ClinVar Miner

Submissions for variant NM_005957.5(MTHFR):c.907G>A (p.Val303Met)

gnomAD frequency: 0.00010  dbSNP: rs143466425
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001763197 SCV001991808 uncertain significance not provided 2019-08-02 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV002540322 SCV003440478 uncertain significance Homocystinuria due to methylene tetrahydrofolate reductase deficiency 2022-03-01 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 303 of the MTHFR protein (p.Val303Met). This variant is present in population databases (rs143466425, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with MTHFR-related conditions. ClinVar contains an entry for this variant (Variation ID: 1307661). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.

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