Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000417539 | SCV000535593 | uncertain significance | not provided | 2017-01-13 | criteria provided, single submitter | clinical testing | The R2489G variant in the CDH23 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. However, a missense variant in same codon (R2489H) has been reported in an individual with hearing loss and no second variant identified, and in an individual with retinitis pigmentosa who also had a second missense variant (Wagatsuma et al., 2007; Zhao et al., 2015). The R2489G 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. The R2489G 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. We interpret R2489G as a variant of uncertain significance. |