Description
The R718G variant in the FGFR1 gene has not been reported previously as a pathogenic variant nor as a benign polymorphism, to our knowledge. The R718G substitution was not observed in approximately6400 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project,indicating it is not a common benign variant in these populations. The R718G variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is well-conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in nearby residues (M719R, P722Y, C725Y) as well as a missense variant in the same residue (R718C) have been reported in the Human Gene Mutation Database in association with Kallmann syndrome and Hartsfield syndrome (Stenson et al., 2014), supporting thefunctional importance of this region of the protein. We interpret R718G as a pathogenic variant.
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | germline | yes | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |
