ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.792T>G (p.Ser264Arg) (rs730881717)

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
GeneDx RCV000586258 SCV000211043 uncertain significance not provided 2017-10-09 criteria provided, single submitter clinical testing This variant is denoted FANCC c.792T>G at the cDNA level, p.Ser264Arg (S264R) at the protein level, and results in the change of a Serine to an Arginine (AGT>AGG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. FANCC Ser264Arg was not observed at a significant allele frequency in large population cohorts (Lek 2016). Since Serine and Arginine differ in some properties, this is considered a semi-conservative amino acid substitution. FANCC Ser264Arg occurs at a position that is not conserved and is located within the Hsp70 and GRP94 binding domains (Gordon 2000). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether FANCC Ser264Arg is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000206295 SCV000259465 uncertain significance Fanconi anemia 2018-09-05 criteria provided, single submitter clinical testing This sequence change replaces serine with arginine at codon 264 of the FANCC protein (p.Ser264Arg). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and arginine. This variant is present in population databases (rs730881717, ExAC 0.009%). This variant has not been reported in the literature in individuals with FANCC-related disease. ClinVar contains an entry for this variant (Variation ID: 182477). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine 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.
Integrated Genetics/Laboratory Corporation of America RCV000586258 SCV000695437 uncertain significance not provided 2017-06-16 criteria provided, single submitter clinical testing Variant summary: The FANCC c.792T>G (p.Ser264Arg) variant involves the alteration of a non-conserved nucleotide. 3/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 6/121088 control chromosomes at a frequency of 0.0000496, which does not exceed the estimated maximal expected allele frequency of a pathogenic FANCC variant (0.0017678). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.

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.