Total submissions: 8
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 | |
Gene |
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 |
RCV000437923 | SCV000505531 | likely pathogenic | Bladder carcinoma | 2015-07-14 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000430843 | SCV000510405 | likely pathogenic | Acanthosis nigricans | 2016-05-13 | no assertion criteria provided | literature only | |
Clinical Molecular Genetics Laboratory, |
RCV000017757 | SCV000692268 | pathogenic | Hypochondroplasia | 2015-01-23 | no assertion criteria provided | clinical testing |