ClinVar Miner

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

gnomAD frequency: 0.25830  dbSNP: rs1801131
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Total submissions: 23
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory of Genetics, Children's Clinical University Hospital Latvia RCV000430863 SCV006105658 benign not specified 2025-02-16 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System RCV005394111 SCV006054864 benign Homocystinuria due to methylene tetrahydrofolate reductase deficiency; Neural tube defects, folate-sensitive; Schizophrenia; Thrombophilia due to thrombin defect 2023-04-17 criteria provided, single submitter research
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre RCV001197542 SCV004805343 benign Homocystinuria due to methylene tetrahydrofolate reductase deficiency 2024-03-25 criteria provided, single submitter research
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000430863 SCV004099611 likely benign not specified 2023-09-07 criteria provided, single submitter clinical testing Variant summary: MTHFR c.1286A>C (p.Glu429Ala) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.29 in 251462 control chromosomes in the gnomAD database, including 11567 homozygotes strongly suggesting that the variant is benign. This variant, c.1286A>C is also known as 1298A>C. One publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in >50%-90% of normal activity and homocysteine levels for heterozygotes and homozygotes were not different from those with the wild type genotype, supporting the idea that this polymorphism alone might not significantly affect homocysteine metabolism (example: Weisberg_2001). The following publication has been ascertained in the context of this evaluation (PMID: 11395038). Ten submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as Benign/likely benign (n=7), uncertain significance (n=1), risk factor (n=1) and likely pathogenic (n=1). Based on the evidence outlined above, the variant was classified as likely benign.
Centre of Medical Genetics, University Hospital Muenster RCV001197542 SCV002506414 benign Homocystinuria due to methylene tetrahydrofolate reductase deficiency 2023-12-06 criteria provided, single submitter clinical testing ACMG categories: BA1, BP4
Genome-Nilou Lab RCV001197542 SCV001748535 benign Homocystinuria due to methylene tetrahydrofolate reductase deficiency 2021-07-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001197542 SCV001733272 benign Homocystinuria due to methylene tetrahydrofolate reductase deficiency 2026-02-04 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000153515 SCV001147148 benign not provided 2025-05-01 criteria provided, single submitter clinical testing MTHFR: BS1, BS2
Mendelics RCV000350590 SCV001135170 benign Neural tube defects, folate-sensitive 2019-05-28 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000153515 SCV000604289 benign not provided 2025-07-17 criteria provided, single submitter clinical testing
GeneDx RCV000153515 SCV000519507 benign not provided 2021-02-25 criteria provided, single submitter clinical testing 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)
Eurofins Ntd Llc (ga) RCV000153515 SCV000203039 other not provided 2017-01-13 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003974792 SCV004794374 benign MTHFR-related disorder 2023-12-01 no assertion criteria provided clinical testing This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000430863 SCV002037998 benign not specified no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000430863 SCV001956936 benign not specified no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000430863 SCV001928366 benign not specified no assertion criteria provided clinical testing
Clinical Genetics, Academic Medical Center RCV000430863 SCV001919429 benign not specified no assertion criteria provided clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000430863 SCV001741945 benign not specified no assertion criteria provided clinical testing
Natera, Inc. RCV001197542 SCV001455754 benign Homocystinuria due to methylene tetrahydrofolate reductase deficiency 2020-09-16 no assertion criteria provided clinical testing
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV001197542 SCV001368321 likely pathogenic Homocystinuria due to methylene tetrahydrofolate reductase deficiency 2019-01-28 flagged submission clinical testing This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: No criteria apply. This variant was detected in homozygous state.
Department of Pharmacy and Biotechnology, University of Bologna RCV000144922 SCV000187679 uncertain significance Gastrointestinal stromal tumor flagged submission case-control
OMIM RCV000003699 SCV000023862 risk factor Schizophrenia, susceptibility to 2008-07-01 no assertion criteria provided literature only
OMIM RCV000003698 SCV000023861 benign MTHFR THERMOLABILE POLYMORPHISM 2008-07-01 no assertion criteria provided literature only

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