Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000182661 | SCV000235039 | uncertain significance | not provided | 2016-09-02 | criteria provided, single submitter | clinical testing | A novel variant of uncertain significance has been identified in the RYR2 gene. The D179N variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant was not observed in approximately 6,100 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. D179N is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species and is located in one of the three hot-spot regions of the RYR2 gene, where the majority of pathogenic missense variants occur (Medeiros-Domingo et al., 2009). Consequently, in silico analysis predicts this variant is probably damaging to the protein structure/function. However, additional evidence such as segregation and functional data is necessary to fully assess the pathogenicity of this variant. |