ClinVar

Description

p.Lys720Glu (AAG>GAG): c.2158 A>G in exon 9 of the RBM20 gene (NM_001134363.1). The K720E variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The K720E variant was not observed in approximately 2,300 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The K720E variant 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. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. A missense mutation in a nearby residue (R716Q) have been reported in association with cardiomyopathy, supporting the functional importance of this region of the protein. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in CARDIOMYOPATHY panel(s).