ClinVar

Description

The R1195H variant of uncertain significance in the FBN2 gene has not been published as pathogenic or been reported as benign to our knowledge. R1195H is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R1195H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved in mammals, however, H1195 is the wild-type residue in at least one species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Finally, although located within a calcium-binding EGF-like domain of the FBN2 gene, the R1195H variant does not affect a Cysteine residue. Cysteine substitutions in the calcium-binding EGF-like domains represent the majority of pathogenic missense changes associated with congenital contractural arachnodactyly (Frédéric et al., 2009).