ClinVar Miner

Submissions for variant NM_005751.4(AKAP9):c.11519T>C (p.Ile3840Thr) (rs145675748)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000170624 SCV000223176 likely benign not specified 2011-09-21 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000538694 SCV000627715 uncertain significance Long QT syndrome 2017-06-14 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 3840 of the AKAP9 protein (p.Ile3840Thr). The isoleucine residue is weakly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is present in population databases (rs145675748, ExAC 0.02%), 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 a AKAP9-related disease. ClinVar contains an entry for this variant (Variation ID: 190498). 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, this variant has uncertain impact on AKAP9 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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