ClinVar Miner

Submissions for variant NM_005957.5(MTHFR):c.1606G>T (p.Val536Phe)

dbSNP: rs786204028
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000167616 SCV003522741 uncertain significance Homocystinuria due to methylene tetrahydrofolate reductase deficiency 2022-03-29 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 536 of the MTHFR protein (p.Val536Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with MTHFR-related conditions (PMID: 25736335). ClinVar contains an entry for this variant (Variation ID: 187896). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Experimental studies have shown that this missense change affects MTHFR function (PMID: 27743313). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
University Children's Hospital, University of Zurich RCV000167616 SCV000218497 pathogenic Homocystinuria due to methylene tetrahydrofolate reductase deficiency no assertion criteria provided clinical testing

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