ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.739C>T (p.Leu247Phe)

gnomAD frequency: 0.00001  dbSNP: rs1554835099
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000522448 SCV000616714 uncertain significance not provided 2022-12-28 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: Gordon2000[Book])
Ambry Genetics RCV001026382 SCV001188750 uncertain significance Hereditary cancer-predisposing syndrome 2022-05-24 criteria provided, single submitter clinical testing The p.L247F variant (also known as c.739C>T), located in coding exon 7 of the FANCC gene, results from a C to T substitution at nucleotide position 739. The leucine at codon 247 is replaced by phenylalanine, an amino acid with highly similar properties. This alteration was identified in an individual diagnosed with ovarian cancer (Song H et al. J Med Genet, 2021 05;58:305-313). This amino acid position is highly 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.
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV001198452 SCV001369386 uncertain significance Fanconi anemia complementation group C 2019-10-30 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PM2,PP3.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV000522448 SCV002010152 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Invitae RCV001857936 SCV002148153 uncertain significance Fanconi anemia 2022-05-24 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 247 of the FANCC protein (p.Leu247Phe). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FANCC-related conditions. ClinVar contains an entry for this variant (Variation ID: 449020). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or 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.
Natera, Inc. RCV001198452 SCV001458705 uncertain significance Fanconi anemia complementation group C 2020-09-16 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.