ClinVar Miner

Submissions for variant NM_005751.4(AKAP9):c.1685A>G (p.His562Arg) (rs145033147)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000171575 SCV000055227 uncertain significance not provided 2013-06-24 criteria provided, single submitter research
Invitae RCV000805832 SCV000945804 uncertain significance Long QT syndrome 2018-08-02 criteria provided, single submitter clinical testing This sequence change replaces histidine with arginine at codon 562 of the AKAP9 protein (p.His562Arg). The histidine residue is weakly conserved and there is a small physicochemical difference between histidine and arginine. This variant is present in population databases (rs145033147, ExAC 0.03%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with AKAP9-related disease. ClinVar contains an entry for this variant (Variation ID: 191383). 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 arginine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.

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