ClinVar Miner

Submissions for variant NM_023067.4(FOXL2):c.650C>T (p.Ser217Phe)

dbSNP: rs797044527
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000521611 SCV000617544 pathogenic not provided 2023-10-23 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect, showing an increased transactivation activity (PMID: 19010791, 19515849, 18372316); Identified in multiple unrelated individuals with features of blepharophimosis-ptosis-epicanthus inversus syndrome referred for genetic testing at GeneDx and in the published literature (PMID: 11468277); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 19515849, 18372316, 22312189, 20067892, 19010791, 11468277)
Labcorp Genetics (formerly Invitae), Labcorp RCV000521611 SCV003525369 pathogenic not provided 2022-08-16 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Ser217 amino acid residue in FOXL2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17277738, 19515849, 22312189). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on FOXL2 function (PMID: 18372316, 19010791). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 180594). This missense change has been observed in individual(s) with blepharophimosis (PMID: 11468277, 31077882). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 217 of the FOXL2 protein (p.Ser217Phe).
GeneReviews RCV000192032 SCV000207358 not provided Blepharophimosis, ptosis, and epicanthus inversus syndrome no assertion provided literature only
Wessex Regional Genetics Laboratory, Salisbury District Hospital RCV000192032 SCV000924428 likely pathogenic Blepharophimosis, ptosis, and epicanthus inversus syndrome 2018-01-01 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.