Total submissions: 15
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000194803 | SCV000247374 | pathogenic | Craniosynostosis syndrome | 2015-07-27 | criteria provided, single submitter | clinical testing | |
Genomic Diagnostic Laboratory, |
RCV000017726 | SCV000328409 | pathogenic | Crouzon syndrome-acanthosis nigricans syndrome | 2016-10-20 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000414319 | SCV000491018 | pathogenic | not provided | 2021-11-01 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a lower expression of the protein in comparison to wild-type and an increase in the phosphorylation level (Chen et al., 2011); Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 23727984, 9857065, 18976668, 23437153, 21536014, 27228464, 17935505, 27181494, 29620724, 8880573, 31016899, 31837199, 10670894, 7493034, 11426459, 20199409) |
Ambry Genetics | RCV000623005 | SCV000741461 | pathogenic | Inborn genetic diseases | 2016-04-18 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000414319 | SCV000762843 | pathogenic | not provided | 2023-09-24 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 391 of the FGFR3 protein (p.Ala391Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with Crouzon syndrome with acanthosis nigricans (CSAN) (PMID: 7493034, 8880573, 11426459, 20199409). ClinVar contains an entry for this variant (Variation ID: 16329). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on FGFR3 protein function. Experimental studies have shown that this missense change affects FGFR3 function (PMID: 18976668, 21536014, 23437153). For these reasons, this variant has been classified as Pathogenic. |
Baylor Genetics | RCV000017726 | SCV000807312 | pathogenic | Crouzon syndrome-acanthosis nigricans syndrome | 2017-09-01 | criteria provided, single submitter | clinical testing | This mutation has been previously reported as disease-causing and was found once in our laboratory de novo in a 2-year-old female with Crouzon syndrome |
Department of Medical Genetics, |
RCV000017726 | SCV001437560 | pathogenic | Crouzon syndrome-acanthosis nigricans syndrome | criteria provided, single submitter | clinical testing | ||
Revvity Omics, |
RCV000414319 | SCV002023068 | pathogenic | not provided | 2021-03-10 | criteria provided, single submitter | clinical testing | |
Seattle Children's Hospital Molecular Genetics Laboratory, |
RCV000414319 | SCV002525631 | pathogenic | not provided | criteria provided, single submitter | clinical testing | The c.1172C>A variant, located in exon 9 of FGFR3, results in a substitution of alanine with glutamic acid at position 391 of the protein. This is a recurrent pathogenic variant that has previously been reported in several individuals with Crouzon syndrome with acanthosis nigricans (PMID: 7493034, 8880573, 17935505, 31016899, NBK1455). In these reports, common clinical features include craniosynostosis, ocular proptosis, midface hypoplasia, choanal atresia or stenosis, hydrocephalus, and acanthosis nigricans. Other features such as Chiari malformations, vertebral anomalies, and subtle skeletal findings have also been reported. This variant is absent from large population cohorts (0 of >281,000 alleles; Genome Aggregation Database v2.1). The Ala391Glu change has been experimentally demonstrated to cause an increase in FGFR3 activation by means of FGFR3 dimer stabilization and phosphorylation of critical tyrosines in the FGFR3 activation loop (PMID: 23437153). | |
Institute of Human Genetics, |
RCV000017726 | SCV004027639 | pathogenic | Crouzon syndrome-acanthosis nigricans syndrome | 2023-07-10 | criteria provided, single submitter | clinical testing | Criteria applied: PS2,PS4,PS3_MOD,PM2_SUP,PP3 |
OMIM | RCV000017726 | SCV000038004 | pathogenic | Crouzon syndrome-acanthosis nigricans syndrome | 2007-11-01 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000439126 | SCV000510403 | likely pathogenic | Carcinoma | 2016-05-13 | no assertion criteria provided | literature only | |
Clinical Molecular Genetics Laboratory, |
RCV000017726 | SCV000692267 | pathogenic | Crouzon syndrome-acanthosis nigricans syndrome | 2009-12-24 | no assertion criteria provided | clinical testing | |
Genome Diagnostics Laboratory, |
RCV000414319 | SCV001807532 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000414319 | SCV001971435 | pathogenic | not provided | no assertion criteria provided | clinical testing |