ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.1283C>A (p.Pro428His)

dbSNP: rs199889477
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
Ambry Genetics RCV000163906 SCV000214500 benign Hereditary cancer-predisposing syndrome 2022-01-31 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae RCV000529447 SCV000632832 uncertain significance Birt-Hogg-Dube syndrome 2024-01-18 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with histidine, which is basic and polar, at codon 428 of the FLCN protein (p.Pro428His). This variant is present in population databases (rs199889477, gnomAD 0.01%). This missense change has been observed in individual(s) with FLCN-related conditions (PMID: 36095024). ClinVar contains an entry for this variant (Variation ID: 184619). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt FLCN protein function with a negative predictive value of 80%. 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.
GeneDx RCV001544699 SCV001763877 uncertain significance not provided 2022-11-23 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Identified in a patient with renal cell carcinoma and sebaceous gland hyperplasia (Leetanapon and Laodheerasiri, 2022); This variant is associated with the following publications: (PMID: 17028174, Leetanapon2022, 24728327, 26415585)
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV001544699 SCV002009965 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002492651 SCV002781120 uncertain significance Birt-Hogg-Dube syndrome; Familial spontaneous pneumothorax; Potocki-Lupski syndrome; Nonpapillary renal cell carcinoma; Colorectal cancer 2021-07-07 criteria provided, single submitter clinical testing
Baylor Genetics RCV000529447 SCV004199795 uncertain significance Birt-Hogg-Dube syndrome 2023-09-21 criteria provided, single submitter 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.