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Inherited Cardiovascular Diseases Testing by Next Generation Sequencing (NGS) – Saskatoon

Discipline

Genetics and Genomics

Overview

Description

Ordering recommendations

  • Inherited Cardiovascular Diseases Testing is diagnostic for cardiomyopathies, arrhythmias, related vascular and lipid disorders with suspected familial inheritance.
  • Medical Genetics can order all the subpanels on the requisition.
  • Currently, Cardiologist can only order panels with an asterisk (*) on the requisition (ie. Amyloidosis, Fabry disease, Marfan syndrome and Familial hypercholesterolemia). Cardiologist can refer patient to Medical Genetics to discuss testing for other subpanels.
  • DNA may also be extracted from peripheral blood at RRPL and sent to RUH Genomics Lab for testing

Ordering Requirements

Specimen Information

Specimen types accepted

  • Peripheral blood/whole blood
  • Genomic DNA extracted at RUH Genomics Lab or RRPL 
     

Specimen collection container

Collection procedure

  • Invert tube several times to mix
  • Specimen must be accompanied by a completed test requisition, signed by physician
  • Failure to include relevant patient information may result in test results being delayed or discontinued

Required volume

  • Optimal Volume: 4 - 7 mL
  • Minimum Volume: 2 mL

(Submitting the minimum volume makes it impossible to repeat the test or perform confirmatory/reflex testing. In some situations, a minimum volume may require a second collection.)

Transport and stability

  • Ship specimens at ambient temperature
  • Specimens may be stored at 2 - 8°C
     

Rejection criteria

Testing Information

Relevant clinical history

Patient history

  • Refer to requisition to fill out all relevant patient’s clinical symptoms that apply.

Performance

Methodology

  • Inherited Cardiovascular Diseases Testing is diagnostic for cardiomyopathies, arrhythmias, related vascular and lipid disorders with suspected familial inheritance. DNA is extracted from peripheral blood and subjected to library preparation using a customized Illumina TruSight Cardiovascular gene panel (204 genes) with Nextera Flex method and sequenced on an Illumina MiSeq.  Sequence reads are mapped and variants, including single nucleotide variants (SNV), small indels and copy number variants (CNV), are identified using a customized SOPHiA DDM bioinformatics pipeline.  Virtual gene panel is created according to the patient’s clinical phenotypes. Only variants in the coding sequence, 15 nucleotides upstream or downstream of each exon (+/-15), and specific deep intronic regions in the genes on the virtual panel are analyzed. Only pathogenic variants, likely pathogenic variants, and variants of unknown significance (VUS) are reported.  Benign and likely benign variants are not routinely reported. Sanger sequencing is used to fill-in low coverage regions, and to confirm reportable SNVs and small indels. Multiplex Ligation-dependent Probe Amplification (MLPA), qPCR or Chromosomal Microarray is used to confirm reportable CNVs. Variants are described following HGVS guidelines (GRCh37) and interpreted in accordance with ACMG/AMP guidelines (Richards 2015). The interpretation of variants is dependent on the clinical context. Interpretations are based on current scientific knowledge and are subject to change. According to the CCMG recommendations (Boycott 2015), variants that are unrelated to the primary indication for referral are not intentionally searched. However, such variants could be incidentally identified during the analysis process. Incidental findings are reported, if variants are interpreted as pathogenic or likely pathogenic, and patient has consented to return an incidental findings report.

Days/times performed

Availability

  • Specimens accepted Monday to Friday, 8:00 a.m. to 5:00 p.m. at the RUH Genomics Laboratory

Maximum laboratory time

Result reporting

  • Turnaround time: 6-8 weeks

Specimen retention time

  • DNA banking specimens are stored and retained at RRPL as their banking policy

Other information

Grounds for Rejection:

Last Updated: April 10, 2024