Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000756984 | SCV000884994 | uncertain significance | not provided | 2018-03-15 | criteria provided, single submitter | clinical testing | The AKAP9 c.8585A>G; p.Gln2862Arg variant (rs752618658), to our knowledge, is not reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is listed in the genome Aggregation Database (gnomAD) with a Latino population frequency of 0.04% (identified on 12 out of 32,090 chromosomes). The glutamine at position 2862 is highly conserved, considering 11 species, and computational analyses of the effects of the p.Gln2862Arg variant on protein structure and function do not predict a deleterious effect (SIFT: tolerated, PolyPhen-2: benign). Based on the available information, the clinical significance of the p.Gln2862Arg variant cannot be determined with certainty. |
| Labcorp Genetics |
RCV001324827 | SCV001515793 | uncertain significance | Long QT syndrome | 2023-06-10 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 618523). This variant has not been reported in the literature in individuals affected with AKAP9-related conditions. This variant is present in population databases (rs752618658, gnomAD 0.04%). This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 2862 of the AKAP9 protein (p.Gln2862Arg). |
| Ambry Genetics | RCV004993991 | SCV005584135 | likely benign | Cardiovascular phenotype | 2024-10-07 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |