ClinVar Miner

Submissions for variant NM_016203.4(PRKAG2):c.1516G>C (p.Glu506Gln) (rs267606978)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000211740 SCV000204030 likely pathogenic Hypertrophic cardiomyopathy 2013-02-13 criteria provided, single submitter clinical testing proposed classification - variant undergoing re-assessment, contact laboratory
GeneDx RCV000159017 SCV000208959 likely pathogenic not provided 2016-10-03 criteria provided, single submitter clinical testing The E506Q likely pathogenic variant in the PRKAG2 gene has been reported in an infant with ventricular pre-excitation and severe biventricular hypertrophic cardiomyopathy, and was found to segregate with a cardiomyopathy phenotype in two relatives (Kelly et al., 2009). In addition, E506Q is classified in ClinVar as a likely pathogenic variant by an external clinical laboratory that identified this variant de novo in an individual with cardiomyopathy; the variant also segregated with disease in one additional family member (SCV000204030.3; Landrum et al., 2016). This variant was also identified in our laboratory in an individual with HCM and segregated with the phenotype in one family member. Furthermore, the E506Q variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. E506Q is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Furthermore, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Finally, a different missense variant at the same residue (E506K) has been identified as likely pathogenic by GeneDx as well as reported in the Human Gene Mutation Database in association with cardiomyopathy (Stenson et al., 2014), thus supporting the functional importance of this region of the protein.
OMIM RCV000007258 SCV000027454 pathogenic Familial hypertrophic cardiomyopathy 6 2009-11-01 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.