Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001894002 | SCV002121647 | uncertain significance | Lethal congenital glycogen storage disease of heart | 2021-04-14 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with arginine at codon 344 of the PRKAG2 protein (p.His344Arg). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and arginine. This variant has not been reported in the literature in individuals 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 expected to disrupt PRKAG2 protein function. |
All of Us Research Program, |
RCV004009201 | SCV004829120 | uncertain significance | Hypertrophic cardiomyopathy | 2023-06-26 | criteria provided, single submitter | clinical testing | This missense variant replaces histidine with arginine at codon 344 of the PRKAG2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, 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. |