Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, |
RCV000622391 | SCV000740495 | uncertain significance | Primary familial hypertrophic cardiomyopathy | 2017-07-04 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001248718 | SCV001422224 | uncertain significance | Lethal congenital glycogen storage disease of heart | 2023-11-30 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 561 of the PRKAG2 protein (p.Ala561Pro). This variant is present in population databases (rs61744760, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with PRKAG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 520490). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. |
Loeys Lab, |
RCV001375651 | SCV001572579 | uncertain significance | Primary dilated cardiomyopathy | 2021-02-26 | criteria provided, single submitter | clinical testing | This sequence change results in a missense variant in the PRKAG2 gene (p.(Ala561Pro)). This variant is present in population databases with a prevalence 1/249310in GnomAD). The variant has not been described before. The variant affects a moderately conserved nucleotide and weakly conserved amino acid. No functional data are available. Prediction programs show conflicting results (Align GVGD:C0,polymorphism; Polyphen-2-HumDiv: possibly damaging; Polyphen-2-HumVar: benign; SIFT: tolerated; Mutation Taster: disease causing). Another variant affecting the same amino acid (p.ala561Thr) has been classified as variant of unknown significance. This c.1681G>C variant was identified in a patient with DCM. No data on segregation are available. In conclusion this variant was classified as a variant of unknown significance according to ACMG-guidelines (insufficient data, criteria for other classification are not met). |