Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001213304 | SCV001384930 | pathogenic | Lethal congenital glycogen storage disease of heart | 2022-03-18 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with isoleucine, which is neutral and non-polar, at codon 290 of the PRKAG2 protein (p.Lys290Ile). ClinVar contains an entry for this variant (Variation ID: 943169). This missense change has been observed in individual(s) with Wolff-Parkinson-White syndrome and ventricular hypertrophy (PMID: 28690312). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. 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. |