Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001203605 | SCV001374778 | uncertain significance | Lethal congenital glycogen storage disease of heart | 2022-08-21 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with PRKAG2-related conditions. 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. 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 expected to disrupt PRKAG2 protein function. ClinVar contains an entry for this variant (Variation ID: 935090). This variant is present in population databases (rs763144065, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 120 of the PRKAG2 protein (p.Arg120Cys). |
| Color Diagnostics, |
RCV001525625 | SCV001735796 | uncertain significance | Cardiomyopathy | 2022-12-09 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with cysteine at codon 120 of the PRKAG2 protein. Computational prediction 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). 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 been identified in 1/251214 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. |
| Mayo Clinic Laboratories, |
RCV003480988 | SCV004224125 | uncertain significance | not provided | 2023-03-27 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV004010630 | SCV004842306 | uncertain significance | Hypertrophic cardiomyopathy | 2024-09-27 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with cysteine at codon 120 of the PRKAG2 protein. Computational prediction 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). 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 been identified in 1/251214 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 | RCV004033578 | SCV005026299 | uncertain significance | Cardiovascular phenotype | 2023-09-30 | criteria provided, single submitter | clinical testing | The p.R120C variant (also known as c.358C>T), located in coding exon 3 of the PRKAG2 gene, results from a C to T substitution at nucleotide position 358. The arginine at codon 120 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |