Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001191047 | SCV001358718 | uncertain significance | Cardiomyopathy | 2024-07-25 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with glycine at codon 454 of the PRKAG2 protein. Computational prediction tools indicate that this variant's impact on protein structure and function is inconclusive. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with PRKAG2 syndrome (PMID: 32646569). This variant has been identified in 2/282878 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Labcorp Genetics |
RCV002559183 | SCV003253174 | uncertain significance | Lethal congenital glycogen storage disease of heart | 2024-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 454 of the PRKAG2 protein (p.Glu454Gly). This variant is present in population databases (no rsID available, gnomAD 0.1%). This missense change has been observed in individual(s) with PRKAG2-related conditions (PMID: 32646569). ClinVar contains an entry for this variant (Variation ID: 927650). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt PRKAG2 protein function with a negative predictive value of 95%. 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. |
| All of Us Research Program, |
RCV004010477 | SCV004842216 | uncertain significance | Hypertrophic cardiomyopathy | 2024-08-13 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with glycine at codon 454 of the PRKAG2 protein. Computational prediction tool is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 2/282878 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV004986924 | SCV005477164 | uncertain significance | Cardiovascular phenotype | 2024-08-01 | criteria provided, single submitter | clinical testing | The p.E454G variant (also known as c.1361A>G), located in coding exon 12 of the PRKAG2 gene, results from an A to G substitution at nucleotide position 1361. The glutamic acid at codon 454 is replaced by glycine, an amino acid with similar properties. This alteration has been reported in a PRKAG2 genetic testing cohort (Lopez-Sainz A et al. J Am Coll Cardiol, 2020 Jul;76:186-197). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |