ClinVar

Description

The F215L pathogenic variant due to a C to G transversion at nucleotide 645 in the FOXG1 gene hasnot been reported previously as a pathogenic variant nor as a benign variant, to our knowledge.However, a female with congenital variant of Rett syndrome was found to be heterozygous for the denovo F215L variant due to a T to C transition at the same nucleotide position, denoted c.643C>T inthe publication due to alternate nomenclature (Mencarelli et al., 2010). The F215L variant was notobserved in approximately 6500 individuals of European and African American ancestry in theNHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.Although the F215L variant is a conservative amino acid substitution, it occurs at a position withinthe Fork-head DNA binding domain that is conserved across species and in silico analysis predicts thisvariant is probably damaging to the protein structure/function. We interpret F215L as a pathogenicvariant.