NM_005957.5(MTHFR):c.665C>T (p.Ala222Val) AND methotrexate response - Toxicity - ClinVar

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NM_005957.5(MTHFR):c.665C>T (p.Ala222Val) AND methotrexate response - Toxicity

Germline classification:: drug response (1 submission)
Last evaluated:: Mar 24, 2021
Review status:: 3 stars out of maximum of 4 stars
reviewed by expert panel

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001847567.2

Allele description

NM_005957.5(MTHFR):c.665C>T (p.Ala222Val)

Gene:

MTHFR:methylenetetrahydrofolate reductase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.22

Genomic location:

Preferred name:

NM_005957.5(MTHFR):c.665C>T (p.Ala222Val)

Other names:

MTHFR, 677C-T, ALA222VAL (rs1801133); C667T

HGVS:

NC_000001.11:g.11796321G>A
NG_013351.1:g.14783C>T
NM_001330358.2:c.788C>T
NM_005957.5:c.665C>TMANE SELECT
NP_001317287.1:p.Ala263Val
NP_005948.3:p.Ala222Val
NP_005948.3:p.Ala222Val
LRG_726t1:c.665C>T
LRG_726:g.14783C>T
LRG_726p1:p.Ala222Val
NC_000001.10:g.11856378G>A
NM_005957.4:c.665C>T
P42898:p.Ala222Val

Protein change:

A222V; ALA222VAL

Links:

Genetic Testing Registry (GTR): GTR000593372; PharmGKB: 827848365; PharmGKB: 827848365PA450428; PharmGKB: 981204929; PharmGKB: 981204929PA449165; PharmGKB: 981220481; PharmGKB: 981220481PA448803; PharmGKB Clinical Annotation: 981204929; PharmGKB Clinical Annotation: 981220481; UniProtKB: P42898#VAR_009528; OMIM: 607093.0003; dbSNP: rs1801133

NCBI 1000 Genomes Browser:

rs1801133

Molecular consequence:

NM_001330358.2:c.788C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_005957.5:c.665C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: methotrexate response - Toxicity
Synonyms:: Methotrexate poisoning; Methotrexate toxicity
Identifiers:: MONDO: MONDO:0034212; MedGen: C0568062

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002031239	PharmGKB	reviewed by expert panel (Pharmacogenomics knowledge for personalized medicine)	drug response (Mar 24, 2021) Condition: methotrexate response - Toxicity Drug reported used for: Arthritis, Juvenile Rheumatoid	germline	curation	PubMed (42) [See all records that cite these PMIDs] 11418485, 11710708, 12453860, 12915598, 16501586, 16870553, 17488658, 17512587, 18381794, 18458567, 19031955, 19648163, 20472929, 20514079, 20595278, 20863444, 21534867, 21644011, 21931346, 22074251, 22143415, 23089671, 23095111, 23488607, 23648444, 24241962, 25007187, 25110820, 25177243, 25778468, 27104192, 27217051, 27399166, 27781293, 27992285, 28696419, 29589488, 29911750, 30684021, 32612964, 32695297, 22992668 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002031239

PharmGKB

reviewed by expert panel

(Pharmacogenomics knowledge for personalized medicine)

drug response
(Mar 24, 2021)
Condition: methotrexate response - Toxicity
Drug reported used for: Arthritis, Juvenile Rheumatoid

germline

curation

PubMed (42)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	curation

Citations

PubMed

Pharmacogenetics of methotrexate: toxicity among marrow transplantation patients varies with the methylenetetrahydrofolate reductase C677T polymorphism.

Ulrich CM, Yasui Y, Storb R, Schubert MM, Wagner JL, Bigler J, Ariail KS, Keener CL, Li S, Liu H, Farin FM, Potter JD.

Blood. 2001 Jul 1;98(1):231-4.

PubMed [citation]

PMID:: 11418485

The C677T mutation in the methylenetetrahydrofolate reductase gene: a genetic risk factor for methotrexate-related elevation of liver enzymes in rheumatoid arthritis patients.

van Ede AE, Laan RF, Blom HJ, Huizinga TW, Haagsma CJ, Giesendorf BA, de Boo TM, van de Putte LB.

Arthritis Rheum. 2001 Nov;44(11):2525-30.

PubMed [citation]

PMID:: 11710708

See all PubMed Citations (42)

Details of each submission

From PharmGKB, SCV002031239.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (42)

Description

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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Aug 26, 2023

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