ClinVar Miner

Submissions for variant NM_005957.5(MTHFR):c.1320G>A (p.Ser440=)

gnomAD frequency: 0.00004  dbSNP: rs367585605
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000167613 SCV002125525 pathogenic Homocystinuria due to methylene tetrahydrofolate reductase deficiency 2023-12-29 criteria provided, single submitter clinical testing This sequence change affects codon 440 of the MTHFR mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the MTHFR protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. This variant is present in population databases (rs367585605, gnomAD 0.004%). This variant has been observed in individual(s) with severe methylenetetrahydrofolate reductase deficiency (PMID: 25736335). This variant is also known as c.1332G>A. ClinVar contains an entry for this variant (Variation ID: 187893). Studies have shown that this variant results in activation of a cryptic donor splice site in intron 7 and introduces a premature termination codon (PMID: 25736335). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV002498831 SCV002809761 likely pathogenic Homocystinuria due to methylene tetrahydrofolate reductase deficiency; Neural tube defects, folate-sensitive; Schizophrenia; Thrombophilia due to thrombin defect 2021-08-10 criteria provided, single submitter clinical testing
Baylor Genetics RCV003462250 SCV004196405 pathogenic Neural tube defects, folate-sensitive 2024-02-08 criteria provided, single submitter clinical testing
University Children's Hospital, University of Zurich RCV000167613 SCV000218494 pathogenic Homocystinuria due to methylene tetrahydrofolate reductase deficiency no assertion criteria provided clinical testing

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