Submissions for variant NM_023110.3(FGFR1):c.532T>C (p.Cys178Arg)

dbSNP: rs2150914598

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001916796	SCV002188789	uncertain significance	Hypogonadotropic hypogonadism 2 with or without anosmia; Pfeiffer syndrome	2021-10-15	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. This variant disrupts the p.Cys178 amino acid residue in FGFR1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16757108, 27596331). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This missense change has been observed in individual(s) with autosomal dominant FGFR1-related conditions (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with arginine at codon 178 of the FGFR1 protein (p.Cys178Arg). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and arginine.
Reproductive Endocrine Unit, Massachusetts General Hospital	RCV003234585	SCV003932513	uncertain significance	Hypogonadotropic hypogonadism 2 with or without anosmia	2023-05-04	criteria provided, single submitter	research