ClinVar

Description

The R217G variant has been reported in association with paraganglioma-pheochromocytoma syndrome(Sanso et al., 2012; van et al. 2009). The R217G substitution was not observed in approximately 6,500individuals of European and African American ancestry in the NHLBI Exome Sequencing Project,indicating it is not a common benign variant in these populations. The R217G variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residuesdiffer in polarity, charge, size and/or other properties. This substitution occurs at a position that isconserved across species. In silico analysis predicts this variant is probably damaging to the proteinstructure/function. Missense variants in this residue (R217G and R217L) and in nearby residues (G208E,Q214H, A215T, W218S, D224H) have been reported in the Human Gene Mutation Database inassociation with SDHB-related disorders (Stenson et al., 2014), supporting the functional importance of thisregion of the protein. Therefore, we consider this variant to be pathogenic.