NM_005957.5(MTHFR):c.1286A>C (p.Glu429Ala) AND not provided

Germline classification:: Benign; other (4 submissions)
Last evaluated:: Nov 29, 2023
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:: RCV000153515.39

Allele description [Variation Report for NM_005957.5(MTHFR):c.1286A>C (p.Glu429Ala)]

NM_005957.5(MTHFR):c.1286A>C (p.Glu429Ala)

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.1286A>C (p.Glu429Ala)

Other names:

MTHFR, 1298A-C, GLU429ALA (rs1801131); E429A

HGVS:

NC_000001.11:g.11794419T>G
NG_013351.1:g.16685A>C
NM_001330358.2:c.1409A>C
NM_005957.5:c.1286A>CMANE SELECT
NP_001317287.1:p.Glu470Ala
NP_005948.3:p.Glu429Ala
NP_005948.3:p.Glu429Ala
LRG_726t1:c.1286A>C
LRG_726:g.16685A>C
LRG_726p1:p.Glu429Ala
NC_000001.10:g.11854476T>G
NM_005957.4:c.1286A>C
P42898:p.Glu429Ala

Protein change:

E470A; GLU429ALA

Links:

Genetic Testing Registry (GTR): GTR000593372; PharmGKB Clinical Annotation: 1183705832; UniProtKB: P42898#VAR_014882; OMIM: 607093.0004; dbSNP: rs1801131

NCBI 1000 Genomes Browser:

rs1801131

Molecular consequence:

NM_001330358.2:c.1409A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_005957.5:c.1286A>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

173

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000203039	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	other (Jan 13, 2017)	germline	clinical testing	Citation Link,
SCV000519507	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Benign (Feb 25, 2021)	germline	clinical testing	Citation Link,
SCV000604289	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024)	Benign (Nov 29, 2023)	germline	clinical testing	Citation Link,
SCV001147148	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Benign (Jul 1, 2023)	germline	clinical testing	Citation Link

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	4	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	169	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From Eurofins Ntd Llc (ga), SCV000203039.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	169	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		169	not provided	not provided	not provided

From GeneDx, SCV000519507.4

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

Description

E429A, commonly reported as c.1298A>C, is a benign variant. It results in reduced MTHFR activity but it is not associated with increased plasma folate concentration in the heterozygous or homozygous state. This variant is present in 31% of alleles in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 9545395, 18842806, 21241403, 22882325, 18836720, 21577095, 20135343, 23652803, 18992148, 23162020, 23771968, 19936946, 19837268, 20031554, 19232336, 19356065, 11875032, 22102315, 21897766, 21334398, 21845428, 20935396, 20532637, 21080081, 18583979, 21613384, 19854238, 21107737, 11395038, 9719624, 26238013, 27068821, 27330833, 23659764, 24109560, 23685927, 11274424, 29600437, 24440586, 22051736, 29395581, 20078877, 24175756, 24488901, 24301776, 22576927, 25573130, 29974397, 26135458, 23523621, 16489479)

#	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

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV000604289.8

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

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

From CeGaT Center for Human Genetics Tuebingen, SCV001147148.21

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	4	not provided	not provided	clinical testing	not provided

Description

MTHFR: BP4, BS1, BS2

#	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		4	not provided	not provided	not provided

Last Updated: Jun 23, 2024

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