ClinVar Miner

Submissions for variant NM_000142.5(FGFR3):c.2005C>G (p.Arg669Gly)

dbSNP: rs1490564667
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001567755 SCV000832202 uncertain significance not provided 2024-11-23 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 669 of the FGFR3 protein (p.Arg669Gly). This variant is present in population databases (no rsID available, gnomAD 0.005%). This missense change has been observed in individual(s) with hypochondroplasia (PMID: 15863034). ClinVar contains an entry for this variant (Variation ID: 579912). Invitae Evidence Modeling incorporating data from in vitro experimental studies (internal data) indicates that this missense variant is expected to disrupt FGFR3 function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects FGFR3 function (PMID: 26992226). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV001567755 SCV001791499 uncertain significance not provided 2025-02-04 criteria provided, single submitter clinical testing Observed in patients with hypochondroplasia in published literature; detailed clinical information and segregation analysis was not provided for one of the individuals (PMID: 15863034, 37806643); Reported to increase autophosphorylation in a study of activating cancer variants; no patient with skeletal dysplasia reported (PMID: 26992226); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28755412, 30545934, 38411226, 30355600, 26992226, 15863034, 37806643)
Blueprint Genetics RCV001567755 SCV001832401 uncertain significance not provided 2019-11-30 criteria provided, single submitter clinical testing
Juno Genomics, Hangzhou Juno Genomics, Inc RCV004796287 SCV005418851 uncertain significance Achondroplasia; Camptodactyly-tall stature-scoliosis-hearing loss syndrome; Cervical cancer; Crouzon syndrome-acanthosis nigricans syndrome; Muenke syndrome; Thanatophoric dysplasia type 1; Thanatophoric dysplasia, type 2; Malignant tumor of urinary bladder; Hypochondroplasia; Epidermal nevus; Severe achondroplasia-developmental delay-acanthosis nigricans syndrome; Colorectal cancer; Germ cell tumor of testis; LADD syndrome 1 criteria provided, single submitter clinical testing PM2_Supporting+PP3+PS4_Supporting+PS3_Supporting
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV001567755 SCV002036876 uncertain significance not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV001567755 SCV002037451 uncertain significance not provided no assertion criteria provided clinical testing

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