Mater Pathology

Cardiac Gene Panel Testing

Mater Pathology is now offering one of the most comprehensive and clinically focused cardiac genetic tests currently available. It uses the latest ‘massively parallel sequencing’ technology to identify genetic mutations in a panel of genes that are known to cause a range of different cardiac conditions.

The genes included for each condition have been selected on the basis of clinical significance by an expert team of genetic pathologists at Mater Pathology. Our pathologists also provide comprehensive interpretation, reporting and advice to referring clinicians utilising the service. The test is performed under strict quality standards within our molecular genetics laboratory and has been accredited for compliance with the international standard for medical testing (ISO:15189), from the National Association of Testing Authorities (NATA).

  RCPA LogoNATA Logo
Accredited for compliance with NPAAC Standards and ISO 15189
 
Why do genetic testing for cardiac disorders?
Over forty cardiovascular disorders have been recognised to be caused by genetic mutations1.
Additionally, around 50% of cases with sudden cardiac arrest under 35 are related to inherited cardiac conditions2. Identifying a causative mutation may benefit patients by:
  • Allowing other at-risk family members to clarify and manage their risk
  • Informing patient treatment/management
  • Providing a definitive diagnosis/explanation for why the disease has occurred
  • Facilitate reproductive options such as prenatal diagnosis from amniocentesis / chorionic villus sampling (only available through a clinical genetic service).
Why test a ‘panel’ of genes?
The same cardiac condition may be caused by mutations in any of a number of different genes, while conversely, two people with a mutation in the same gene may present with different cardiac conditions. Furthermore, some cardiac conditions are caused by a person having more than one mutation in the same or different genes3. Panel testing allows all possibilities to be covered simultaneously. Massively parallel sequencing technology allows large panels of genes of interest to be sequenced simultaneously, significantly reducing the overall cost and time taken to complete such testing. Importantly, the gene panels have been specifically designed to reduce the likelihood of generating ambiguous results by ensuring that only genes that are known to be associated with the presenting phenotype are analysed.
 
Who should be tested?
The probability of identifying a disease causing genetic mutation is higher in patients who have a confirmed clinical diagnosis, therefore testing should initially be performed on a family member who is clinically affected. If a disease causing mutation is identified in that individual, other family members may then access testing to see if they too carry the same mutation. Prenatal testing may also be available through our laboratory for pathogenic variants if required.
 
Limitations of the test
This assay will only assess sequence variants in the coding regions of the genes in the appropriate subpanel, with >99% of targeted bases sequenced at >25X read depth. Deletion/duplication analysis can be performed for some genes. Please contact the laboratory for further information if required.
 
Accredited for compliance with NPAAC Standards and ISO 15189
 
Mater Cardiac Panels

% of clinical cases where a genetic mutation is identified

Cardiomyopathy Panels
Comprehensive Cardiomyopathy Panel (all cardiomyopathy subpanels below = 91 genes) (See below)
Hypertrophic Cardiomyopathy Subpanel (52 genes)
ACTC1, ACTN2, ANKRD1, BAG3, CALR3, CAV3, CBL, COX15, CSRP3, DES, EMD, FHL1, FXN,
GAA, GLA, HRAS, JPH2, KRAS, LAMP2, LDB3, LMNA, MAP2K1, MAP2K2, MIB1, MYBPC3, MYH6,
MYH7, MYL2, MYL3, MYLK2, MYOZ2, MYPN, NEXN, NRAS, PLN, PRKAG2, PRKAR1A, PTPN11,
RAF1, RYR2, SCO2, SDHA, SHOC2, SLC25A4, SOS1, TCAP, TNNC1, TNNI3, TNNT2, TPM1, TTR, VCL
65-75% of familial
HCM
Dilated Cardiomyopathy Subpanel (61 genes)
ABCC9, ACTC1, ACTN2, ALMS1, ANKRD1, BAG3, CAV3, CRYAB, CSRP3, DES, DMD, DNAJC19,
DOLK, DSC2, DSG2, DSP, EMD, EYA4, FHL1, FKRP, FKTN, GAA, GATAD1, HADHA, HFE, ILK,
LAMA2, LAMA4, LAMP2, LDB3, LMNA, MIB1, MYBPC3, MYH6, MYH7, MYPN, NEXN, PDLIM3,
PKP2, PLN, PRDM16, RAF1, RBM20, RYR1, SCN5A, SDHA, SEPN1, SGCB, SGCD, SGCG, TAZ,
TBX20, TCAP, TMPO, TNNC1, TNNI3, TNNT2, TPM1, TTN, TXNRD2, VCL
35-50% of familial
DCM
Arrhythmogenic Cardiomyopathy Subpanel (11 genes)
DES, DSC2, DSG2, DSP, JUP, PKP2, PLN, RYR2, TGFB3, TMEM43, TTN
30-40%
Non-compaction Cardiomyopathy Subpanel (15 genes)
ACTC1, CASQ2, DNAJC19, DTNA, HCN4, LDB3, LMNA, MIB1, MYBPC3, MYH7, PRDM16, TAZ,
TNNT2, TPM1, VCL
30%
Arrhythmia Panels
QT Abnormalities Subpanel (17 genes)
AKAP9, ANK2, CACNA1C, CACNA2D1, CACNB2, CALM1, CAV3, KCNE1, KCNE2, KCNH2,
KCNJ2, KCNJ5, KCNQ1, SCN4B, SCN5A, SNTA1, TRDN
70-80% of familial
Long QT, 15-20% of
familial Short QT
Brugada Syndrome Subpanel (14 genes)
CACNA1C, CACNA2D1, CACNB2, GPD1L, HCN4, KCND3, KCNE3, KCNH2, KCNJ8, SCN1B,
SCN2B, SCN3B, SCN5A, TRPM4
25-40% of Brugada
Syndrome
Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) Subpanel (8 genes)
ANK2, CALM1, CASQ2, KCNJ2, KCNQ1, RYR2, SCN5A, TRDN
60-70% of familial
CPVT
Familial Atrial Fibrillation Subpanel (21 genes)
ABCC9, GJA5, HCN4, KCNA5, KCND3, KCNE1, KCNE2, KCNH2, KCNJ2, KCNJ5, KCNJ8, KCNQ1,
LMNA, NKX2-5, NPPA, RYR2, SCN1B, SCN2B, SCN3B, SCN4B, SCN5A
(Too rare to estimate)
Other Panels
Dyslipidaemia Panel (11 genes)
ABCG5, ABCG8, APOB, APOC2, APOE, GPIHBP1, LDLR, LDLRAP1, LMF1, LPL, PCSK9
70-80% of Familial
Hypercholesterolaemia
Aortopathy Panel (16 genes)
ACTA2, CBS, COL3A1, ELN, FBN1, FBN2, LTBP2, MYH11, MYLK, NOTCH1, SLC2A10, SMAD3,
SMAD4, TGFB2, TGFBR1, TGFBR2
70-80% of Marfan,
15-20% of TAAD,
85-90% of Loeys-
Dietz, 90-95% of
Ehlers-Danlos Type IV

