NM_005957.5(MTHFR):c.1033C>T (p.Arg345Cys) AND Homocystinuria due to methylene tetrahydrofolate reductase deficiency

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Jul 22, 2021
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000416797.3

Allele description [Variation Report for NM_005957.5(MTHFR):c.1033C>T (p.Arg345Cys)]

NM_005957.5(MTHFR):c.1033C>T (p.Arg345Cys)

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.1033C>T (p.Arg345Cys)

HGVS:

NC_000001.11:g.11794862G>A
NG_013351.1:g.16242C>T
NM_001330358.2:c.1156C>T
NM_005957.5:c.1033C>TMANE SELECT
NP_001317287.1:p.Arg386Cys
NP_005948.3:p.Arg345Cys
NP_005948.3:p.Arg345Cys
LRG_726t1:c.1033C>T
LRG_726:g.16242C>T
LRG_726p1:p.Arg345Cys
NC_000001.10:g.11854919G>A
NM_005957.4:c.1033C>T

Protein change:

R345C

Links:

dbSNP: rs759031330

NCBI 1000 Genomes Browser:

rs759031330

Molecular consequence:

NM_001330358.2:c.1156C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_005957.5:c.1033C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Homocystinuria due to methylene tetrahydrofolate reductase deficiency
Synonyms:: HOMOCYSTINURIA DUE TO DEFICIENCY OF N(5,10)-METHYLENETETRAHYDROFOLATE REDUCTASE ACTIVITY; Homocysteinemia due to MTHFR deficiency; Homocysteinemia due to methylenetetrahydro-folate reductase deficiency; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009353; MedGen: C1856061; Orphanet: 395; OMIM: 236250

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000258405	University Children's Hospital, University of Zurich	criteria provided, single submitter (ZB-IEM Variant Assertion Criteria)	Pathogenic (Dec 3, 2004)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25736335, 26872964 ZB-IEM - Variant Assertion Criteria.docx, Citation Link,
SCV001810508	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jul 22, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000258405

University Children's Hospital, University of Zurich

criteria provided, single submitter

(ZB-IEM Variant Assertion Criteria)

Pathogenic
(Dec 3, 2004)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

ZB-IEM - Variant Assertion Criteria.docx,

Citation Link,

SCV001810508

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jul 22, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	1	not provided	not provided	not provided	clinical testing
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Insights into severe 5,10-methylenetetrahydrofolate reductase deficiency: molecular genetic and enzymatic characterization of 76 patients.

Burda P, Schäfer A, Suormala T, Rummel T, Bürer C, Heuberger D, Frapolli M, Giunta C, Sokolová J, Vlášková H, Kožich V, Koch HG, Fowler B, Froese DS, Baumgartner MR.

Hum Mutat. 2015 Jun;36(6):611-21. doi: 10.1002/humu.22779. Epub 2015 Apr 27.

PubMed [citation]

PMID:: 25736335

Mutation Update and Review of Severe Methylenetetrahydrofolate Reductase Deficiency.

Froese DS, Huemer M, Suormala T, Burda P, Coelho D, Guéant JL, Landolt MA, Kožich V, Fowler B, Baumgartner MR.

Hum Mutat. 2016 May;37(5):427-38. doi: 10.1002/humu.22970. Epub 2016 Mar 18.

PubMed [citation]

PMID:: 26872964

See all PubMed Citations (3)

Details of each submission

From University Children's Hospital, University of Zurich, SCV000258405.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (2)

Description

This variant was identified heterozygously in 1 patient in combination with c.1541_1542delAG (named from NM_005957.4).

#	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		1	not provided	1	not provided

From Genome-Nilou Lab, SCV001810508.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 23, 2024

ClinVar

Relating variation to medicine