ClinVar Miner

Submissions for variant NM_023110.3(FGFR1):c.1408C>T (p.Arg470Cys)

gnomAD frequency: 0.00007  dbSNP: rs781310679
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001551032 SCV001771453 uncertain significance not provided 2024-07-17 criteria provided, single submitter clinical testing Identified in a patient with normosmic idiopathic hypogonadotrpic hypogonadism and classified as a variant of uncertain significance in published literature (PMID: 27884859, 30921766); Identified in a patients with Kallmann syndrome and classified as a variant of uncertain significance in published literature (PMID: 37805574, 36531499); Identified in a patient with mild Pfeiffer syndrome in published literature (PMID: 25873011); 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: 30921766, 36531499, 27884859, 37805574, 25873011)
Fulgent Genetics, Fulgent Genetics RCV002501889 SCV002816805 uncertain significance Hypogonadotropic hypogonadism 2 with or without anosmia; Jackson-Weiss syndrome; Pfeiffer syndrome; Hartsfield-Bixler-Demyer syndrome; Osteoglophonic dysplasia; Trigonocephaly 1; Encephalocraniocutaneous lipomatosis 2022-04-07 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002568326 SCV003029723 uncertain significance Hypogonadotropic hypogonadism 2 with or without anosmia; Pfeiffer syndrome 2023-10-14 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 470 of the FGFR1 protein (p.Arg470Cys). This variant is present in population databases (rs781310679, gnomAD 0.03%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with FGFR1-related conditions (PMID: 27884859, 30921766). ClinVar contains an entry for this variant (Variation ID: 1190350). 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.
Reproductive Endocrine Unit, Massachusetts General Hospital RCV003234576 SCV003932559 uncertain significance Hypogonadotropic hypogonadism 2 with or without anosmia 2023-05-04 criteria provided, single submitter research The variant has been classified as VUS based on the variant meeting the following ACMG Criteria: PP2,BP4.

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