Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000538769 | SCV000627718 | uncertain significance | Long QT syndrome | 2017-04-13 | criteria provided, single submitter | clinical testing | In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. 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: "Probably Damaging"; Align-GVGD: "Class C0"). This variant is present in population databases (rs777495335, ExAC 0.01%) but has not been reported in the literature in individuals with an AKAP9-related disease. This sequence change replaces glutamic acid with valine at codon 423 of the AKAP9 protein (p.Glu423Val). The glutamic acid residue is moderately conserved and there is a moderate physicochemical difference between glutamic acid and valine. |