blood | 2012 | PMID: 22130800 |
| VKORC1 and CYP2C9 genotype and patient characteristics explain a large proportion of the variability in warfarin dose requirement among children. | Biss TT | Blood | 2012 | PMID: 22010099 |
| Extremely low warfarin dose in patients with genotypes of CYP2C9*3/*3 and VKORC1-1639A/A. | Gao L | Chinese medical journal | 2011 | PMID: 22040439 |
| The impact of VKORC1-1639 G>A polymorphism on the maintenance dose of oral anticoagulants for thromboembolic prophylaxis in North India: A pilot study. | Rathore SS | Indian journal of human genetics | 2011 | PMID: 21747589 |
| Loading and maintenance dose algorithms for phenprocoumon and acenocoumarol using patient characteristics and pharmacogenetic data. | van Schie RM | European heart journal | 2011 | PMID: 21636598 |
| Influence of genetic, biological and pharmacological factors on warfarin dose in a Southern Brazilian population of European ancestry. | Botton MR | British journal of clinical pharmacology | 2011 | PMID: 21320153 |
| The influence of genetic polymorphisms and interacting drugs on initial response to warfarin in Chinese patients with heart valve replacement. | Zhong SL | European journal of clinical pharmacology | 2011 | PMID: 21318593 |
| Genetic and nongenetic factors associated with warfarin dose requirements in Egyptian patients. | Shahin MH | Pharmacogenetics and genomics | 2011 | PMID: 21228733 |
| Pharmacogenomics of warfarin dose requirements in Hispanics. | Cavallari LH | Blood cells, molecules & diseases | 2011 | PMID: 21185752 |
| 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 |
| VKORC1, CYP2C9 and CYP4F2 genetic-based algorithm for warfarin dosing: an Italian retrospective study. | Zambon CF | Pharmacogenomics | 2011 | PMID: 21174619 |
| Influence of CYP2C9 and VKORC1 polymorphisms on warfarin and acenocoumarol in a sample of Lebanese people. | Esmerian MO | Journal of clinical pharmacology | 2011 | PMID: 21148049 |
| Contribution of VKORC1 and CYP2C9 polymorphisms in the interethnic variability of warfarin dose in Malaysian populations. | Gan GG | Annals of hematology | 2011 | PMID: 21110192 |
| Prediction of phenprocoumon maintenance dose and phenprocoumon plasma concentration by genetic and non-genetic parameters. | Geisen C | European journal of clinical pharmacology | 2011 | PMID: 21110013 |
| Impact of pharmacokinetic (CYP2C9) and pharmacodynamic (VKORC1, F7, GGCX, CALU, EPHX1) gene variants on the initiation and maintenance phases of phenprocoumon therapy. | Luxembourg B | Thrombosis and haemostasis | 2011 | PMID: 21057703 |
| In pediatric patients, age has more impact on dosing of vitamin K antagonists than VKORC1 or CYP2C9 genotypes. | Nowak-Göttl U | Blood | 2010 | PMID: 20833980 |
| Genome-wide association study identifies genetic determinants of warfarin responsiveness for Japanese. | Cha PC | Human molecular genetics | 2010 | PMID: 20833655 |
| CYP4F2 rs2108622: a minor significant genetic factor of warfarin dose in Han Chinese patients with mechanical heart valve replacement. | Cen HJ | British journal of clinical pharmacology | 2010 | PMID: 20653676 |
| VKORC1 V66M mutation in African Brazilian patients resistant to oral anticoagulant therapy. | Orsi FA | Thrombosis research | 2010 | PMID: 20615525 |
| Worldwide allele frequency distribution of four polymorphisms associated with warfarin dose requirements. | Ross KA | Journal of human genetics | 2010 | PMID: 20555338 |
| A regression model to predict warfarin dose from clinical variables and polymorphisms in CYP2C9, CYP4F2, and VKORC1: Derivation in a sample with predominantly a history of venous thromboembolism. | Wells PS | Thrombosis research | 2010 | PMID: 20421126 |
