ClinVar Miner

Submissions for variant NM_023110.3(FGFR1):c.646A>G (p.Ile216Val)

gnomAD frequency: 0.00001  dbSNP: rs763771933
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001205279 SCV001376524 uncertain significance Hypogonadotropic hypogonadism 2 with or without anosmia; Pfeiffer syndrome 2023-11-25 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 216 of the FGFR1 protein (p.Ile216Val). This variant is present in population databases (rs763771933, gnomAD 0.003%). This missense change has been observed in individual(s) with hypogonadotropic hypogonadism (PMID: 26708526). ClinVar contains an entry for this variant (Variation ID: 936473). 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.
GeneDx RCV001760168 SCV001988935 uncertain significance not provided 2021-01-04 criteria provided, single submitter clinical testing Identified in the heterozygous state in an individual with isolated hypogonadotrophic hypogonadism, however, this variant was also present in the unaffected mother and an unaffected sibling (Nair et al., 2016); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 26708526)

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.