ClinVar Miner

Submissions for variant NM_023110.3(FGFR1):c.1349C>T (p.Ser450Phe)

dbSNP: rs2150675272
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001756579 SCV001986029 uncertain significance not provided 2019-12-09 criteria provided, single submitter clinical testing Reported in a patient with septo-optic dysplasia in published literature (Raivio et al., 2012); Published functional studies suggest this variant impacts signaling (Raivio et al., 2012); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 22319038)
Labcorp Genetics (formerly Invitae), Labcorp RCV003771912 SCV004573849 uncertain significance Hypogonadotropic hypogonadism 2 with or without anosmia; Pfeiffer syndrome 2023-07-13 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 450 of the FGFR1 protein (p.Ser450Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with septo optic dysplasia (PMID: 22319038). ClinVar contains an entry for this variant (Variation ID: 1303080). 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. Experimental studies have shown that this missense change affects FGFR1 function (PMID: 22319038). 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.

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