Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000414388 | SCV000490417 | pathogenic | not provided | 2015-08-19 | criteria provided, single submitter | clinical testing | The G23E variant in the ATP2A2 gene has been published previously in several patients with Darier disease (Ikeda et al., 2003; Sakuntabhai 1999; Harboe et al., 2011). It was also 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. G23E 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 and in-silico analysis predicts this variant is probably damaging to the protein structure/function. In addition, functional studies of the G23E mutation have shown that it results in misfolding of the protein leading to reduced protein expression, and to increased cellular stress and apoptosis in keratinocytes (Wang et al., 2011; Dode et al., 2003). Therefore we interpret G23E in ATP2A2 as a pathogenic variant. |
| OMIM | RCV000019367 | SCV000039657 | pathogenic | Keratosis follicularis | 1999-03-01 | no assertion criteria provided | literature only |