ClinVar Miner

Submissions for variant NM_005957.5(MTHFR):c.1537T>A (p.Leu513Ile)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Neuberg Centre For Genomic Medicine, NCGM RCV004785813 SCV005400867 uncertain significance Thrombophilia due to thrombin defect 2023-06-22 criteria provided, single submitter clinical testing The observed missense c.1537T>A(p.Leu513Ile) variant in MTHFR gene has not been reported previously as a pathogenic variant nor a benign variant, to our knowledge. The p.Leu513Ile variant has been reported with allele frequency of 0.0008% in gnomAD Exomes. This variant has not been submitted to the ClinVar database. Multiple lines of computational evidences (Polyphen - Benign, SIFT - Tolerated and MutationTaster - Disease causing) predict conflicting evidence on protein structure and function for this variant. The reference amino acid change at this position on MTHFR gene is predicted as conserved by PhyloP across 100 vertebrates. The amino acid Leu at position 513 is changed to a Ile changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as a Variant of Uncertain Significance (VUS).

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