Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000621262 | SCV000737669 | uncertain significance | Cardiovascular phenotype | 2023-10-08 | criteria provided, single submitter | clinical testing | The p.R528K variant (also known as c.1583G>A), located in coding exon 8 of the AKAP9 gene, results from a G to A substitution at nucleotide position 1583. The arginine at codon 528 is replaced by lysine, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species, and lysine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV002531777 | SCV003004541 | uncertain significance | Long QT syndrome | 2022-05-05 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with AKAP9-related conditions. ClinVar contains an entry for this variant (Variation ID: 519305). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The lysine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 528 of the AKAP9 protein (p.Arg528Lys). This variant is not present in population databases (gnomAD no frequency). |