ClinVar Miner

Submissions for variant NM_023110.3(FGFR1):c.817G>A (p.Val273Met)

dbSNP: rs1131691929
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000492969 SCV000583162 likely pathogenic not provided 2024-12-10 criteria provided, single submitter clinical testing 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: 27699475, 23329143, 23643382, 15605412, 16764984, 18160472, 19707180, 17624596, 18034870, 37980453, 33354214, 33548149, 37805574, 38227553)
Labcorp Genetics (formerly Invitae), Labcorp RCV001851361 SCV002178538 pathogenic Hypogonadotropic hypogonadism 2 with or without anosmia; Pfeiffer syndrome 2024-03-01 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 273 of the FGFR1 protein (p.Val273Met). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal dominant Kallmann syndrome (PMID: 15605412, 16764984; Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 430370). 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. For these reasons, this variant has been classified as Pathogenic.
Reproductive Endocrine Unit, Massachusetts General Hospital RCV003234560 SCV003932535 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: PM2,PP3,PP1,PP4.

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