Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000687370 | SCV000814933 | likely pathogenic | Lethal congenital glycogen storage disease of heart | 2024-01-31 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 548 of the PRKAG2 protein (p.Ser548Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with PRKAG2-related conditions (PMID: 32646569; Invitae). This variant is also known as c.1642T>G. ClinVar contains an entry for this variant (Variation ID: 567324). 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 with a positive predictive value of 80%. This variant disrupts the p.Ser548 amino acid residue in PRKAG2. Other variant(s) that disrupt this residue have been observed in individuals with PRKAG2-related conditions (PMID: 16487706, 32646569; Invitae), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |