Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000413762 | SCV000491882 | uncertain significance | not specified | 2016-11-23 | criteria provided, single submitter | clinical testing | The E565Q variant in the PRKAG2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The E565Q variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The E565Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species, however, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret E565Q as a variant of uncertain significance. |
Color Diagnostics, |
RCV003532094 | SCV004359728 | uncertain significance | Cardiomyopathy | 2023-01-09 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with glutamine at codon 565 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 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. |
All of Us Research Program, |
RCV003995920 | SCV004826762 | uncertain significance | Hypertrophic cardiomyopathy | 2024-08-06 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with glutamine at codon 565 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 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. |