Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000038951 | SCV000062629 | uncertain significance | not specified | 2012-07-06 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Benign. The Ser207Cys varia nt in PRKAG2 has not been reported in the literature nor previously identified i n >1500 Caucasian probands tested by our laboratory. In addition, this variant h as not been identified in large and broad populations by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS). This low frequency is consistent with a disease causing role but insufficient to establish this with confidence. Computational analyses (biochemical amino acid properties, conservation, AlignG VGD, PolyPhen2, and SIFT) suggest that the Ser207Cys variant may not impact the protein, though this information is not predictive enough to rule out pathogenic ity. In addition, the variant is located outside the CBS domain of the PRKAG2 pr otein that contains all pathogenic PRKAG2 variants have been identified to date. Additional information is needed to fully assess the clinical significance of the Ser207Cys variant. |
Illumina Laboratory Services, |
RCV000371199 | SCV000467636 | uncertain significance | Lethal congenital glycogen storage disease of heart | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV001795010 | SCV000467637 | uncertain significance | Wolff-Parkinson-White pattern | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000331754 | SCV000467638 | uncertain significance | Familial Hypertrophic Cardiomyopathy with Wolff-Parkinson-White Syndrome | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000371199 | SCV001214023 | uncertain significance | Lethal congenital glycogen storage disease of heart | 2021-12-02 | criteria provided, single submitter | clinical testing | 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 not expected to disrupt PRKAG2 protein function. ClinVar contains an entry for this variant (Variation ID: 45729). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 27532257, 32746448). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 207 of the PRKAG2 protein (p.Ser207Cys). |
Fulgent Genetics, |
RCV002477108 | SCV002779105 | uncertain significance | Lethal congenital glycogen storage disease of heart; Hypertrophic cardiomyopathy 6; Wolff-Parkinson-White pattern | 2021-09-09 | criteria provided, single submitter | clinical testing |