ClinVar Genomic variation as it relates to human health
CYP2C9*3
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
-
CYP2C9*3
Variation ID: 8408 Accession: VCV000008408.13
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 10q23.33 10: 94981296 (GRCh38) [ NCBI UCSC ] 10: 96741053 (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 Nov 17, 2024 Feb 11, 2019 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000771.4:c.1075A>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000762.2:p.Ile359Leu missense NC_000010.11:g.94981296A>C NC_000010.10:g.96741053A>C NG_008385.2:g.48139A>C LRG_1195:g.48139A>C LRG_1195t1:c.1075A>C LRG_1195p1:p.Ile359Leu P11712:p.Ile359Leu - Protein change
- I359L
- Other names
-
NM_000771.3(CYP2C9):c.1075A>C (p.Ile359Leu)
CYP2C9, ILE359LEU (rs1057910)
1075A>C
- Canonical SPDI
- NC_000010.11:94981295:A:C
-
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.
-
0.04852 (C)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
Trans-Omics for Precision Medicine (TOPMed) 0.04520
1000 Genomes Project 30x 0.04575
1000 Genomes Project 0.04852
The Genome Aggregation Database (gnomAD) 0.04900
Exome Aggregation Consortium (ExAC) 0.06371
- Links
-
PharmGKB Clinical Annotation: 655384720 PharmGKB Clinical Annotation: 769181841 PharmGKB Clinical Annotation: 827862258 PharmGKB Clinical Annotation: 981238437 ClinGen: CA119590 Genetic Testing Registry (GTR): GTR000569522 Genetic Testing Registry (GTR): GTR000613302 Genetic Testing Registry (GTR): GTR000613428 UniProtKB: P11712#VAR_008345 OMIM: 601130.0001 dbSNP: rs1057910 VarSome
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. |
|||
CYP2C9 | - | - |
GRCh38 GRCh37 |
37 | 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. |
---|---|---|---|---|
drug response (3) |
no assertion criteria provided
|
Jun 15, 2012 | RCV000008917.13 | |
drug response (2) |
no assertion criteria provided
|
Sep 24, 2020 | RCV000008918.12 | |
drug response (1) |
no assertion criteria provided
|
Jun 15, 2012 | RCV000008919.11 | |
drug response (1) |
no assertion criteria provided
|
Dec 30, 2010 | RCV000008916.9 | |
other (1) |
criteria provided, single submitter
|
Jul 10, 2015 | RCV000339502.12 | |
drug response (1) |
criteria provided, single submitter
|
Feb 11, 2019 | RCV000787930.10 | |
drug response (1) |
criteria provided, single submitter
|
Feb 11, 2019 | RCV000788100.10 | |
drug response (1) |
criteria provided, single submitter
|
Feb 11, 2019 | RCV000788094.10 |
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. |
|
---|---|---|---|---|---|
other
(Jul 10, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000331714.3
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
Number of individuals with the variant: 113
Zygosity: Homozygote, Single Heterozygote
Sex: mixed
|
|
drug response
(Feb 11, 2019)
|
criteria provided, single submitter
Method: curation
|
Lesinurad response
Drug used for
Gout
Affected status: yes
Allele origin:
germline
|
Medical Genetics Summaries
Accession: SCV000927092.1
First in ClinVar: Jul 24, 2019 Last updated: Jul 24, 2019 |
Comment:
Lesinurad should be used with caution in individuals with 2 decreased function alleles (CYP2C9 poor metabolizers) because of increased exposure and an increased risk of … (more)
Lesinurad should be used with caution in individuals with 2 decreased function alleles (CYP2C9 poor metabolizers) because of increased exposure and an increased risk of side effects. (less)
|
|
drug response
(Feb 11, 2019)
|
criteria provided, single submitter
Method: curation
|
Flurbiprofen response
Drug used for
Pain
, Inflammation
, Osteoarthritis
, Rheumatoid Arthritis
, Bursitis
, and Tendinitis
Affected status: yes
Allele origin:
germline
|
Medical Genetics Summaries
Accession: SCV000926949.1
First in ClinVar: Jul 21, 2019 Last updated: Jul 21, 2019 |
Comment:
The dose of flurbiprofen should be reduced in individuals with 2 decreased function alleles (CYP2C9 poor metabolizers) to avoid abnormally high plasma levels due to … (more)
The dose of flurbiprofen should be reduced in individuals with 2 decreased function alleles (CYP2C9 poor metabolizers) to avoid abnormally high plasma levels due to reduced metabolic clearance. (less)
|
|
drug response
(Feb 11, 2019)
|
criteria provided, single submitter
Method: curation
|
Piroxicam response
Drug used for
Pain
, Inflammation
, Osteoarthritis
, and Rheumatoid arthritis
Affected status: yes
Allele origin:
germline
|
