ClinVar Miner

Submissions for variant NM_005957.5(MTHFR):c.1408G>T (p.Glu470Ter)

dbSNP: rs139645527
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000791536 SCV000930791 pathogenic Homocystinuria due to methylene tetrahydrofolate reductase deficiency 2024-01-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu470*) in the MTHFR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MTHFR are known to be pathogenic (PMID: 25736335). This variant is present in population databases (no rsID available, gnomAD 0.003%). This premature translational stop signal has been observed in individuals with methylenetetrahydrofolate reductase deficiency (PMID: 25736335). ClinVar contains an entry for this variant (Variation ID: 638867). For these reasons, this variant has been classified as Pathogenic.
Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences RCV000791536 SCV001451948 pathogenic Homocystinuria due to methylene tetrahydrofolate reductase deficiency criteria provided, single submitter research
3billion RCV000791536 SCV003841510 pathogenic Homocystinuria due to methylene tetrahydrofolate reductase deficiency 2023-02-23 criteria provided, single submitter clinical testing The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: <0.001%). This variant was predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000638867). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.
Baylor Genetics RCV003461066 SCV004196387 pathogenic Neural tube defects, folate-sensitive 2024-01-25 criteria provided, single submitter clinical testing
Natera, Inc. RCV000791536 SCV002094629 pathogenic Homocystinuria due to methylene tetrahydrofolate reductase deficiency 2021-05-05 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.