ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.580C>T (p.Arg194Trp) (rs138070947)

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
Ambry Genetics RCV000130128 SCV000184960 likely benign Hereditary cancer-predisposing syndrome 2018-03-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Subpopulation frequency in support of benign classification,Other data supporting benign classification
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000226985 SCV000298049 uncertain significance Multiple fibrofolliculomas 2016-07-18 criteria provided, single submitter clinical testing
Invitae RCV000226985 SCV000291447 uncertain significance Multiple fibrofolliculomas 2018-11-16 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 194 of the FLCN protein (p.Arg194Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs138070947, ExAC 0.03%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with FLCN-related disease. ClinVar contains an entry for this variant (Variation ID: 141552). 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: "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.