ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.990C>G (p.Ser330Arg) (rs374915316)

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 RCV000481385 SCV000571782 uncertain significance not provided 2018-04-27 criteria provided, single submitter clinical testing This variant is denoted FANCC c.990C>G at the cDNA level, p.Ser330Arg (S330R) at the protein level, and results in the change of a Serine to an Arginine (AGC>AGG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. FANCC Ser330Arg was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the Hsp70 binding domain (Gordon & 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 Ser330Arg is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000630962 SCV000751938 uncertain significance Fanconi anemia 2017-10-03 criteria provided, single submitter clinical testing This sequence change replaces serine with arginine at codon 330 of the FANCC protein (p.Ser330Arg). The serine residue is weakly conserved and there is a moderate physicochemical difference between serine and arginine. This variant is present in population databases (rs374915316, ExAC 0.02%). This variant has not been reported in the literature in individuals with FANCC-related disease. ClinVar contains an entry for this variant (Variation ID: 422336). 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: "Deleterious"; PolyPhen-2: "Benign"; 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.