Medical Genetics Summaries
Accession: SCV000927098.1
First in ClinVar: Jul 24, 2019 Last updated: Jul 24, 2019 |
Comment:
Individuals with 2 decreased function alleles (CYP2C9 poor metabolizers) have reduced clearance of piroxicam. Because the standard recommended dose of piroxicam may cause abnormally high … (more)
Individuals with 2 decreased function alleles (CYP2C9 poor metabolizers) have reduced clearance of piroxicam. Because the standard recommended dose of piroxicam may cause abnormally high plasma levels, a dose reduction should be considered for these individuals. (less)
|
|
drug response
(Jun 15, 2012)
|
no assertion criteria provided
Method: literature only
|
PHENYTOIN POOR METABOLIZER
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000029128.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Comment on evidence:
The ile359-to-leu (I359L) substitution results from a 1075A-C transversion in the CYP2C9 gene and is also known as rs1057910 and CYP2C9*3. The variant leads to … (more)
The ile359-to-leu (I359L) substitution results from a 1075A-C transversion in the CYP2C9 gene and is also known as rs1057910 and CYP2C9*3. The variant leads to reduced warfarin metabolism and increased risk of bleeding (Ross et al., 2010). Extensive interindividual variation in the response to a given dose Sullivan-Klose et al. (1996) demonstrated that the form of CYP2C9 in which ile359 is replaced by leucine is the basis of poor metabolizing of tolbutamide, the sulfonylurea hypoglycemic agent used in the treatment of diabetes mellitus (NIDDM; 125853). The frequency of the leu359 allele was found to be 0.06 in the Caucasian-American population and 0.005 in African Americans. The frequency of the leu359 allele was 0.026 in Chinese-Taiwanese. They found that the leu359 allelic variant of CYP2C9 also has a lower affinity and a lower intrinsic clearance for S-warfarin 7-hydroxylation than the ile359 variant. Presumably, 7-hydroxylation has an important role in terminating the anticoagulant activity of warfarin in vitro, and individuals who are homozygous for the leu359 variant might require lower doses of this anticoagulant. In a patient who was unusually sensitive to warfarin therapy (see 122700), Steward et al. (1997) identified homozygosity for I359L, the so-called CYP2C9*3 allele. The patient, who was taking 0.5 mg of warfarin daily, had an S-to-R enantiomer ratio of 3.9:1, whereas control patients taking 4 to 8 mg of warfarin daily had S-to-R ratios of about 0.5:1. Steward et al. (1997) concluded that expression of CYP2C9*3 is associated with diminished clearance of the more potent S-warfarin, and that analysis of the plasma S-to-R warfarin ratio might serve as a useful alternative test to genotyping. Kidd et al. (1999) described a 29-year-old male Caucasian who had participated in 6 bioequivalence studies over a period of several years. The patient displayed severe hypoglycemia after a single dose of glipizide, a second generation sulfonylurea structurally similar to tolbutamide and used as an oral hypoglycemic agent. His oral clearance of phenytoin was 21% of the mean of 11 other individuals, and his oral clearance of glipizide was only 18% of the mean of 10 other individuals. His oral clearance of nifedipine (a CYP3A4 (124010) substrate) and chlorpheniramine (a CYP2D6 (see 124030) substrate) did not differ from that of other individuals studied. Genotype testing demonstrated that the individual was homozygous for the leu359 allele and did not possess any of the known defective CYP2C19 (124020) alleles. These studies established that the leu359 allele is responsible for the phenytoin and glipizide/tolbutamide poor metabolizer phenotype. In a study of 281 epileptic patients treated with phenytoin, Tate et al. (2005) found a significant association between the maximum dose needed and the CYP2C9*3 allele (I359L). Mean phenytoin doses for individuals with 0, 1, or 2 copies of the *3 allele were 354, 309, and 250 mg, respectively, indicating a trend of reduction in maximum dose needed to control symptoms. Ross et al. (2010) genotyped 963 individuals from 7 geographic regions for the CYP2C9*3 variant. The highest frequencies were observed in Europe (4 to 21%), the Middle East (3 to 11%) and Central/South Asia (5 to 15%). The allele was not observed in Africa or most populations from the Americas, except the Pima (7%). In Oceania, the allele was not present in Melanesians, but in Papua New Guinea the frequency was 12%. The allele was absent in many populations in East Asia, but reached frequencies of 10% or higher in some populations, such as the Tu, Tujia and Xibo. Similar frequencies were found in a Canadian cohort of 316 individuals of European, East Asian, and South Asian ancestry. (less)
