ClinVar

Description

A variant of uncertain significance has been identified in the TGFB3 gene. The Y390F variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is notobserved in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015;Exome Variant Server). The Y390F variant is a non-conservative amino acid substitution, which islikely to impact secondary protein structure as these residues differ in polarity, charge, size and/orother properties. This substitution occurs at a position that is conserved across species, and in silicoanalysis predicts this variant is probably damaging to the protein structure/function. Nevertheless, nomissense variants in nearby residues have been reported in the Human Gene Mutation Database inassociation with TGFB3-related disorders (Stenson et al., 2014). Thus, this variant lacks observationin a significant number of affected individuals, segregation data, and functional evidence, which would further clarify its pathogenicity.