Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000182763 | SCV000235148 | uncertain significance | not provided | 2016-08-26 | criteria provided, single submitter | clinical testing | A novel K2619E variant of uncertain significance was identified in the RYR2 gene. It has not been published as a pathogenic variant or as a benign variant to our knowledge. The K2619E variant was not observed in approximately 5,900 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 K2619E 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 predicts this variant is probably damaging to the protein structure/function. However, although another missense variant in a nearby residue (G2628E) has been reported in the Human Gene Mutation Database in association with CPVT (Stenson et al., 2014), the clinical significance of this variant is unknown. Furthermore, segregation and functional data is not available to fully assess the pathogenicity of the K2619E variant. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign. |