ClinVar Miner

Submissions for variant NM_000142.5(FGFR3):c.1948A>C (p.Lys650Gln) (rs78311289)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000527452 SCV000640367 pathogenic Craniosynostosis syndrome 2019-02-18 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamine at codon 650 of the FGFR3 protein (p.Lys650Gln). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamine. This variant is present in population databases (rs78311289, ExAC 0.01%). This variant has been reported in several individuals affected with hypochondroplasia with or without acanthosis nigricans and/or hyperinsulinemia (PMID: 11055896, 16912704, 20453470, 21510009). In at least one individual, the variant arose de novo (PMID: 11055896). ClinVar contains an entry for this variant (Variation ID: 16348). An experimental study has shown that this missense change results in increased FGFR3 auto-phosphorylation in vitro (PMID: 11055896). For these reasons, this variant has been classified as Pathogenic.
Mendelics RCV000017757 SCV001136685 uncertain significance Hypochondroplasia 2019-05-28 criteria provided, single submitter clinical testing
OMIM RCV000017757 SCV000038035 pathogenic Hypochondroplasia 2007-12-15 no assertion criteria provided literature only
GeneReviews RCV000017757 SCV000086723 pathologic Hypochondroplasia 2013-09-26 no assertion criteria provided curation Converted during submission to Pathogenic.
OMIM RCV000144153 SCV000189233 pathogenic Urinary bladder cancer 2007-12-15 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000437923 SCV000505531 likely pathogenic Bladder carcinoma 2015-07-14 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000430843 SCV000510405 likely pathogenic Acanthosis nigricans 2016-05-13 no assertion criteria provided literature only
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital RCV000017757 SCV000692268 pathogenic Hypochondroplasia 2015-01-23 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.