| Gene-based warfarin dosing compared with standard of care practices in an orthopedic surgery population: a prospective, parallel cohort study. | McMillin GA | Therapeutic drug monitoring | 2010 | PMID: 20386359 |
| VKORC1 -1639G>A and CYP2C9*3 are the major genetic predictors of phenprocoumon dose requirement. | Puehringer H | European journal of clinical pharmacology | 2010 | PMID: 20376629 |
| Integration of genetic, clinical, and INR data to refine warfarin dosing. | Lenzini P | Clinical pharmacology and therapeutics | 2010 | PMID: 20375999 |
| The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements in an adult Turkish population. | Ozer N | Heart and vessels | 2010 | PMID: 20339978 |
| 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 and clinical predictors of warfarin dose requirements in African Americans. | Cavallari LH | Clinical pharmacology and therapeutics | 2010 | PMID: 20072124 |
| Ability of VKORC1 and CYP2C9 to predict therapeutic warfarin dose during the initial weeks of therapy. | Ferder NS | Journal of thrombosis and haemostasis : JTH | 2010 | PMID: 19874474 |
| Genetic factors (VKORC1, CYP2C9, EPHX1, and CYP4F2) are predictor variables for warfarin response in very elderly, frail inpatients. | Pautas E | Clinical pharmacology and therapeutics | 2010 | PMID: 19794411 |
| A vitamin K epoxide reductase-oxidase complex gene polymorphism (-1639G>A) and interindividual variability in the dose-effect of vitamin K antagonists. | Stepien E | Journal of applied genetics | 2009 | PMID: 19875892 |
| VKORC1 diplotype-derived dosing model to explain variability in warfarin dose requirements in Asian patients. | Sandanaraj E | Drug metabolism and pharmacokinetics | 2009 | PMID: 19745563 |
| Interactive modeling for ongoing utility of pharmacogenetic diagnostic testing: application for warfarin therapy. | Linder MW | Clinical chemistry | 2009 | PMID: 19679631 |
| Influence of clinical and genetic factors on warfarin dose requirements among Japanese patients. | Ohno M | European journal of clinical pharmacology | 2009 | PMID: 19582440 |
| Exploring warfarin pharmacogenomics with the extreme-discordant-phenotype methodology: impact of FVII polymorphisms on stable anticoagulation with warfarin. | Fuchshuber-Moraes M | European journal of clinical pharmacology | 2009 | PMID: 19387626 |
| A genome-wide association study confirms VKORC1, CYP2C9, and CYP4F2 as principal genetic determinants of warfarin dose. | Takeuchi F | PLoS genetics | 2009 | PMID: 19300499 |
| Pharmacogenetics of acenocoumarol: CYP2C9 *2 and VKORC1 c.-1639G>A, 497C>G, 1173C>T, and 3730G>A variants influence drug dose in anticoagulated patients. | Verde Z | Thrombosis and haemostasis | 2009 | PMID: 19277427 |
| Estimation of the warfarin dose with clinical and pharmacogenetic data. | International Warfarin Pharmacogenetics Consortium | The New England journal of medicine | 2009 | PMID: 19228618 |
| Effect of VKORC1-1639 G>A polymorphism, body weight, age, and serum albumin alterations on warfarin response in Japanese patients. | Yoshizawa M | Thrombosis research | 2009 | PMID: 19135231 |
| Dependency of phenprocoumon dosage on polymorphisms in the VKORC1 and CYP2C9 genes. | Qazim B | Journal of thrombosis and thrombolysis | 2009 | PMID: 18629445 |
| The largest prospective warfarin-treated cohort supports genetic forecasting. | Wadelius M | Blood | 2009 | PMID: 18574025 |
| VKORC1 and CYP2C9 allelic variants influence acenocoumarol dose requirements in Greek patients. | Markatos CN | Pharmacogenomics | 2008 | PMID: 19018719 |
| The influence of polymorphisms of VKORC1 and CYP2C9 on major gastrointestinal bleeding risk in anticoagulated patients. | Montes R | British journal of haematology | 2008 | PMID: 18950464 |
| VKORC1 polymorphisms, haplotypes and haplotype groups on warfarin dose among African-Americans and European-Americans. | Limdi NA | Pharmacogenomics | 2008 | PMID: 18855533 |
