ClinVar Miner

Submissions for variant NM_005691.3(ABCC9):c.4640C>T (p.Thr1547Ile) (rs387906805)

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
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769372 SCV000900760 uncertain significance Cardiomyopathy 2017-06-26 criteria provided, single submitter clinical testing
Loeys Lab,Universiteit Antwerpen RCV001375633 SCV001572558 uncertain significance Hypertrophic cardiomyopathy 2021-02-26 criteria provided, single submitter clinical testing This sequence change results in a missense variant in the ABCC9 gene (p.(Thr1547Ile)). This variant is not present in population databases (absent from GnomAD; PM2). This variant has been reported in the literature in individuals with atrial fibrillation(Olsen et. al; 2007). Functional data are available: Patch-clamp analysis demonstrated that the variant compromised ATP-dependent induction of K-current. Kir6.2-Knock-out mice developed AF in response to adrenergic stimulus. (Olsen et. al; 2007; PS3). Prediction programs showed conflicting results (Align GVGD: G0; PolyPhen-2HumDiv and HumVar: benign; SIFT: tolerated; Mutation taster: disease causing). The variant affects a highly conserved nucleotide and weakly conserved amino acid. The variant was identified in a family with HCM, however it did not show segregation with the HCM-phenotype (BS4). In conclusion this variant was classified as a variant of unknown significance according to ACMG-guidelines (Conflicting results: PM2,PS3, BS4).
OMIM RCV000023103 SCV000044394 pathogenic Atrial fibrillation, familial, 12 2007-02-01 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.