ClinVar

Description

The L1363H missense substitution has not been published as a pathogenic variant nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,200 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. L1363H 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 conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, no missense variants in nearby residues have been reported in the Human Gene Mutation Database (Stenson et al., 2014). Additionally, few pathogenic missense variants have been reported in CHARGE syndrome, as most pathogenic variants introduce a premature termination codon.