ClinVar Miner

Submissions for variant NM_005957.5(MTHFR):c.1632+2T>G

gnomAD frequency: 0.00001  dbSNP: rs749765738
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000167617 SCV000763907 pathogenic Homocystinuria due to methylene tetrahydrofolate reductase deficiency 2023-10-27 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 10 of the MTHFR gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MTHFR are known to be pathogenic (PMID: 25736335). This variant is present in population databases (rs749765738, gnomAD 0.007%). Disruption of this splice site has been observed in individual(s) with MTHFR deficiency (PMID: 25736335). This variant is also known as c.1644+2T>G. ClinVar contains an entry for this variant (Variation ID: 187897). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001753577 SCV001987710 likely pathogenic not provided 2021-10-14 criteria provided, single submitter clinical testing Canonical splice site variant predicted to result in an in-frame deletion of a critical region; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 29246599, 26872964, 25736335)
Fulgent Genetics, Fulgent Genetics RCV002492678 SCV002786101 pathogenic Homocystinuria due to methylene tetrahydrofolate reductase deficiency; Neural tube defects, folate-sensitive; Schizophrenia; Thrombophilia due to thrombin defect 2022-05-02 criteria provided, single submitter clinical testing
Baylor Genetics RCV003468815 SCV004196465 pathogenic Neural tube defects, folate-sensitive 2022-02-15 criteria provided, single submitter clinical testing
University Children's Hospital, University of Zurich RCV000167617 SCV000218498 pathogenic Homocystinuria due to methylene tetrahydrofolate reductase deficiency no assertion criteria provided clinical testing
Natera, Inc. RCV000167617 SCV001455751 pathogenic Homocystinuria due to methylene tetrahydrofolate reductase deficiency 2020-09-16 no assertion criteria provided clinical testing

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