ClinVar Miner

Submissions for variant NM_000142.5(FGFR3):c.2420G>T (p.Ter807Leu)

dbSNP: rs397515514
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000478851 SCV000568541 pathogenic not provided 2022-08-08 criteria provided, single submitter clinical testing Variant resulting in loss of the termination codon leading to protein extension by 101 amino acids; Identified in patients with thanatophoric dysplaisa in published literature (Passos-Bueno et al., 1999); Multiple other variants resulting in loss of termination codon and protein extension reported in association with thanatophoric dysplasia (HGMD); Several different variants resulting in similar protein extensions have been reported in the Human Gene Mutation Database associated with thanatophoric dysplasia (HGMD), and have apparently similar functional consequences on protein stability and/or processing (Bonaventure et al., 2007; Gibbs et al., 2007); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25614871, 25728633, 20301540, 33942288, 9677066, 10425034, 17509076, 17320202)
Labcorp Genetics (formerly Invitae), Labcorp RCV000478851 SCV000640376 pathogenic not provided 2020-01-14 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Several other stop codon variants (p.*807Glyext*101, p.*807Argext*101, p.*807Cysext*101) have also been described in individuals with thanatophoric dysplasia type I, which result in the same length of a cysteine-rich, highly hydrophobic elongation at the C-terminus of FGFR3 protein (PMID: 7647778, 25614871). In addition, one of these variants (p.*807Argext*101) has been reported to disrupt the protein function and determined to be pathogenic (PMID: 17509076). This variant has been reported in the literature in individuals affected with thanatophoric dysplasia type I (PMID: 10425034, 25728633). This variant is also known as X807L and *807Leuext*102 in the literature. ClinVar contains an entry for this variant (Variation ID: 65562). This variant is not present in population databases (ExAC no frequency). This sequence change disrupts the translational stop signal of the FGFR3 mRNA. It is expected to replace the original stop signal with a leucine residue and extend the length of the FGFR3 protein by 101 additional amino acid residues (p.*807Leuext*101).
Fulgent Genetics, Fulgent Genetics RCV002490635 SCV002779161 pathogenic Achondroplasia; Camptodactyly-tall stature-scoliosis-hearing loss syndrome; Cervical cancer; Crouzon syndrome-acanthosis nigricans syndrome; Levy-Hollister 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 2022-02-14 criteria provided, single submitter clinical testing
GeneReviews RCV000055764 SCV000086713 not provided Thanatophoric dysplasia type 1 no assertion provided literature only

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