{{Rsnum
|rsid=4986893
|Gene=CYP2C19
|Chromosome=10
|position=94780653
|Orientation=plus
|ReferenceAllele=G
|GMAF=0.01423
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|Summary=Clopidogrel (Plavix®)
|geno1=(A;A)
|geno2=(A;G)
|geno3=(G;G)
|Gene_s=CYP2C19
}}{{CPMC SNP
|link=https://cpmc.coriell.org/Sections/Results/Plavix.aspx?PgId=212
}}
[[rs4986893]] is a SNP in the [[CYP2C19]] gene, potentially encoding the CYP2C19*3 variant. This variant has been linked to poor metabolism of compounds like mephenytoin as well as [[proguanil]], and it therefore has implications for [[malaria]] prophylaxis. [PMID 7969038, PMID 9093256]

The risk allele is [[rs4986893]](A).

As a nonfunctioning [[CYP2C19]], this variant would be expected to be a poor metabolizer of several commonly prescribed drugs, including anti-[[ulcer]] drugs like [[omeprazole]] (trade names [[Losec]] and [[Prilosec]]), [[esomeprazole]] (trade name [[Nexium]]), and [[lansoprazole]] ([[Prevacid]]).

{{omim
|desc=MEPHENYTOIN, POOR METABOLISM OF
|id=124020
|quiet=1
|rsnum=4986893
|variant=0003
}}

{{PharmGKB
|RSID=rs4986893
|Name_s=CYP2C19*3
|Gene_s=CYP2C19
|Feature=Exon/NonSyn
|Evidence=PubMed ID:16338278
|Annotation=In contrast to other PPIs, esomeprazole-induced healing of GERD appears to be unrelated to the CYP2C19*3 variant.
|Drugs=esomeprazole
|Drug Classes=
|Diseases=Gastroesophageal Reflux
|Curation Level=Curated
|PharmGKB Accession ID=PA162652697
}}

{{PharmGKB
|RSID=rs4986893
|Name_s=CYP2C19:636G>A
|Gene_s=CYP2C19
|Feature=Exon/NonSyn
|Evidence=Web Resource:http://www.pharmgkb.org/search/annotatedGene/cyp2c19/haplotype.jsp#ImportantHaplotypeInformationforCYP2C19-3; Web Resource:http://www.pharmgkb.org/search/annotatedGene/cyp2c19/variant.jsp#ImportantVariantInformationforCYP2C19-636
|Annotation=This variant results in a premature termination codon in cDNA; defining variant for CYP2C19*3.
|Drugs=
|Drug Classes=
|Diseases=
|Curation Level=In-Depth
|PharmGKB Accession ID=PA161145196
}}

{{PharmGKB
|RSID=rs4986893
|Name_s=CYP2C19*3, CYP2C19:G636A
|Gene_s=CYP2C19
|Feature=Exon/NonSyn
|Evidence=PubMed ID:19106083
|Annotation=Subjects who had previously experienced myocardial infarction and were receiving clopidogrel were almost twice as likely to experience a subsequent cardiovascular event if they carried any two CYP2C19 loss-of-function alleles (CYP2C19*2, CYP2C19*3, CYP2C19*4 or CYP2C19*5) relative to those with none. Patients from this study who underwent percutaneous coronary intervention and carried two CYP2C19 loss-of-function alleles had a 3.58 times greater risk of cardiovascular events as those with none. These results suggest that treatment with clopidogrel is less effective in individuals who are homozygous for CYP2C19 loss-of-function alleles than in those who do not carry CYP2C19 loss-of-function alleles.
|Drugs=clopidogrel
|Drug Classes=
|Diseases=Cardiovascular Diseases; Death; Myocardial Infarction; Stroke
|Curation Level=Curated
|PharmGKB Accession ID=PA162363761
}}
{{PMID Auto
|PMID=21247447
|Title=CYP2C19 and ABCB1 gene polymorphisms are differently distributed according to ethnicity in the Brazilian general population
|OA=1
}}

