ClinVar Miner

Submissions for variant NM_000142.4(FGFR3):c.1949A>C (p.Lys650Thr) (rs121913105)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics,Fulgent Genetics RCV000763123 SCV000893668 pathogenic Achondroplasia; Camptodactyly, tall stature, and hearing loss syndrome; Carcinoma of cervix; Crouzon syndrome with acanthosis nigricans; Levy-Hollister syndrome; Muenke syndrome; Thanatophoric dysplasia type 1; Thanatophoric dysplasia, type 2; Bladder cancer, somatic; Hypochondroplasia; Epidermal nevus; Severe achondroplasia with developmental delay and acanthosis nigricans; Malignant tumor of testis; Carcinoma of colon 2018-10-31 criteria provided, single submitter clinical testing
GeneReviews RCV000056100 SCV000087172 pathologic Hypochondroplasia 2013-09-26 no assertion criteria provided curation Converted during submission to Pathogenic.
Invitae RCV000542319 SCV000640368 pathogenic Craniosynostosis 2018-05-08 criteria provided, single submitter clinical testing This sequence change replaces lysine with threonine at codon 650 of the FGFR3 protein (p.Lys650Thr). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and threonine. This variant is not present in population databases (rs121913105, ExAC no frequency). This variant has been reported to segregate with disease in multiple families affected with acanthosis nigricans (PMID: 17875876, 26818779, 25809207). It has also been shown to segregate with disease in a large family affected with hypochondroplasia and acanthosis nigricans (PMID: 18583390). Experimental studies have shown that this missense change causes constitutive tyrosine kinase activation (PMID: 11055896). For these reasons, this variant has been classified as Pathogenic.

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