ClinVar Miner

Submissions for variant NM_000142.4(FGFR3):c.1948A>G (p.Lys650Glu) (rs78311289)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255799 SCV000322322 pathogenic not provided 2017-01-18 criteria provided, single submitter clinical testing The K650E missense variant in the FGFR3 gene has been reported previously in association with thanatophoric dysplasia and observed as de novo events (Tavormina et al., 1995; Huang et al., 2013). Functional studies indicate K650E results in constitutive autophosphorylation and activation of the receptor (Webster et al. 1997; Otsuka et al. 2011). The K650E missense variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. It is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. Other pathogenic missense variants in this residue (K650N, K650M, K650Q, K650T) have been reported in the Human Gene Mutation Database in association with skeletal dysplasias (Stenson et al., 2014), further supporting the functional importance of this residue in the protein.
OMIM RCV000017728 SCV000038006 pathogenic Thanatophoric dysplasia, type 2 2009-11-01 no assertion criteria provided literature only
OMIM RCV000017729 SCV000038007 pathogenic Multiple myeloma 2009-11-01 no assertion criteria provided literature only
OMIM RCV000017730 SCV000038008 pathogenic Spermatocytic seminoma 2009-11-01 no assertion criteria provided literature only
GeneReviews RCV000017728 SCV000086708 pathologic Thanatophoric dysplasia, type 2 2013-09-12 no assertion criteria provided curation Converted during submission to Pathogenic.
Database of Curated Mutations (DoCM) RCV000433411 SCV000510408 likely pathogenic Carcinoma 2016-05-13 no assertion criteria provided literature only
Baylor Genetics RCV000017728 SCV000854612 pathogenic Thanatophoric dysplasia, type 2 2018-11-18 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.