{{ClinVar
|rsid=4986893
|Reversed=0
|FwdREF=G
|FwdALT=A
|REF=G
|ALT=A
|RSPOS=96540410
|CHROM=10
|GMAF=0.0142
|dbSNPBuildID=113
|SSR=0
|SAO=1
|VP=0x050378000000150516110101
|GENEINFO=CYP2C19:1557
|GENE_NAME=CYP2C19
|GENE_ID=1557
|WGT=0
|VC=SNV
|CLNALLE=1
|CLNHGVS=NC_000010.10:g.96540410G>A
|CLNORIGIN=1
|CLNSIG=6
|Tags=PM;TPA;PMC;S3D;SLO;VLD;G5;HD;GNO;KGPhase1;KGPROD;OTHERKG;LSD;OM
|CAF=0.9858; 0.01423
|CLNACC=RCV000018397.26; RCV000018398.26
|CLNDBN=Mephenytoin, poor metabolism of; Proguanil, poor metabolism of
|CLNDSDB=MedGen
|CLNDSDBID=C1836024; C1836026
|CLNSRC=OMIM Allelic Variant
|CLNSRCID=124020.0003
|COMMON=1
|Disease=Mephenytoin; Proguanil
}}

{{PMID Auto
|PMID=18521743
|Title=CYP2C19*17 is associated with decreased breast cancer risk.
}}

{{PMID Auto
|PMID=18547414
|Title=Genotyping panel for assessing response to cancer chemotherapy.
|OA=1
}}

{{PMID Auto
|PMID=18936436
|Title=Prevalence in the United States of selected candidate gene variants: Third National Health and Nutrition Examination Survey, 1991-1994.
|OA=1
}}

{{PMID Auto
|PMID=18974781
|Title=Cataloging coding sequence variations in human genome databases.
|OA=1
}}

{{PMID Auto
|PMID=19136640
|Title=Rapid identification of the hepatic cytochrome P450 2C19 activity using a novel and noninvasive [13C]pantoprazole breath test.
|OA=1
}}

{{PMID Auto
|PMID=21071160
|Title=Analysis of 50 SNPs in CYP2D6, CYP2C19, CYP2C9, CYP3A4 and CYP1A2 by MALDI-TOF mass spectrometry in Chinese Han population.
}}

{{PMID Auto
|PMID=22265638
|Title=The impact of genetic polymorphisms of P2Y12, CYP3A5 and CYP2C19 on clopidogrel response variability in Iranian patients.
}}

{{GET Evidence
|gene=CYP2C19
|aa_change=Trp212Stop
|aa_change_short=W212X
|impact=pharmacogenetic
|qualified_impact=Insufficiently evaluated pharmacogenetic
|inheritance=recessive
|quality_scores=Array
|dbsnp_id=rs4986893
|overall_frequency_n=1
|overall_frequency_d=128
|overall_frequency=0.0078125
|n_genomes=1
|n_genomes_annotated=0
|n_haplomes=1
|n_articles=7
|n_articles_annotated=7
|qualityscore_in_silico=3
|qualitycomment_in_silico=Y
|qualityscore_case_control=4
|qualitycomment_case_control=Y
|qualityscore_severity=4
|qualitycomment_severity=Y
|qualityscore_treatability=4
|qualitycomment_treatability=Y
|in_omim=Y
|in_pharmgkb=Y
|nblosum100=10
|autoscore=4
|webscore=N
|n_web_uneval=10
|summary_short=CYP2C19*3 allele. Poor metabolism of Mephenytoin, poor metabolism of Proguanil (FDA approved).
}}

[[Clopidogrel Efficacy]]

{{PMID Auto
|PMID=23517020
|Title=Influence of CYP2C19*2 and *3 loss-of-function alleles on pharmacodynamic effects of standard- and high-dose clopidogrel in East Asians undergoing percutaneous coronary intervention: the results of the ACCEL-DOUBLE-2N3 study
}}

{{PMID Auto
|PMID=23661171
|Title=CYP2C19 genotypes and their impact on clopidogrel responsiveness in percutaneous coronary intervention
}}

{{PMID Auto
|PMID=23645039
|Title=High prevalence of CYP2C19*2 allele in Roma samples: study on Roma and Hungarian population samples with review of the literature
}}

{{PMID Auto
|PMID=23130019
|Title=Frequencies of 23 functionally significant variant alleles related with metabolism of antineoplastic drugs in the chilean population: comparison with caucasian and asian populations.
|OA=1
}}

{{PMID Auto
|PMID=23133420
|Title=Pharmacogenomic Diversity among Brazilians: Influence of Ancestry, Self-Reported Color, and Geographical Origin.
|OA=1
}}

{{on chip | 23andMe v1}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | FTDNA2}}
{{on chip | FTDNA}}
{{on chip | HumanOmni1Quad}}