Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001824894 | SCV002074319 | uncertain significance | not specified | 2022-01-17 | criteria provided, single submitter | clinical testing | Variant summary: AKAP9 c.3736A>G (p.Arg1246Gly) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 8.2e-06 in 242950 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.3736A>G has been reported in the literature in one individual affected with Primary Electrical Disease (Proost_2017). The report does not provide unequivocal conclusions about association of the variant with Long QT Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Ambry Genetics | RCV002363178 | SCV002624188 | uncertain significance | Cardiovascular phenotype | 2024-03-11 | criteria provided, single submitter | clinical testing | The p.R1246G variant (also known as c.3736A>G), located in coding exon 11 of the AKAP9 gene, results from an A to G substitution at nucleotide position 3736. The arginine at codon 1246 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. |
| Fulgent Genetics, |
RCV002487864 | SCV002786831 | uncertain significance | Long QT syndrome 11 | 2021-09-29 | criteria provided, single submitter | clinical testing | |
| Dept of Medical Biology, |
RCV003318388 | SCV004022019 | uncertain significance | Long QT syndrome | 2024-01-08 | criteria provided, single submitter | research | Criteria: PM2, BP4 |
| Invitae | RCV003318388 | SCV004398660 | uncertain significance | Long QT syndrome | 2022-11-07 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 666370). This missense change has been observed in individual(s) with clinical features of AKAP9-related conditions (PMID: 28341588). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 1246 of the AKAP9 protein (p.Arg1246Gly). |