Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002768044 | SCV003584850 | uncertain significance | Inborn genetic diseases | 2021-09-27 | criteria provided, single submitter | clinical testing | The c.205G>A (p.D69N) alteration is located in exon 3 (coding exon 2) of the FGFR1 gene. This alteration results from a G to A substitution at nucleotide position 205, causing the aspartic acid (D) at amino acid position 69 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Reproductive Endocrine Unit, |
RCV003234598 | SCV003932463 | uncertain significance | Hypogonadotropic hypogonadism 2 with or without anosmia | 2023-05-04 | criteria provided, single submitter | research | |
Labcorp Genetics |
RCV003777735 | SCV004573097 | uncertain significance | Hypogonadotropic hypogonadism 2 with or without anosmia; Pfeiffer syndrome | 2023-08-30 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with FGFR1-related conditions. This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 69 of the FGFR1 protein (p.Asp69Asn). This variant is present in population databases (no rsID available, gnomAD 0.003%). ClinVar contains an entry for this variant (Variation ID: 2252300). 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. |