ClinVar Miner

Submissions for variant NM_001113378.1(FANCI):c.1412C>G (p.Pro471Arg) (rs139072231)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics,Fulgent Genetics RCV000763988 SCV000894939 uncertain significance Fanconi anemia, complementation group I 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000658083 SCV000779854 uncertain significance not provided 2018-05-18 criteria provided, single submitter clinical testing The P471R variant in the FANCI gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The P471R variant is observed in 15/126,596 (0.01%) alleles from individuals of non-Finnish European background in large population cohorts (Lek et al., 2016). The P471R 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. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. We interpret P471R as a variant of uncertain significance.
Invitae RCV000466858 SCV000547825 uncertain significance Fanconi anemia 2018-06-06 criteria provided, single submitter clinical testing This sequence change replaces proline with arginine at codon 471 of the FANCI protein (p.Pro471Arg). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and arginine. This variant is present in population databases (rs139072231, ExAC 0.01%). This variant has not been reported in the literature in individuals with FANCI-related disease. ClinVar contains an entry for this variant (Variation ID: 408243). 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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