ClinVar Miner

Submissions for variant NM_005956.4(MTHFD1):c.1913C>T (p.Pro638Leu)

gnomAD frequency: 0.00006  dbSNP: rs149492308
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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 RCV001957522 SCV002206407 uncertain significance not provided 2021-09-02 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 638 of the MTHFD1 protein (p.Pro638Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs149492308, ExAC 0.02%). This variant has not been reported in the literature in individuals affected with MTHFD1-related conditions. 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"). 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.
Fulgent Genetics, Fulgent Genetics RCV002484589 SCV002792621 uncertain significance Neural tube defects, folate-sensitive; Combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia 2021-09-21 criteria provided, single submitter clinical testing

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