Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000379458 | SCV000473633 | likely benign | Craniosynostosis syndrome | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. |
| Labcorp Genetics |
RCV003766087 | SCV004603472 | uncertain significance | Hypogonadotropic hypogonadism 2 with or without anosmia; Pfeiffer syndrome | 2023-06-29 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs186746130, gnomAD 0.02%). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 248 of the FGFR1 protein (p.Val248Met). This variant has not been reported in the literature in individuals affected with FGFR1-related conditions. 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: 362899). |