Important Service Details:

Request / Payment / Consent Form:   Forms available for download below.  All forms must be completed and accompany the sample being sent to the laboratory.  There is currently no Medicare rebate for this test in Australia. 

Sample required:  9ml EDTA -whole blood OR 5μg genomic DNA

Turnaround time:  8 - 10 weeks

Shipping:  Room Temperature (please contact the laboratory +61 7 3163 8500 for instructions on shipping samples from outside of Australia).

Address:  Mater Pathology, Level 6, Mater Hospital Brisbane, Raymond Terrace, South Brisbane, QLD 4101

Further Technical Information

Enrichment for targeted genes will be  carried out using the Illumina TruSight Cardio Sequencing Panel Kit, followed by massively-parallel sequencing.  While all genes covered in the kit (174 genes) will be sequenced, analysis is restricted to the specific panel of genes requested based on clinical presentation of the patient.  This is done to minimise the time taken to analyse and report results as well as minimise the likelihood of introducing clinically ambiguous results.  Data for all genes is stored and may be reanalysed for a different clinical indication at a later date, if requested.                                                                  

Variant classification used by the laboratory will follow the ACMG best practice guidelines.   Reports will discuss the significance of reported variants in relation to the presenting phenotype, referencing the methodology and literature supporting the conclusions.

MLPA for detection of deletions / duplications

MLPA analysis can be performed on request for some genes.  The test fee is $500 and the turnaround time is 2-4 weeks (assuming the required MLPA test kit is already available in the laboratory).  Please contact the laboratory for further information regarding your gene of interest (Phone:  +61 7 3163 8500).

Cascade testing of family members

Where a pathogenic or likely pathogenic gene change has been identified in an affected family member through our laboratory, testing may be made available to other family members.  This can be accessed by using a standard test request form and the cascade testing patient consent form available here.  The test fee is $200 for a single variant and $50 extra for each additional variant requiring testing.  The turnaround time for results is 2-4 weeks. 

Prenatal Diagnosis

Prenatal testing of amniocentesis or chorionic villi samples is also available where a pathogenic gene change is identified in an affected family member through our laboratory.  

Note: prenatal testing is only available where the sample is being referred by a clinical genetics service following provision of genetic counselling.  The  test fee is $600 and includes assessment for maternal cell contamination.  The turnaround time for results is 1-2 weeks.  Please contact the lab for further information regarding organising such testing in advance of the sample being collected (Phone:  +61 7 3163 8500).

Contact Us

Doctor Liaison
Eammon Mottram pn: +61 466 777 828 email eammon.mottram@mater.org.au
 
Laboratory
Mr Ivan McGown ph: +61 7 3163 6017 email: ivan.mcgown@mater.org.au
 
Genetic Pathologists
Dr James Harraway ph: +61 7 3162 7679 email: james.harraway@mater.org.au