ClinVar Miner

Submissions for variant NM_005957.5(MTHFR):c.665C>T (p.Ala222Val) (rs1801133)

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Total submissions: 15
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PharmGKB RCV000211133 SCV000268236 drug response cyclophosphamide response - Toxicity/ADR 2016-07-11 reviewed by expert panel curation PharmGKB Level of Evidence 2A: Annotation for a variant-drug combination that qualifies for level 2B where the variant is within a VIP (Very Important Pharmacogene) as defined by PharmGKB. The variants in level 2A are in known pharmacogenes, so functional significance is more likely.
PharmGKB RCV000211336 SCV000268238 drug response carboplatin response - Efficacy 2016-07-11 reviewed by expert panel curation PharmGKB Level of Evidence 2A: Annotation for a variant-drug combination that qualifies for level 2B where the variant is within a VIP (Very Important Pharmacogene) as defined by PharmGKB. The variants in level 2A are in known pharmacogenes, so functional significance is more likely.
PharmGKB RCV000417131 SCV000494694 drug response methotrexate response - Dosage, Efficacy, Toxicity/ADR 2018-05-14 reviewed by expert panel curation PharmGKB Level of Evidence 2A: Annotation for a variant-drug combination that qualifies for level 2B where the variant is within a VIP (Very Important Pharmacogene) as defined by PharmGKB. The variants in level 2A are in known pharmacogenes, so functional significance is more likely.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000153516 SCV000203040 other not provided 2017-01-13 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000259890 SCV000347807 likely benign Neural tube defects, folate-sensitive 2016-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000428048 SCV000519504 benign not specified 2016-04-25 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000428048 SCV000884146 uncertain significance not specified 2018-07-13 criteria provided, single submitter clinical testing
Mendelics RCV000259890 SCV001135171 likely benign Neural tube defects, folate-sensitive 2019-05-28 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000153516 SCV001147149 uncertain significance not provided 2016-10-01 criteria provided, single submitter clinical testing
Myriad Women's Health, Inc. RCV001030751 SCV001194043 pathogenic Homocystinuria due to methylene tetrahydrofolate reductase deficiency 2019-12-16 criteria provided, single submitter clinical testing NM_005957.4(MTHFR):c.665C>T(A222V) is a common variant present in approximately 30% of the general population. While many individuals who are homozygous for this variant are asymptomatic, some may have mild MTHFR deficiency associated with increased plasma homocysteine. Sources cited for classification include the following: PMID 7647779, 8837319, 9545406, 11781870, 12560871, 8903338, 9789068, 11929966, 15565101, 17436239, 12356947, 9133512, 12196644 and 9798595. Classification of NM_005957.4(MTHFR):c.665C>T(A222V) is based on the following criteria: This is a well-established variant in the literature that has been observed more frequently in patients with mild MTHFR deficiency than in healthy populations and there is functional data showing deficient protein function. Please note: this variant was assessed in the context of healthy population screening.
OMIM RCV000003697 SCV000023860 benign MTHFR deficiency, thermolabile type 2019-06-11 no assertion criteria provided literature only
FirmaLab RCV000003697 SCV000106043 pathogenic MTHFR deficiency, thermolabile type no assertion criteria provided clinical testing
Department of Pharmacy and Biotechnology,University of Bologna RCV000144921 SCV000187678 uncertain significance Gastrointestinal stromal tumor no assertion criteria provided case-control
Database of Curated Mutations (DoCM) RCV000427078 SCV000505736 not provided Neoplasm of stomach 2016-03-10 no assertion provided literature only
Department of Genetics,Sultan Qaboos University Hospital, Oman RCV000761447 SCV000891532 uncertain significance Venous thrombosis 2017-12-30 no assertion criteria provided curation

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