ClinVar Miner

Submissions for variant NM_005751.4(AKAP9):c.6896A>G (p.Glu2299Gly) (rs147841245)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000506888 SCV000602465 uncertain significance not provided 2017-05-26 criteria provided, single submitter clinical testing The p.Glu2299Gly variant (rs147841245) has not been reported in the medical literature nor has it been previously identified in our laboratory; however, it is listed in the ClinVar database as a variant of uncertain significance (Variation ID: 360836). It is listed in the Genome Aggregation Database (gnomAD) browser with a frequency in non-Finnish Europeans of 0.021% (identified in 27 out of 126,200 chromosomes). The glutamic acid at codon 2299 is highly conserved considering 11 species up to Cow (Alamut software v2.9), although computational analyses return mixed results regarding the effect of this variant on AKAP9 protein structure/function (SIFT: damaging, PolyPhen2: benign, and Mutation Taster: disease causing). Therefore, based on the available information, the clinical significance of the p.Glu2299Gly variant cannot be determined with certainty.
Illumina Clinical Services Laboratory,Illumina RCV000294466 SCV000470288 uncertain significance Romano-Ward syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000337725 SCV000470289 uncertain significance Long QT syndrome 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000337725 SCV000553470 uncertain significance Long QT syndrome 2018-04-16 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with glycine at codon 2299 of the AKAP9 protein (p.Glu2299Gly). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and glycine. This variant is present in population databases (rs147841245, ExAC 0.01%) but has not been reported in the literature in individuals with a AKAP9-related disease. ClinVar contains an entry for this variant (Variation ID: 360836). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. Because it is found in the population at an appreciable frequency, this variant is not anticipated to cause disease. However, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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