Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV001178706 | SCV001343218 | uncertain significance | Cardiomyopathy | 2023-04-25 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with serine at codon 368 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 1/247296 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 |
RCV001319964 | SCV001510730 | uncertain significance | Lethal congenital glycogen storage disease of heart | 2020-10-13 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs769212614, ExAC 0.002%). This sequence change replaces alanine with serine at codon 368 of the PRKAG2 protein (p.Ala368Ser). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and serine. This variant has not been reported in the literature in individuals with PRKAG2-related disease. 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. |
Ambry Genetics | RCV002429805 | SCV002742492 | uncertain significance | Cardiovascular phenotype | 2022-01-07 | criteria provided, single submitter | clinical testing | The p.A368S variant (also known as c.1102G>T), located in coding exon 10 of the PRKAG2 gene, results from a G to T substitution at nucleotide position 1102. The alanine at codon 368 is replaced by serine, an amino acid with similar 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. |
All of Us Research Program, |
RCV004006496 | SCV004842229 | uncertain significance | Hypertrophic cardiomyopathy | 2023-05-16 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with serine at codon 368 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 cardiovascular disorders in the literature. This variant has been identified in 1/247296 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. |