ClinVar

Description

p.Ile11Thr (ATC>ACC): c.32 T>C in exon 1 of the RYR2 gene (NM_001035.2). The Ile11Thr variant in the RYR2 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Ile11Thr results in a non-conservative amino acid substitution of a non-polar Isoleucine residue with a polar Threonine residue at a position that is conserved across species. The Ile11Thr variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. However, in silico analysis was inconsistent with regard to the effect this variant may have on the protein structure/function. In addition, no mutations affecting nearby residues have been reported in the RYR2 gene in association with CPVT, indicating this region of the protein may be tolerant of change. We cannot definitively determine if Ile11Thr is a disease-causing mutation or a rare benign variant. The variant is found in CPVT panel(s).