ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.1561G>A (p.Glu521Lys) (rs752855423)

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 RCV000215546 SCV000279409 uncertain significance not provided 2019-01-07 criteria provided, single submitter clinical testing This variant is denoted FANCC c.1561G>A at the cDNA level, p.Glu521Lys (E521K) at the protein level, and results in the change of a Glutamic Acid to a Lysine (GAG>AAG). FANCC Glu521Lys has been reported in a pancreatic adenocarcinoma cell line, but it is unknown if the variant was somatic or germline (van der Heijden 2003). FANCC Glu521Lys was not observed at a significant allele frequency in large population cohorts (Lek 2016). FANCC Glu521Lys is located in the cdc2 binding region (Gordon and Buchwald 2000). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether FANCC Glu521Lys is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000706885 SCV000835959 uncertain significance Fanconi anemia 2018-11-01 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 521 of the FANCC protein (p.Glu521Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs752855423, ExAC 0.002%). This variant has not been reported in the literature in individuals with FANCC-related disease. ClinVar contains an entry for this variant (Variation ID: 234512). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.