Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001184068 | SCV001349941 | uncertain significance | Cardiomyopathy | 2023-11-30 | criteria provided, single submitter | clinical testing | This missense variant replaces leucine with phenylalanine at codon 159 of the PRKAG2 protein. Computational prediction tools indicate that this variant has a neutral impact on protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with PRKAG2-related disorders in the literature. This variant has not been identified 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 |
RCV001363141 | SCV001559241 | uncertain significance | Lethal congenital glycogen storage disease of heart | 2022-11-02 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 159 of the PRKAG2 protein (p.Leu159Phe). This variant is not present in population databases (gnomAD no frequency). 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: 923392). 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 | RCV003163436 | SCV003855211 | uncertain significance | Cardiovascular phenotype | 2023-01-22 | criteria provided, single submitter | clinical testing | The p.L159F variant (also known as c.475C>T), located in coding exon 4 of the PRKAG2 gene, results from a C to T substitution at nucleotide position 475. The leucine at codon 159 is replaced by phenylalanine, an amino acid with highly 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. |
| All of Us Research Program, |
RCV004008428 | SCV004842289 | uncertain significance | Hypertrophic cardiomyopathy | 2024-01-08 | criteria provided, single submitter | clinical testing | This missense variant replaces leucine with phenylalanine at codon 159 of the PRKAG2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has not been identified 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. |