ClinVar Miner

Submissions for variant NM_023110.3(FGFR1):c.1558G>A (p.Ala520Thr)

gnomAD frequency: 0.00001  dbSNP: rs749758370
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centogene AG - the Rare Disease Company RCV001809018 SCV002059348 uncertain significance Osteoglophonic dysplasia 2017-12-04 criteria provided, single submitter clinical testing
GeneDx RCV003442910 SCV004170388 uncertain significance not provided 2023-04-17 criteria provided, single submitter clinical testing Reported in the heterozygous state in a patient with hypogonadotropic hypogonadism and anosmia or hyposmia (Albuisson et al., 2005); Not observed at significant frequency in large population cohorts (gnomAD); 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: 31996231, 19707180, 15605412, 23329143, 18034870)
Labcorp Genetics (formerly Invitae), Labcorp RCV003772262 SCV004607425 uncertain significance Hypogonadotropic hypogonadism 2 with or without anosmia; Pfeiffer syndrome 2023-06-15 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. 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. ClinVar contains an entry for this variant (Variation ID: 1333803). This missense change has been observed in individual(s) with Kallmann syndrome (PMID: 15605412). This variant is present in population databases (rs749758370, gnomAD 0.003%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 520 of the FGFR1 protein (p.Ala520Thr).

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