|
|
drug response
(Jun 15, 2012)
|
no assertion criteria provided
Method: literature only
|
GLIPIZIDE POOR METABOLIZER
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000029129.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Comment on evidence:
The ile359-to-leu (I359L) substitution results from a 1075A-C transversion in the CYP2C9 gene and is also known as rs1057910 and CYP2C9*3. The variant leads to … (more)
The ile359-to-leu (I359L) substitution results from a 1075A-C transversion in the CYP2C9 gene and is also known as rs1057910 and CYP2C9*3. The variant leads to reduced warfarin metabolism and increased risk of bleeding (Ross et al., 2010). Extensive interindividual variation in the response to a given dose Sullivan-Klose et al. (1996) demonstrated that the form of CYP2C9 in which ile359 is replaced by leucine is the basis of poor metabolizing of tolbutamide, the sulfonylurea hypoglycemic agent used in the treatment of diabetes mellitus (NIDDM; 125853). The frequency of the leu359 allele was found to be 0.06 in the Caucasian-American population and 0.005 in African Americans. The frequency of the leu359 allele was 0.026 in Chinese-Taiwanese. They found that the leu359 allelic variant of CYP2C9 also has a lower affinity and a lower intrinsic clearance for S-warfarin 7-hydroxylation than the ile359 variant. Presumably, 7-hydroxylation has an important role in terminating the anticoagulant activity of warfarin in vitro, and individuals who are homozygous for the leu359 variant might require lower doses of this anticoagulant. In a patient who was unusually sensitive to warfarin therapy (see 122700), Steward et al. (1997) identified homozygosity for I359L, the so-called CYP2C9*3 allele. The patient, who was taking 0.5 mg of warfarin daily, had an S-to-R enantiomer ratio of 3.9:1, whereas control patients taking 4 to 8 mg of warfarin daily had S-to-R ratios of about 0.5:1. Steward et al. (1997) concluded that expression of CYP2C9*3 is associated with diminished clearance of the more potent S-warfarin, and that analysis of the plasma S-to-R warfarin ratio might serve as a useful alternative test to genotyping. Kidd et al. (1999) described a 29-year-old male Caucasian who had participated in 6 bioequivalence studies over a period of several years. The patient displayed severe hypoglycemia after a single dose of glipizide, a second generation sulfonylurea structurally similar to tolbutamide and used as an oral hypoglycemic agent. His oral clearance of phenytoin was 21% of the mean of 11 other individuals, and his oral clearance of glipizide was only 18% of the mean of 10 other individuals. His oral clearance of nifedipine (a CYP3A4 (124010) substrate) and chlorpheniramine (a CYP2D6 (see 124030) substrate) did not differ from that of other individuals studied. Genotype testing demonstrated that the individual was homozygous for the leu359 allele and did not possess any of the known defective CYP2C19 (124020) alleles. These studies established that the leu359 allele is responsible for the phenytoin and glipizide/tolbutamide poor metabolizer phenotype. In a study of 281 epileptic patients treated with phenytoin, Tate et al. (2005) found a significant association between the maximum dose needed and the CYP2C9*3 allele (I359L). Mean phenytoin doses for individuals with 0, 1, or 2 copies of the *3 allele were 354, 309, and 250 mg, respectively, indicating a trend of reduction in maximum dose needed to control symptoms. Ross et al. (2010) genotyped 963 individuals from 7 geographic regions for the CYP2C9*3 variant. The highest frequencies were observed in Europe (4 to 21%), the Middle East (3 to 11%) and Central/South Asia (5 to 15%). The allele was not observed in Africa or most populations from the Americas, except the Pima (7%). In Oceania, the allele was not present in Melanesians, but in Papua New Guinea the frequency was 12%. The allele was absent in many populations in East Asia, but reached frequencies of 10% or higher in some populations, such as the Tu, Tujia and Xibo. Similar frequencies were found in a Canadian cohort of 316 individuals of European, East Asian, and South Asian ancestry. (less)
