ClinVar Miner

Submissions for variant NM_001113378.1(FANCI):c.824T>C (p.Ile275Thr) (rs142906652)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000523947 SCV000616715 uncertain significance not provided 2017-07-07 criteria provided, single submitter clinical testing The I275T variant in the FANCI gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The I275T variant is observed in 64/66740 (0.095%) alleles from individuals of non-Finnish European background, in the ExAC dataset and no individuals were reported to be homozygous (Lek et al., 2016). The I275T 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 I275T as a variant of uncertain significance.
Invitae RCV000529696 SCV000626322 uncertain significance Fanconi anemia 2018-05-11 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 275 of the FANCI protein (p.Ile275Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is present in population databases (rs142906652, ExAC 0.1%). This variant has been reported in the literature in an individual with head and neck squamous cell carcinoma (PMID: 28678401). ClinVar contains an entry for this variant (Variation ID: 449021). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65". The threonine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.