Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000158998 | SCV000208939 | uncertain significance | not provided | 2019-01-10 | criteria provided, single submitter | clinical testing | The R186W variant of uncertain significance in the PRKAG2 gene has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). R186W is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Additional evidence is needed to clarify the pathogenicity of this variant, including observation in a significant number of affected individuals, segregation data, and functional evidence.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign. |
Color Diagnostics, |
RCV001186247 | SCV001352620 | uncertain significance | Cardiomyopathy | 2022-12-07 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with tryptophan at codon 186 of the PRKAG2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 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 cardiovascular disorders in the literature. This variant has been identified in 5/251482 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. |
Invitae | RCV001239320 | SCV001412189 | likely benign | Lethal congenital glycogen storage disease of heart | 2023-10-04 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002345545 | SCV002650905 | uncertain significance | Cardiovascular phenotype | 2021-02-19 | criteria provided, single submitter | clinical testing | The p.R186W variant (also known as c.556C>T), located in coding exon 4 of the PRKAG2 gene, results from a C to T substitution at nucleotide position 556. The arginine at codon 186 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Fulgent Genetics, |
RCV002484989 | SCV002789133 | uncertain significance | Lethal congenital glycogen storage disease of heart; Hypertrophic cardiomyopathy 6; Wolff-Parkinson-White pattern | 2021-11-05 | criteria provided, single submitter | clinical testing |