Submissions for variant NM_023110.3(FGFR1):c.83C>T (p.Pro28Leu)

gnomAD frequency: 0.00002  dbSNP: rs145434725

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000493590	SCV000583329	uncertain significance	not provided	2021-01-26	criteria provided, single submitter	clinical testing	Observed in a patient in published literature with nCHH who also harbored variants in other genes (Amato et al., 2019); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27896051, 31200363)
Invitae	RCV001856982	SCV002268381	uncertain significance	Hypogonadotropic hypogonadism 2 with or without anosmia; Pfeiffer syndrome	2023-11-21	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 28 of the FGFR1 protein (p.Pro28Leu). This variant is present in population databases (rs145434725, gnomAD 0.008%). This missense change has been observed in individual(s) with congenital hypogonadotropic hypogonadism (PMID: 31200363). ClinVar contains an entry for this variant (Variation ID: 430508). 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 FGFR1 protein function. 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.
Fulgent Genetics, Fulgent Genetics	RCV002496901	SCV002814226	uncertain significance	Hypogonadotropic hypogonadism 2 with or without anosmia; Jackson-Weiss syndrome; Pfeiffer syndrome; Hartsfield-Bixler-Demyer syndrome; Osteoglophonic dysplasia; Trigonocephaly 1; Encephalocraniocutaneous lipomatosis	2021-12-03	criteria provided, single submitter	clinical testing
Laboratory of Prof. Karen Avraham, Tel Aviv University	RCV004584731	SCV005073749	pathogenic	Hypogonadotropic hypogonadism 2 with or without anosmia	2024-05-08	criteria provided, single submitter	research	Pathogenic according to Deafness Variation Database
Breakthrough Genomics, Breakthrough Genomics	RCV000493590	SCV005195892	uncertain significance	not provided		criteria provided, single submitter	not provided