ClinVar Miner

Submissions for variant NM_001453.3(FOXC1):c.256C>T (p.Leu86Phe)

dbSNP: rs886039568
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 RCV000255576 SCV000322419 pathogenic not provided 2022-10-12 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect (reduced capacity for DNA binding and transactivation) (Saleem RA et al., 2003); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 14578375, 27535533, 28513611)
Invitae RCV000416497 SCV003439266 pathogenic Axenfeld-Rieger syndrome type 3 2023-12-06 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 86 of the FOXC1 protein (p.Leu86Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with Axenfeld-Rieger syndrome (PMID: 14578375, 17197537, 28513611). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 265478). 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 expected to disrupt FOXC1 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects FOXC1 function (PMID: 14506133, 14578375, 32631953). For these reasons, this variant has been classified as Pathogenic.
Genetics and Molecular Pathology, SA Pathology RCV000416497 SCV000494253 likely pathogenic Axenfeld-Rieger syndrome type 3 2016-03-11 no assertion criteria provided clinical testing Missense; predicted to affect function by multiple algorithms (SIFT, PolyPhen), demonstrates reduced transactivation (Saleem et al., 2003), hightly conserved region, conservation throughout FOX gene family

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.