Test Catalog

Test ID: PMARP    
Postmortem Arrhythmia Panel, Varies

Useful For Suggests clinical disorders or settings where the test may be helpful

Providing a postmortem genetic evaluation in the setting of sudden unexplained death and suspicion for long QT or Brugada syndrome


Identification of a pathogenic variant in the decedent, which may assist with risk assessment and predictive testing of at-risk family members

Genetics Test Information Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test includes next-generation sequencing and supplemental Sanger sequencing to evaluate the AKAP9, ANK2,CACNA1C, CACNA2D1, CACNB2, CAV3, GPD1L, KCNE1, KCNE2, KCNE3, KCNH2, KCNJ2, KCNJ5, KCNJ8, KCNQ1, SCN1B, SCN3B, SCN4B, SCN5A, and SNTA1 genes.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Sudden cardiac death (SCD) is estimated to occur at an incidence of between 50 to 100 per 100,000 individuals in North America and Europe each year, claiming between 250,000 and 450,000 lives in the United States annually. In younger individuals (ages 15-35), the incidence of SCD is between 1 to 2 per 100,000 young individuals. The reported incidence of SCD is likely an underestimate since more overt causes of death, such as car accidents and drownings, may result from arrhythmogenic events. In cases of sudden unexplained death where autopsy does not detect a structural basis for sudden death, a hereditary arrhythmia may be suspected. Brugada syndrome (BrS) and long QT syndrome (LQTS) are inherited forms of cardiac arrhythmia that may cause sudden cardiac death. Postmortem diagnosis of a hereditary arrhythmia may assist in confirmation of the cause and manner of death, as well as risk assessment in living family members.


BrS is a genetic cardiac disorder characterized by ST segment elevation in leads V1-V3 on electrocardiography (EKG) with a high-risk for ventricular arrhythmias that can lead to sudden cardiac death. BrS is inherited in an autosomal dominant manner and is caused by pathogenic variants in genes that encode cardiac ion channels. The diagnosis of BrS is established based on the characteristic EKG abnormality along with personal and family health history, and also requires exclusion of other causes including cardiac structural abnormalities, medications, and electrolyte imbalances. Genes associated with BrS include CACNA1C, CACNA2D1, GPD1L, KCNE3, KCNJ8, SCN3B, CACNB2, SCN1B, and SCN5A. Additional clinical information about BrS can be found in MCL's BRGGP / Brugada Syndrome Multi-Gene Panel, Blood test.


LQTS is a genetic cardiac disorder characterized by QT prolongation and T-wave abnormalities on EKG, and may result in recurrent syncope, ventricular arrhythmia, and sudden cardiac death. Romano-Ward syndrome (RWS), which accounts for the majority of LQTS, follows an autosomal dominant inheritance pattern and is caused by pathogenic variants in genes that encode cardiac ion channels or associated proteins. The diagnosis of RWS is established by the prolongation of the QTc interval in the absence of other conditions or factors that may lengthen it, such as QT-prolonging drugs or structural heart abnormalities. Clinical factors such as a history of syncope and family history also contribute to the diagnosis of RWS. LQTS may also be associated with congenital profound bilateral sensorineural hearing loss, a condition known as Jervell and Lange-Nielsen syndrome (JLNS). JLNS is inherited in an autosomal recessive inheritance pattern and is caused by homozygous or compound heterozygous pathogenic variants in either the KCNQ1 or KCNE1 genes. Timothy syndrome (TS) is a multisystem disorder involving prolonged QT interval in association with congenital anomalies. TS is inherited in an autosomal dominant manner and usually occurs as a result of a de novo heterozygous variant in the CACNA1C gene. Genes associated with LQTS include AKAP9, ANK2, CACNA1C, CAV3, KCNE1, KCNE2, KCNH2, KCNJ2, KCNJ5, KCNQ1, SCN4B, SCN5A, and SNTA1. Additional clinical information about LQTS can be found in MCL's ID LQTGP / Long QT Syndrome Multi-Gene Panel, Blood test.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation Provides information to assist in interpretation of the test results

Evaluation and categorization of variants is performed using the most recent published American College of Medical Genetics recommendations as a guideline. Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.   


Multiple in silico evaluation tools may be used to assist in the interpretation of these results. The accuracy of predictions made by in silico evaluation tools is highly dependent upon the data available for a given gene, and predictions made by these tools may change over time. Results from in silico evaluation tools should be interpreted with caution and professional clinical judgment.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Sample Quality:

This test is intended for use when EDTA whole blood is not available and formalin-fixed, paraffin-embedded (FFPE) tissue or blood spots are the only available samples. DNA extracted from FFPE tissue can be degraded, which results in a higher failure rate (approximately 5%) for next-generation sequencing when compared to DNA extracted from whole blood. Due to the quality of DNA extracted from FFPE, the acceptable coverage threshold is lower than that of the equivalent blood assays. Coverage of at least 40X is expected for all regions assessed but may be adjusted on a case-by-case basis at the discretion of the laboratory director. Sanger sequencing may be used in regions that do not achieve this rate of coverage at the discretion of laboratory director. Genomic regions that are not sufficiently covered for analysis and interpretation will be indicated on the laboratory report. Sanger sequencing on DNA extracted from FFPE may also result in quality limitations when compared to testing on DNA extracted from blood.


Clinical Correlations:

Some individuals who have involvement of 1 or more of the genes on the panel may have a variant that is not identified by the methods used (eg, promoter mutations, deep intronic mutations). The absence of a variant, therefore, does not eliminate the possibility of long QT syndrome, Brugada syndrome, or a related disorder.


Test results should be interpreted in context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.


If testing was performed because of a family history of long QT syndrome, Brugada syndrome or a related disorder, it is often useful to first test an affected family member. Identification of a pathogenic variant in an affected individual allows for more informative testing of at-risk individuals.


Technical Limitations:

Next-generation sequencing may not detect all types of genetic variants. Additionally, rare variants may be present that could lead to false-negative or false-positive results. If results do not match clinical findings, consider alternative methods for analyzing these genes.


For blood spot samples: If the patient has had an allogeneic blood or marrow transplant or a recent (ie, <6 weeks from time of sample collection) heterologous blood transfusion, results may be inaccurate due to the presence of donor DNA.


Reclassification of Variants Policy:

At this time, it is not standard practice for the laboratory to systematically review likely pathogenic variants or variants of uncertain significance that are detected and reported. The laboratory encourages health care providers to contact the laboratory at any time to learn how the status of a particular variant may have changed over time.


Contact the laboratory if additional information is required regarding the transcript or human genome assembly used for the analysis of this patient's results.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Fishman GI, Chugh SS, DiMarco JP, et al: Sudden cardiac death prediction and prevention: report from the National Heart, Lung and Blood Institute and Heart Rhythm Society Workshop. Circulation 2010;122(22):2335-2348

2. Semsarian C, Ingles J: Molecular autopsy in victims of inherited arrhythmias. J Arrhythm 2016;32(5):359-365

3. Stattin EL, Westin IM, Cederquist K, et al: Genetic screening in sudden cardiac death in the young can save future lives. Int J Legal Med 2016;130(1):59-664

4. Ackerman MJ, Priori SG, Willems S, et al: HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies. Heart Rhythm 2011;8:1308-1339

Special Instructions Library of PDFs including pertinent information and forms related to the test