| An analysis of the relative effects of VKORC1 and CYP2C9 variants on anticoagulation related outcomes in warfarin-treated patients. | Meckley LM | Thrombosis and haemostasis | 2008 | PMID: 18690342 |
| VKORC1 and CYP2C9 polymorphisms are associated with warfarin dose requirements in Turkish patients. | Oner Ozgon G | European journal of clinical pharmacology | 2008 | PMID: 18542936 |
| A genome-wide scan for common genetic variants with a large influence on warfarin maintenance dose. | Cooper GM | Blood | 2008 | PMID: 18535201 |
| Genetic determinants of response to warfarin during initial anticoagulation. | Schwarz UI | The New England journal of medicine | 2008 | PMID: 18322281 |
| Use of pharmacogenetic and clinical factors to predict the therapeutic dose of warfarin. | Gage BF | Clinical pharmacology and therapeutics | 2008 | PMID: 18305455 |
| Warfarin pharmacogenetics: CYP2C9 and VKORC1 genotypes predict different sensitivity and resistance frequencies in the Ashkenazi and Sephardi Jewish populations. | Scott SA | American journal of human genetics | 2008 | PMID: 18252229 |
| 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 |
| Estimation of warfarin maintenance dose based on VKORC1 (-1639 G>A) and CYP2C9 genotypes. | Zhu Y | Clinical chemistry | 2007 | PMID: 17510308 |
| Genotypes of vitamin K epoxide reductase, gamma-glutamyl carboxylase, and cytochrome P450 2C9 as determinants of daily warfarin dose in Japanese patients. | Kimura R | Thrombosis research | 2007 | PMID: 17049586 |
| VKORC1 gene variations are the major contributors of variation in warfarin dose in Japanese patients. | Obayashi K | Clinical pharmacology and therapeutics | 2006 | PMID: 16890578 |
| The c.-1639G > A polymorphism of the VKORC1 gene is a major determinant of the response to acenocoumarol in anticoagulated patients. | Montes R | British journal of haematology | 2006 | PMID: 16611310 |
| Influence of coagulation factor, vitamin K epoxide reductase complex subunit 1, and cytochrome P450 2C9 gene polymorphisms on warfarin dose requirements. | Aquilante CL | Clinical pharmacology and therapeutics | 2006 | PMID: 16580898 |
| The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: proposal for a new dosing regimen. | Sconce EA | Blood | 2005 | PMID: 15947090 |
| Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose. | Rieder MJ | The New England journal of medicine | 2005 | PMID: 15930419 |
| A novel functional VKORC1 promoter polymorphism is associated with inter-individual and inter-ethnic differences in warfarin sensitivity. | Yuan HY | Human molecular genetics | 2005 | PMID: 15888487 |
| Common VKORC1 and GGCX polymorphisms associated with warfarin dose. | Wadelius M | The pharmacogenomics journal | 2005 | PMID: 15883587 |
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=VKORC1 | - | - | - | - |
| https://www.pharmgkb.org/clinicalAnnotation/1447672998 | - | - | - | - |
| https://www.pharmgkb.org/clinicalAnnotation/1447673005 | - | - | - | - |
| https://www.pharmgkb.org/clinicalAnnotation/1447673015 | - | - | - | - |
| https://www.pharmgkb.org/clinicalAnnotation/1449269910 | - | - | - | - |
| https://www.pharmgkb.org/clinicalAnnotation/1451237940 | - | - | - | - |
| https://www.pharmgkb.org/clinicalAnnotation/1451243676 | - | - | - | - |
| https://www.pharmgkb.org/clinicalAnnotation/655385012 | - | - | - | - |
| https://www.pharmgkb.org/clinicalAnnotation/981204044 | - | - | - | - |
| https://www.pharmgkb.org/variant/PA166155091 | - | - | - | - |
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Text-mined citations for rs9923231 ...
HelpThese citations are identified by LitVar using
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Record last updated Nov 25, 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.