Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002367422 | SCV002666893 | uncertain significance | Cardiovascular phenotype | 2022-10-21 | criteria provided, single submitter | clinical testing | The p.M2372T variant (also known as c.7115T>C), located in coding exon 31 of the AKAP9 gene, results from a T to C substitution at nucleotide position 7115. The methionine at codon 2372 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Dept of Medical Biology, |
RCV003318418 | SCV004022010 | uncertain significance | Long QT syndrome | 2024-01-08 | criteria provided, single submitter | research | Criteria: PM2, BP4 |
Invitae | RCV003318418 | SCV004327745 | uncertain significance | Long QT syndrome | 2023-06-02 | 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 output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 1757237). This variant has not been reported in the literature in individuals affected with AKAP9-related conditions. This variant is present in population databases (rs749716365, gnomAD 0.002%). This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 2372 of the AKAP9 protein (p.Met2372Thr). |