ClinVar Miner

Submissions for variant NM_005956.4(MTHFD1):c.983C>T (p.Pro328Leu)

gnomAD frequency: 0.00103  dbSNP: rs147367593
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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 RCV001921111 SCV002187930 uncertain significance not provided 2022-10-25 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 328 of the MTHFD1 protein (p.Pro328Leu). This variant is present in population databases (rs147367593, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with MTHFD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1415904). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MTHFD1 protein function. 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 RCV002503593 SCV002812848 uncertain significance Neural tube defects, folate-sensitive; Combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia 2021-09-15 criteria provided, single submitter clinical testing

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