ClinVar Miner

Submissions for variant NM_005957.5(MTHFR):c.3G>C (p.Met1Ile)

gnomAD frequency: 0.00021  dbSNP: rs373076763
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000594799 SCV000707497 uncertain significance not provided 2017-04-25 criteria provided, single submitter clinical testing
New York Genome Center RCV002265818 SCV002548722 uncertain significance Homocystinuria due to methylene tetrahydrofolate reductase deficiency 2021-08-13 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002265818 SCV003267645 pathogenic Homocystinuria due to methylene tetrahydrofolate reductase deficiency 2024-01-21 criteria provided, single submitter clinical testing This sequence change affects the initiator methionine of the MTHFR mRNA. The next in-frame methionine is located at codon 49. This variant is present in population databases (rs373076763, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with MTHFR-related conditions. ClinVar contains an entry for this variant (Variation ID: 501216). This variant disrupts a region of the MTHFR protein in which other variant(s) (p.Arg46Gln) have been determined to be pathogenic (PMID: 25736335, 28241805). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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