Submissions for variant NM_001113378.2(FANCI):c.1412C>G (p.Pro471Arg)

gnomAD frequency: 0.00007  dbSNP: rs139072231

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000466858	SCV000547825	uncertain significance	Fanconi anemia	2022-09-13	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 471 of the FANCI protein (p.Pro471Arg). This variant is present in population databases (rs139072231, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with FANCI-related conditions. ClinVar contains an entry for this variant (Variation ID: 408243). 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 expected to disrupt FANCI 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.
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.
Fulgent Genetics, Fulgent Genetics	RCV000763988	SCV000894939	uncertain significance	Fanconi anemia complementation group I	2022-02-12	criteria provided, single submitter	clinical testing
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV000658083	SCV002011151	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing