Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000223656 | SCV000272336 | uncertain significance | not specified | 2015-12-23 | criteria provided, single submitter | clinical testing | The p.Pro163Leu variant in PRKAG2 has not been previously reported in individual s with cardiomyopathy and was absent from large population studies. Computationa l prediction tools and conservation analysis suggest that this variant may impac t the protein, though this information is not predictive enough to determine pat hogenicity. In summary, the clinical significance of the p.Pro163Leu variant is uncertain. |
| Invitae | RCV000555477 | SCV000640346 | uncertain significance | Lethal congenital glycogen storage disease of heart | 2023-12-15 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 163 of the PRKAG2 protein (p.Pro163Leu). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 27532257). ClinVar contains an entry for this variant (Variation ID: 229172). 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 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. |
| Color Diagnostics, |
RCV001191617 | SCV001359503 | uncertain significance | Cardiomyopathy | 2023-07-25 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with leucine at codon 163 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 an individual affected with hypertrophic cardiomyopathy (PMID: 27532257). This variant has been identified in 3/251410 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 | RCV002338686 | SCV002638764 | uncertain significance | Cardiovascular phenotype | 2021-10-19 | criteria provided, single submitter | clinical testing | The p.P163L variant (also known as c.488C>T), located in coding exon 4 of the PRKAG2 gene, results from a C to T substitution at nucleotide position 488. The proline at codon 163 is replaced by leucine, an amino acid with similar properties. This alteration has been reported in a cardiomyopathy cohort; however, clinical details were limited (Walsh R et al. Genet Med, 2017 02;19:192-203). This amino acid position is highly conserved in available vertebrate species. 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. |