|
|
drug response
(Dec 30, 2010)
|
no assertion criteria provided
Method: literature only
|
TOLBUTAMIDE POOR METABOLIZER
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000029126.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Comment on evidence:
The ile359-to-leu (I359L) substitution results from a 1075A-C transversion in the CYP2C9 gene and is also known as rs1057910 and CYP2C9*3. The variant leads to … (more)
The ile359-to-leu (I359L) substitution results from a 1075A-C transversion in the CYP2C9 gene and is also known as rs1057910 and CYP2C9*3. The variant leads to reduced warfarin metabolism and increased risk of bleeding (Ross et al., 2010). Extensive interindividual variation in the response to a given dose Sullivan-Klose et al. (1996) demonstrated that the form of CYP2C9 in which ile359 is replaced by leucine is the basis of poor metabolizing of tolbutamide, the sulfonylurea hypoglycemic agent used in the treatment of diabetes mellitus (NIDDM; 125853). The frequency of the leu359 allele was found to be 0.06 in the Caucasian-American population and 0.005 in African Americans. The frequency of the leu359 allele was 0.026 in Chinese-Taiwanese. They found that the leu359 allelic variant of CYP2C9 also has a lower affinity and a lower intrinsic clearance for S-warfarin 7-hydroxylation than the ile359 variant. Presumably, 7-hydroxylation has an important role in terminating the anticoagulant activity of warfarin in vitro, and individuals who are homozygous for the leu359 variant might require lower doses of this anticoagulant. In a patient who was unusually sensitive to warfarin therapy (see 122700), Steward et al. (1997) identified homozygosity for I359L, the so-called CYP2C9*3 allele. The patient, who was taking 0.5 mg of warfarin daily, had an S-to-R enantiomer ratio of 3.9:1, whereas control patients taking 4 to 8 mg of warfarin daily had S-to-R ratios of about 0.5:1. Steward et al. (1997) concluded that expression of CYP2C9*3 is associated with diminished clearance of the more potent S-warfarin, and that analysis of the plasma S-to-R warfarin ratio might serve as a useful alternative test to genotyping. Kidd et al. (1999) described a 29-year-old male Caucasian who had participated in 6 bioequivalence studies over a period of several years. The patient displayed severe hypoglycemia after a single dose of glipizide, a second generation sulfonylurea structurally similar to tolbutamide and used as an oral hypoglycemic agent. His oral clearance of phenytoin was 21% of the mean of 11 other individuals, and his oral clearance of glipizide was only 18% of the mean of 10 other individuals. His oral clearance of nifedipine (a CYP3A4 (124010) substrate) and chlorpheniramine (a CYP2D6 (see 124030) substrate) did not differ from that of other individuals studied. Genotype testing demonstrated that the individual was homozygous for the leu359 allele and did not possess any of the known defective CYP2C19 (124020) alleles. These studies established that the leu359 allele is responsible for the phenytoin and glipizide/tolbutamide poor metabolizer phenotype. In a study of 281 epileptic patients treated with phenytoin, Tate et al. (2005) found a significant association between the maximum dose needed and the CYP2C9*3 allele (I359L). Mean phenytoin doses for individuals with 0, 1, or 2 copies of the *3 allele were 354, 309, and 250 mg, respectively, indicating a trend of reduction in maximum dose needed to control symptoms. Ross et al. (2010) genotyped 963 individuals from 7 geographic regions for the CYP2C9*3 variant. The highest frequencies were observed in Europe (4 to 21%), the Middle East (3 to 11%) and Central/South Asia (5 to 15%). The allele was not observed in Africa or most populations from the Americas, except the Pima (7%). In Oceania, the allele was not present in Melanesians, but in Papua New Guinea the frequency was 12%. The allele was absent in many populations in East Asia, but reached frequencies of 10% or higher in some populations, such as the Tu, Tujia and Xibo. Similar frequencies were found in a Canadian cohort of 316 individuals of European, East Asian, and South Asian ancestry. (less)
|
|
drug response
(Jun 15, 2012)
|
no assertion criteria provided
Method: literature only
|
WARFARIN SENSITIVITY
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000029127.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Comment on evidence:
