ClinVar Miner

Submissions for variant NM_005957.4(MTHFR):c.1632+2T>G (rs749765738)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000167617 SCV000763907 pathogenic Homocysteinemia due to MTHFR deficiency 2018-11-09 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 and likely results in an absent or disrupted protein product. Loss-of-function variants in MTHFR are known to be pathogenic. This particular variant has been reported in the literature in an MTHFR-deficient individual (PMID: 25736335). This variant is also known as c.1644+2T>G in the literature. ClinVar contains an entry for this variant (Variation ID: 187897). Experimental studies have shown that this splice donor change leads to skipping of exon 10 (also known as exon 9) and significant reduction of MTHFR activity in vitro (PMID: 25736335). For these reasons, this variant has been classified as Pathogenic.
University Children's Hospital, University of Zurich RCV000167617 SCV000218498 pathogenic Homocysteinemia due to MTHFR deficiency no assertion criteria provided clinical testing

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