ClinVar Miner

Submissions for variant NM_000142.4(FGFR3):c.1948A>C (p.Lys650Gln) (rs78311289)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital RCV000017757 SCV000692268 pathogenic Hypochondroplasia 2015-01-23 no assertion criteria provided clinical testing
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
GeneReviews RCV000017757 SCV000086723 pathologic Hypochondroplasia 2013-09-26 no assertion criteria provided curation Converted during submission to Pathogenic.
Invitae RCV000527452 SCV000640367 pathogenic Craniosynostosis 2017-10-16 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.
OMIM RCV000017757 SCV000038035 pathogenic Hypochondroplasia 2007-12-15 no assertion criteria provided literature only
OMIM RCV000144153 SCV000189233 pathogenic Bladder cancer, somatic 2007-12-15 no assertion criteria provided literature only

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