The ile359-to-leu (I359L) substitution results from a 1075A-C transversion in the CYP2C9 gene and is also known as rs1057910 and CYP2C9*3. The variant leads to … (more)
The ile359-to-leu (I359L) substitution results from a 1075A-C transversion in the CYP2C9 gene and is also known as rs1057910 and CYP2C9*3. The variant leads to reduced warfarin metabolism and increased risk of bleeding (Ross et al., 2010). Extensive interindividual variation in the response to a given dose Sullivan-Klose et al. (1996) demonstrated that the form of CYP2C9 in which ile359 is replaced by leucine is the basis of poor metabolizing of tolbutamide, the sulfonylurea hypoglycemic agent used in the treatment of diabetes mellitus (NIDDM; 125853). The frequency of the leu359 allele was found to be 0.06 in the Caucasian-American population and 0.005 in African Americans. The frequency of the leu359 allele was 0.026 in Chinese-Taiwanese. They found that the leu359 allelic variant of CYP2C9 also has a lower affinity and a lower intrinsic clearance for S-warfarin 7-hydroxylation than the ile359 variant. Presumably, 7-hydroxylation has an important role in terminating the anticoagulant activity of warfarin in vitro, and individuals who are homozygous for the leu359 variant might require lower doses of this anticoagulant. In a patient who was unusually sensitive to warfarin therapy (see 122700), Steward et al. (1997) identified homozygosity for I359L, the so-called CYP2C9*3 allele. The patient, who was taking 0.5 mg of warfarin daily, had an S-to-R enantiomer ratio of 3.9:1, whereas control patients taking 4 to 8 mg of warfarin daily had S-to-R ratios of about 0.5:1. Steward et al. (1997) concluded that expression of CYP2C9*3 is associated with diminished clearance of the more potent S-warfarin, and that analysis of the plasma S-to-R warfarin ratio might serve as a useful alternative test to genotyping. Kidd et al. (1999) described a 29-year-old male Caucasian who had participated in 6 bioequivalence studies over a period of several years. The patient displayed severe hypoglycemia after a single dose of glipizide, a second generation sulfonylurea structurally similar to tolbutamide and used as an oral hypoglycemic agent. His oral clearance of phenytoin was 21% of the mean of 11 other individuals, and his oral clearance of glipizide was only 18% of the mean of 10 other individuals. His oral clearance of nifedipine (a CYP3A4 (124010) substrate) and chlorpheniramine (a CYP2D6 (see 124030) substrate) did not differ from that of other individuals studied. Genotype testing demonstrated that the individual was homozygous for the leu359 allele and did not possess any of the known defective CYP2C19 (124020) alleles. These studies established that the leu359 allele is responsible for the phenytoin and glipizide/tolbutamide poor metabolizer phenotype. In a study of 281 epileptic patients treated with phenytoin, Tate et al. (2005) found a significant association between the maximum dose needed and the CYP2C9*3 allele (I359L). Mean phenytoin doses for individuals with 0, 1, or 2 copies of the *3 allele were 354, 309, and 250 mg, respectively, indicating a trend of reduction in maximum dose needed to control symptoms. Ross et al. (2010) genotyped 963 individuals from 7 geographic regions for the CYP2C9*3 variant. The highest frequencies were observed in Europe (4 to 21%), the Middle East (3 to 11%) and Central/South Asia (5 to 15%). The allele was not observed in Africa or most populations from the Americas, except the Pima (7%). In Oceania, the allele was not present in Melanesians, but in Papua New Guinea the frequency was 12%. The allele was absent in many populations in East Asia, but reached frequencies of 10% or higher in some populations, such as the Tu, Tujia and Xibo. Similar frequencies were found in a Canadian cohort of 316 individuals of European, East Asian, and South Asian ancestry. (less)
|
|
drug response
No CYP2C9 function
(Sep 24, 2020)
|
no assertion criteria provided
Method: case-control
|
Phenytoin response
Drug used for
status epilepticus
Affected status: yes
Allele origin:
germline
|
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne
Accession: SCV001441534.1
First in ClinVar: Nov 06, 2020 Last updated: Nov 06, 2020 |
Comment:
May cause toxicity/ADR and poor metabolism/PK
|
|
drug response
(Aug 31, 2010)
|
no assertion criteria provided
