Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002907689 | SCV003244397 | uncertain significance | Hypogonadotropic hypogonadism 2 with or without anosmia; Pfeiffer syndrome | 2022-10-07 | criteria provided, single submitter | clinical testing | 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. 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 not expected to disrupt FGFR1 protein function. This missense change has been observed in individual(s) with Kallmann syndrome (PMID: 33548149). This variant is present in population databases (rs530348127, gnomAD 0.04%). This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 534 of the FGFR1 protein (p.Met534Val). |