Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000805827 | SCV000945799 | uncertain significance | Lethal congenital glycogen storage disease of heart | 2021-09-02 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine with arginine at codon 503 of the PRKAG2 protein (p.Gln503Arg). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and arginine. This variant is present in population databases (rs727504337, ExAC 0.003%). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 27532257). ClinVar contains an entry for this variant (Variation ID: 177820). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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 | |
| 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 |