Method: research
|
Warfarin response
Drug used for
hemorrhage
Affected status: no
Allele origin:
unknown
|
Pharmacogenomics Lab, Chungbuk National University
Accession: SCV000889937.1
First in ClinVar: Sep 08, 2019 Last updated: Sep 08, 2019 |
Number of individuals with the variant: 12
|
|
drug response
likely responsive
(-)
|
no assertion criteria provided
Method: research
|
warfarin response
Drug used for
Venous thromboembolism
Affected status: yes
Allele origin:
germline
|
Faculty of Pharmacy, Damascus University
Accession: SCV005397927.1
First in ClinVar: Nov 17, 2024 Last updated: Nov 17, 2024 |
Comment:
rs1057910 is a SNP in the CYP2C9 gene and is linked to poor warfarin metabolism and risk of GI bleeding with warfarin, rs1057910 is associated … (more)
rs1057910 is a SNP in the CYP2C9 gene and is linked to poor warfarin metabolism and risk of GI bleeding with warfarin, rs1057910 is associated with reduced enzyme activity and lower clearance rates of warfarin leading to higher rates of warfarin concentration (less)
Sex: mixed
Geographic origin: Syria
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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 |
---|---|---|---|---|
Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C9 and HLA-B Genotypes and Phenytoin Dosing: 2020 Update. | Karnes JH | Clinical pharmacology and therapeutics | 2021 | PMID: 32779747 |
Efficacy of piroxicam for postoperative pain after lower third molar surgery associated with CYP2C8*3 and CYP2C9. | Calvo AM | Journal of pain research | 2017 | PMID: 28740425 |
CYP2C9 genotype vs. metabolic phenotype for individual drug dosing--a correlation analysis using flurbiprofen as probe drug. | Vogl S | PloS one | 2015 | PMID: 25775139 |
Effects of CYP2C9*1/*3 genotype on the pharmacokinetics of flurbiprofen in Korean subjects. | Lee YJ | Archives of pharmacal research | 2015 | PMID: 25712887 |
Clinical pharmacogenetics implementation consortium guidelines for CYP2C9 and HLA-B genotypes and phenytoin dosing. | Caudle KE | Clinical pharmacology and therapeutics | 2014 | PMID: 25099164 |
Worldwide allele frequency distribution of four polymorphisms associated with warfarin dose requirements. | Ross KA | Journal of human genetics | 2010 | PMID: 20555338 |
Genetically based impairment in CYP2C8- and CYP2C9-dependent NSAID metabolism as a risk factor for gastrointestinal bleeding: is a combination of pharmacogenomics and metabolomics required to improve personalized medicine? | Agúndez JA | Expert opinion on drug metabolism & toxicology | 2009 | PMID: 19422321 |
Genetic susceptibility to nonsteroidal anti-inflammatory drug-related gastroduodenal bleeding: role of cytochrome P450 2C9 polymorphisms. | Pilotto A | Gastroenterology | 2007 | PMID: 17681167 |
Impact of CYP2C9*3/*3 genotype on the pharmacokinetics and pharmacodynamics of piroxicam. | Perini JA | Clinical pharmacology and therapeutics | 2006 | PMID: 17112811 |
Influence of CYP2C9 genotypes on the pharmacokinetics and pharmacodynamics of piroxicam. | Perini JA | Clinical pharmacology and therapeutics | 2005 | PMID: 16198655 |
Genetic predictors of the maximum doses patients receive during clinical use of the anti-epileptic drugs carbamazepine and phenytoin. | Tate SK | Proceedings of the National Academy of Sciences of the United States of America | 2005 | PMID: 15805193 |
Differences in flurbiprofen pharmacokinetics between CYP2C9*1/*1, *1/*2, and *1/*3 genotypes. | Lee CR | European journal of clinical pharmacology | 2003 | PMID: 12698304 |
Pharmacokinetics of chlorpheniramine, phenytoin, glipizide and nifedipine in an individual homozygous for the CYP2C9*3 allele. | Kidd RS | Pharmacogenetics | 1999 | PMID: 10208645 |
Genetic association between sensitivity to warfarin and expression of CYP2C9*3. | Steward DJ | Pharmacogenetics | 1997 | PMID: 9352571 |
The role of the CYP2C9-Leu359 allelic variant in the tolbutamide polymorphism. | Sullivan-Klose TH | Pharmacogenetics | 1996 | PMID: 8873220 |
DailyMed Drug Label, FLURBIPROFEN, 2021 | - | - | - | - |
DailyMed Drug Label, ZURAMPIC, 2018 | - | - | - | - |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CYP2C9 | - | - | - | - |
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6039e036-c0aa-4249-af50-115f49ad758a | - | - | - | - |
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Text-mined citations for rs1057910 ...
HelpRecord 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.