Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV003311142 | SCV004007679 | uncertain significance | Cardiovascular phenotype | 2023-06-11 | criteria provided, single submitter | clinical testing | The p.S131F variant (also known as c.392C>T), located in coding exon 3 of the PRKAG2 gene, results from a C to T substitution at nucleotide position 392. The serine at codon 131 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003507499 | SCV004309507 | uncertain significance | Lethal congenital glycogen storage disease of heart | 2023-07-17 | 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 not expected to disrupt PRKAG2 protein function. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 131 of the PRKAG2 protein (p.Ser131Phe). |