ClinVar Miner

Submissions for variant NM_005956.4(MTHFD1):c.1390A>G (p.Ile464Val)

gnomAD frequency: 0.00019  dbSNP: rs139264994
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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 RCV001362072 SCV001558072 uncertain significance not provided 2022-09-13 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 464 of the MTHFD1 protein (p.Ile464Val). This variant is present in population databases (rs139264994, gnomAD 0.03%). 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: 1053697). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 RCV002488104 SCV002801517 uncertain significance Neural tube defects, folate-sensitive; Combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia 2022-04-13 criteria provided, single submitter clinical testing

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