ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.659T>G (p.Phe220Cys)

dbSNP: rs1012529150
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001227674 SCV001400042 uncertain significance Fanconi anemia 2019-08-20 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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 C15". The cysteine 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. This variant has not been reported in the literature in individuals with FANCC-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with cysteine at codon 220 of the FANCC protein (p.Phe220Cys). The phenylalanine residue is moderately conserved and there is a large physicochemical difference between phenylalanine and cysteine.
Ambry Genetics RCV002366021 SCV002662698 uncertain significance Hereditary cancer-predisposing syndrome 2024-02-29 criteria provided, single submitter clinical testing The p.F220C variant (also known as c.659T>G), located in coding exon 6 of the FANCC gene, results from a T to G substitution at nucleotide position 659. The phenylalanine at codon 220 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001227674 SCV002081235 uncertain significance Fanconi anemia 2020-07-15 no assertion criteria provided clinical testing

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.