• Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit




Associated disorders

The KCNQ1 gene is associated with autosomal dominant long QT syndrome (LQTS), type 1 (MedGen UID: 19831), atrial fibrillation (MedGen UID: 373232), short QT syndrome (SQTS) (MedGen UID: 355890) and autosomal recessive Jervell and Lange-Nielsen syndrome (JLNS) (MedGen UID: 5929). For information about the location of a KCNQ1 variant, please visit www.invitae.com/KCNQ1-topology.

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Pathogenic KCNQ1 variants are associated with 90% of clinical cases of Jervell and Lange-Nielsen syndrome, a subtype of LQTS. Overall, KCNQ1 is associated with 40% of clinical cases of LQTS. Pathogenic KCNQ1 variants also are rare causes of atrial fibrillation and SQTS.

The KCNQ1 gene encodes the potassium voltage-gated channel subfamily KQT member 1. Potassium channels control the flow of potassium ions in cardiac muscle. The electrical activity of cardiac muscle is controlled by the movement of potassium, sodium and calcium ions across cardiac muscle cell membranes. Mutations in genes that encode potassium channels are a common cause of inherited cardiac arrhythmias.

OMIM: 607542

Clinical condition
The KCNQ1 gene is associated with autosomal dominant long QT syndrome (LQTS) type 1 (MedGen UID: 19831), atrial fibrillation (MedGen UID: 373232), short QT syndrome (SQTS; MedGen UID: 355890), and autosomal recessive Jervell and Lange-Nielsen syndrome (JLNS; MedGen UID: 5929).

LQTS is a cardiac arrhythmia condition that primarily affects the electrical system of the heart. LQTS is defined by a prolonged QTc interval and T wave abnormalities on an ECG without the presence of any known structural heart disease. Individuals with LQTS can develop a specific abnormal heart rhythm called Torsade de pointes (PMID: 24011539).

Atrial fibrillation is an arrhythmia characterized by rapid, chaotic beats originating from the top chambers of the heart.

SQTS is also a cardiac arrhythmia condition that primarily affects the electrical system of the heart. SQTS is defined by a shortened QTc interval on an ECG. Individuals with SQTS can develop irregular and rapid heart rhythms initiating from the top (atrial) or bottom (ventricular) chambers of the heart (PMID: 24011539).

The abnormal heart beats in the above arrhythmia conditions can lead to palpitations, dizziness (pre-syncope), fainting (syncope), seizure-like activity and, in some cases, sudden cardiac arrest/death, including sudden infant death syndrome. Symptoms can present in both children and adults and may be triggered by homeostatic imbalance and/or the use of certain medications (PMID: 24011539).

JLNS is a multisystem disorder characterized by congenital bilateral sensorineural hearing loss in combination with a very prolonged QTc interval on ECG/EKG with a propensity for life-threatening ventricular arrhythmias and high risk for sudden cardiac death (PMID: 13435203). Onset of cardiac symptoms typically occurs early in childhood and can be triggered by intense exercise or emotional stress (PMID: 16461811). In addition to congenital hearing loss and cardiac symptoms, some individuals with JLNS have also been found to have anemia and elevated levels of the hormone gastrin (PMID: 22805636). Biallelic or digenic compound pathogenic sequence changes in KCNQ1 and KCNE1 predispose individuals to developing JLNS (PMID: 9354783).

Gene information
The KCNQ1 gene encodes the voltage-gated potassium channel subfamily KQT member 1. These proteins tetramerize and assemble with the KCNE1 gene product to form a channel that controls the flow of potassium ions in cardiac and inner ear cells. In cardiac muscle cells, these channels help regulate the electrical current that causes the heart to beat. In the inner ear, these channels produce a potassium-rich fluid, endolymph, that bathes the organ of Corti, which is essential for hearing. Pathogenic variants reduce the function of these channels disrupting the repolarization of cardiac action potential (leading to arrhythmias) and decreasing endolymph production (leading to deterioration of the organ of Corti; PMID: 9302275).

KCNQ1-related LQTS, SQTS, and atrial fibrillation exhibit autosomal dominant inheritance. This means that an individual with a pathogenic variant has a 50% chance of passing the variant on to their offspring. Carriers are at increased risk of developing autosomal dominant KCNQ1-related conditions and may have reproductive risks related to autosomal recessive KCNQ1-related conditions as well. It is now possible to identify at-risk relatives who can pursue testing for this specific familial variant.

KCNQ1-related JLNS exhibits autosomal recessive inheritance, and affected individuals have two pathogenic variants-one in each copy of their KCNQ1 genes (biallelic homozygous or compound heterozygous) or one pathogenic variant in one copy of KCNQ1 in combination with a pathogenic variant in one copy of KCNE1 (digenic). Affected individuals with homozygous or compound heterozygous JLNS will pass one pathogenic variant to all of their children who will inherit a predisposition for LQTS, SQTS, and atrial fibrillation. Biallelic affected individuals may pass on one, both, or zero of their pathogenic variants to each offspring. Reproductive risk for offspring depends on both the patient’s and his/her partner’s variant status.

KCNQ1-related LQTS, SQTS, and atrial fibrillation exhibit reduced penetrance, while JLNS has shown almost full penetrance in affected individuals (PMID: 12736279, 16461811).

Screening and management recommendations include the following:

  • Cardiac examination including calculation of QTc (PMID: 29097296, 24011539)
  • KCNQ1-related arrhythmia is recommended to be managed depending on clinical presentation and may include:
    • Lifestyle modification: avoidance of certain sports, activities, or medications (CredibleMeds. www.crediblemeds.org. Accessed February 15, 2018), avoidance of physical or emotional stress, and maintenance of homeostatic balance (PMID: 24011539)
    • Medications (PMID: 29097296, 24011539)
    • Device therapy (pacemaker, implantable defibrillator; PMID:29097296, 24011539)
    • Surgical therapy (denervation)
  • Clinical genetics consultation to discuss genetic testing for at-risk family members and reproductive risks (PMID: 29097296, 24011539)
    Additional screens for those with JLNS include:
  • Audiology evaluation to establish the extent of hearing loss
    • Cochlear implantation may be used as treatment for hearing loss with special precaution taken to minimize cardiac events during surgery (PMID: 11140992)
  • Complete blood count to screen for anemia and potential iron deficiency
    • Treatment of iron deficiency anemia should follow standard guidelines (PMID: 22805636)

Review date: February 2018

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 and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below. In addition, the analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
KCNQ1 NM_000218.2