Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000805827 | SCV000945799 | uncertain significance | Lethal congenital glycogen storage disease of heart | 2024-04-25 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 503 of the PRKAG2 protein (p.Gln503Arg). This variant is present in population databases (rs727504337, gnomAD 0.003%). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy and/or sudden infant death syndrome (PMID: 27532257, 32789579). ClinVar contains an entry for this variant (Variation ID: 177820). 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, |
RCV001184475 | SCV001350448 | uncertain significance | Cardiomyopathy | 2023-06-08 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamine with arginine at codon 503 of the PRKAG2 protein. Computational prediction suggests that this variant may have a 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 been reported in an individual affected with hypertrophic cardiomyopathy (PMID: 25611685, 27532257). It has also been reported in an individual affected with sudden death in infancy (PMID: 32789579). This variant has been identified in 3/251486 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. |
| Fulgent Genetics, |
RCV002498739 | SCV002775523 | uncertain significance | Lethal congenital glycogen storage disease of heart; Hypertrophic cardiomyopathy 6; Wolff-Parkinson-White pattern | 2021-08-17 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV003998249 | SCV004842207 | uncertain significance | Hypertrophic cardiomyopathy | 2023-11-30 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamine with arginine at codon 503 of the PRKAG2 protein. Computational prediction suggests that this variant may have a 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 been reported in an individual affected with hypertrophic cardiomyopathy (PMID: 25611685, 27532257). It has also been reported in an individual affected with sudden death in infancy (PMID: 32789579). This variant has been identified in 3/251486 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. |
| Laboratory for Molecular Medicine, |
RCV000154453 | SCV000204122 | uncertain significance | not specified | 2013-02-13 | no assertion criteria provided | clinical testing | proposed classification - variant undergoing re-assessment, contact laboratory |