Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003770305 | SCV004573431 | likely pathogenic | Hypogonadotropic hypogonadism 2 with or without anosmia; Pfeiffer syndrome | 2023-05-16 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 97 of the FGFR1 protein (p.Gly97Arg). This missense change has been observed in individual(s) with idiopathic hypogonadotropic hypogonadism and/or Kallmann syndrome (PMID: 30098700). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Gly97 amino acid residue in FGFR1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 18985070, 23154428, 31200363). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on FGFR1 function (PMID: 32666525). 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) performed at Invitae indicates that this missense variant is expected to disrupt FGFR1 protein function. ClinVar contains an entry for this variant (Variation ID: 974816). |
| Department of Urology, |
RCV001251092 | SCV001426682 | likely pathogenic | Hypogonadotropic hypogonadism 2 with or without anosmia | no assertion criteria provided | research |