ClinVar Miner

Submissions for variant NM_052859.4(RFT1):c.1324C>T (p.Arg442Trp)

gnomAD frequency: 0.00003  dbSNP: rs146610276
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000437676 SCV000535105 uncertain significance not provided 2016-12-20 criteria provided, single submitter clinical testing The R442W variant in the RFT1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R442W variant was not observed at any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R442W variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret R442W as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001861633 SCV002168779 uncertain significance RFT1-congenital disorder of glycosylation 2022-03-22 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 442 of the RFT1 protein (p.Arg442Trp). This variant is present in population databases (rs146610276, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with RFT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 391934). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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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