Associated disorders

The KCNJ2 gene is associated with autosomal dominant Andersen-Tawil syndrome, also known as long QT syndrome (LQTS), type 7 (MedGen UID: 327586), short QT syndrome (SQTS) (MedGen UID: 400662), and catecholaminergic polymorphic ventricular tachycardia (CPVT) (PMID: 22589293). Additionally, the KCNJ2 gene has preliminary evidence supporting a correlation with autosomal dominant atrial fibrillation (MedGen UID: 462781).

Pathogenic KCNJ2 variants are associated with ~60% of clinical cases of Andersen-Tawil syndrome, a subtype of LQTS. Overall, KCNJ2 is associated with an unknown percentage of clinical cases of LQTS. KCNJ2 is also a rare cause of SQTS and causes an unknown percentage of CPVT and atrial fibrillation cases.

The KCNJ2 gene encodes the potassium inwardly-rectifying channel, subfamily J, member 2. The electrical activity of muscle is controlled by the movement of potassium, sodium, and calcium ions across the cardiac muscle cells. Pathogenic variants in genes that encode potassium channels or subunits are a common cause of inherited cardiac arrhythmias.

  1. Smith, AH, et al. Andersen-Tawil syndrome. Indian Pacing Electrophysiol J. 2006; 6(1):32-43. doi: 10.1016/j.hrthm.2006.08.015. PMID: 16943893
  2. Statland, JM, et al. Andersen-Tawil Syndrome. 2004 Nov 22. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: http://www.ncbi.nlm.nih.gov/books/NBK1264/ PMID: 20301441
  3. Lieve, KV, et al. Results of genetic testing in 855 consecutive unrelated patients referred for long QT syndrome in a clinical laboratory. Genet Test Mol Biomarkers. 2013; 17(7):553-61. doi: 10.1089/gtmb.2012.0118. PMID: 23631430
  4. Jabbari, J, et al. New exome data question the pathogenicity of genetic variants previously associated with catecholaminergic polymorphic ventricular tachycardia. Circ Cardiovasc Genet. 2013; 6(5):481-9. doi: 10.1161/CIRCGENETICS.113.000118. PMID: 24025405
  5. Vega, AL, et al. Protein kinase A-dependent biophysical phenotype for V227F-KCNJ2 mutation in catecholaminergic polymorphic ventricular tachycardia. Circ Arrhythm Electrophysiol. 2009; 2(5):540-7. doi: 10.1161/CIRCEP.109.872309. PMID: 19843922
  6. Kimura, H, et al. Phenotype variability in patients carrying KCNJ2 mutations. Circ Cardiovasc Genet. 2012; 5(3):344-53. doi: 10.1161/CIRCGENETICS.111.962316. PMID: 22589293
  7. Priori, SG, et al. A novel form of short QT syndrome (SQT3) is caused by a mutation in the KCNJ2 gene. Circ. Res. 2005; 96(7):800-7. PMID: 15761194
  8. Hattori, T, et al. A novel gain-of-function KCNJ2 mutation associated with short-QT syndrome impairs inward rectification of Kir2.1 currents. Cardiovasc. Res. 2012; 93(4):666-73. PMID: 22155372

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
KCNJ2 NM_000891.2