Submissions for variant NM_024006.4(VKORC1):c.-1639G>A

gnomAD frequency: 0.31727  dbSNP: rs9923231

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PharmGKB	RCV001787364	SCV002031257	drug response	phenprocoumon response - Dosage	2021-03-24	reviewed by expert panel	curation	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.
PharmGKB	RCV001787365	SCV002031258	drug response	phenprocoumon response - Toxicity	2021-03-24	reviewed by expert panel	curation	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.
PharmGKB	RCV001787366	SCV002031259	drug response	warfarin response - Toxicity	2021-03-24	reviewed by expert panel	curation	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.
PharmGKB	RCV003227594	SCV003925522	drug response	acenocoumarol response - Dosage	2021-03-24	reviewed by expert panel	curation	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.
PharmGKB	RCV003227593	SCV003925523	drug response	warfarin response - Dosage	2021-11-19	reviewed by expert panel	curation	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.
PharmGKB	RCV003227595	SCV003925524	drug response	warfarin response - Efficacy	2021-03-24	reviewed by expert panel	curation	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.
Eurofins Ntd Llc (ga)	RCV000377657	SCV000331715	other	not provided	2018-08-08	criteria provided, single submitter	clinical testing
GeneDx	RCV000603173	SCV000724152	likely benign	not specified	2018-03-09	criteria provided, single submitter	clinical testing	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000377657	SCV005838942	benign	not provided	2024-03-25	criteria provided, single submitter	clinical testing
OMIM	RCV000002295	SCV000022453	pathogenic	Warfarin response	2010-09-01	no assertion criteria provided	literature only
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000002295	SCV000202013	drug response	Warfarin response	2006-12-16	no assertion criteria provided	clinical testing
Faculty of Pharmacy, Damascus University	RCV003150805	SCV003836537	protective	Venous thromboembolism		no assertion criteria provided	research	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).
PreventionGenetics, part of Exact Sciences	RCV003952337	SCV004778777	likely benign	VKORC1-related disorder	2021-07-20	no assertion criteria provided	clinical testing	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).
Department of Pharmacology - Sarajevo Medical School, University Sarajevo School of Science and Technology	RCV003996074	SCV004807478	uncertain significance	Thrombus		no assertion criteria provided	research
Department of Pharmacology - Sarajevo Medical School, University Sarajevo School of Science and Technology	RCV003993732	SCV004812937	uncertain significance	See cases		no assertion criteria provided	case-control	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