Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000159022 | SCV000208964 | uncertain significance | not provided | 2013-09-24 | criteria provided, single submitter | clinical testing | p.Glu569Lys (GAG>AAG): c.1705 G>A in exon 16 of the PRKAG2 gene (NM_016203.3) The Glu569Lys variant in the PRKAG2 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Glu569Lys results in a non-conservative amino acid substitution of a negatively charged Glutamic acid residue with a positively charged Lysine residue at a position that is conserved across species. The Glu569Lys variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. However, in silico analysis was inconsistent with regard to the effect this variant may have on the protein structure/function.. Furthermore, Glu569Lys occurs at the last amino acid of the protein, and no nearby mutations have been reported in association with HCM, indicating this region of the protein may be tolerant of change.With the clinical and molecular information available at this time, we cannot definitively determine if Glu569Lys is a disease-causing mutation or a rare benign variant. The variant is found in HCM panel(s). |
| Invitae | RCV001303314 | SCV001492555 | uncertain significance | Lethal congenital glycogen storage disease of heart | 2022-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 569 of the PRKAG2 protein (p.Glu569Lys). This variant is present in population databases (rs730880983, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with PRKAG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 181482). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PRKAG2 protein function. 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. |
| Ambry Genetics | RCV003298188 | SCV003997321 | uncertain significance | Cardiovascular phenotype | 2023-03-31 | criteria provided, single submitter | clinical testing | The p.E569K variant (also known as c.1705G>A), located in coding exon 16 of the PRKAG2 gene, results from a G to A substitution at nucleotide position 1705. The glutamic acid at codon 569 is replaced by lysine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |