ClinVar Miner

Submissions for variant NM_022970.3(FGFR2):c.1087+1305C>G (rs121918496)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000535651 SCV000659605 pathogenic FGFR2 related craniosynostosis 2018-08-08 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tryptophan at codon 342 of the FGFR2 protein (p.Cys342Trp). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tryptophan. This variant is not present in population databases (rs121918496, ExAC no frequency). This variant has been reported in individuals affected with Crouzon syndrome or Pfeiffer syndrome (PMID: 8528214, 16418739, 24127277, 25271085), and was observed to be de novo in several of these individuals (PMID: 7607643, 11781872). ClinVar contains an entry for this variant (Variation ID: 13275). Multiple different missense substitutions at this codon (p.Cys342Ser, p.Cys342Tyr, p.Cys342Arg) have been determined to be pathogenic (PMID: 24127277). An experimental study has shown that the cysteine at codon 342 forms a disulfide bond that is important for FGFR2 folding, and that disrupting this cysteine leads to higher levels of protein activity (PMID: 9539778). This suggests that the cysteine residue is critical for FGFR2 protein function, and that missense substitutions at this position may be pathogenic. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000014195 SCV000034443 pathogenic Crouzon syndrome 1997-02-01 no assertion criteria provided literature only

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.