OVERVIEW

KNOW

Hereditary cardiac disorders have a prevalence of 3% in the population. Arrythmogenic diseases are responsible for most cardiac mortality in the young, and congenital heart defects are the most common type of birth defect (1% of all live births). Owing to improved treatment and management options, there are more adults living with congenital heart defects than children. Importantly, deaths from aortic aneurysms may be prevented if individuals at risk are identified and managed. Many cardiac and aortic disorders show overlapping cardiac and non-cardiac symptoms, and genetic testing can help with a differential diagnosis in those cases.
We offer comprehensive and syndrome-specific panels testing for cardiac and aortic disorders.

MANAGE

Genetic information can improve clinical management by determining the right treatment and follow-up plan. It can predict a prognosis and therapy response and, in some cases, identify gene therapy options.

Knowing about a cardiac or aortic disorder allows you to be proactive about your health with management strategies, such as medication, lifestyle changes or surgery.

IMPORTANCE OF GETTING TESTED

If you or a family member has a risk of heart disease, identifying the cause can guide actions to improve the outcome of the disorder. Additionally, family members can be informed and encouraged to also get tested. Our genetic counsellors can provide medical advice.

top-banner

You have a family history of
unexplained cardiac arrest,
cardiac death or sudden aortic events

top-banner

You have a clinical diagnosis
of a heart defect and need
a differential diagnosis

top-banner

You have a child born with
heart defects, such as structural
abnormalities of the heart muscle

top-banner

You have a child with
neurodevelopmental delay who might
have a hereditary heart disorder

top-banner

You need a prophylactic
aortic surgery and want to
determine the right timing

top-banner

You have a hereditary heart disorder
and want to estimate
the risk of a pregnancy

POSSIBLE OUTCOMES OF THE TEST

A molecular genetic diagnostic report outlining the results of the sequencing analysis is provided. Changes in DNA sequences (variants) can be detrimental and lead to the development of a cardiac or aortic disorder, including asymptomatic disorders that develop later in life. We will report pathogenic and likely pathogenic variants as well as variants of unknown significance.
Pathogenic and likely pathogenic variants mean the genetic cause of the observed symptoms has been identified and may help determine the right treatment and management plan.
Variants of unknown significance means there was not enough evidence to classify the variant as either pathogenic or neutral. Annual variant reclassification and testing family members is recommended.
It is important to note that a negative result does not guarantee the absence of a disorder or that the disorder does not have a genetic cause. Genetic testing is an evolving field and may not detect all variants or there may not currently be enough evidence to classify all variants that lead to an inherited disease.

MEDICAL GENETIC COUNSELLING

We provide expert medical genetic counselling as part of a genetic testing journey. Genetic counselling is a process of communication that supports patients and their relatives before and after genetic testing. It is educational, impartial and nondirective. Prior to any genetic test, genetic counsellors will obtain a detailed family history, explain the method of testing that will be used, its risks and benefits, the limitations of the diagnosis and the implications of making a genetic diagnosis (Elliott and Friedman, 2018, Nat Rev Genet 19:735).

Upon receiving the genetic test results, genetic counselling can help the specialist physician and the patient to interpret them. They can be advised of the consequences of the results including the probability of developing the genetic disorder or passing it on to children, as well as ways to prevent, avoid or reduce these risks (Yang and Kim, 2018, Ann Lab Med 38:291). Our goal of counselling is to provide the patient with greater knowledge and thus, a better understanding of the results and the ability to make a more informed decision.

OUR TESTS

ARRYTHMIAS

• Comprehensive Arrythmias & Cardiomyopathies
• Brugada Syndrome
• Catecholaminergic Polymorphic Ventricular Tachycardia
• Short QT Syndrome
• Long QT Syndrome

CARDIOMYOPATHIES

• Arrythmogenic Right Ventricular Cardiomyopathy
• Dilated Cardiomyopathy
• Hypertrophic Cardiomyopathy
• Restrictive Cardiomyopathy
• Left Ventricular/Noncompaction Cardiomyopathy

CONGENITAL HEART DEFECTS

• Comprehensive Congenital Heart Defects
• Alagille Syndrome
• RASopathies With Heart Defects
• Syndromic Congenital Heart Defects
• Isolated Congenital Heart Defects
• Heterotaxy

AORTIC DISORDERS

• Comprehensive Aortic Disorders
• Ehlers-Danlos Syndrome
• Marfan Syndrome
• Marfan-Like Disorders

x

ACCEPTED MATERIAL

1 ml EDTA Blood

TURNAROUND TIME

15-25 working days

TECHNOLOGY

DNA is isolated and next generation sequencing is performed on all coding exons and conserved intronic regions. Single base pair changes, small deletions and duplications and copy number variants (CNV) are identified. Sequencing runs result in a Quality Score of >30 (accuracy >99.9%) in at least 75% of all bases with a coverage of >20-fold. CNV detection sensitivity is 76.99% and precision is 62.59% (with GC limitation between 0.4 and 0.6 per target sensitivity is 77.04% and precision is 84.10%). Variant classification is performed following ACMG guidelines (Richards et al. 2015, Genet Med 17:405; Kearney et al. 2011, Genet Med 13:680).

Test Methodology
Sequencing

Next generation
sequencing (Illumina)

Enrichment

Twist Human Core
Exome plus Ref Seq
Spikeln

SNV and CNV data anlaysis

Illumina DRAGEN
Bio-IT Platform

Data Evaluation

VarSeq by
GoldenHelix

Reference Genome

hg38, NCBI GR38

Quality Criteria

>30 (precision >99,9%)
in min. 75% of bases

SNV detection sensitivity

99.92-99.93%; confirmation of reported SNV with Sanger
sequencing, data analysis with
SeqPilot

Classification of variants

Richards et al. 2015, Genet Med
17:405; Ellard et al. “ACGS Best
Practice Guidelines for Variant
Classification 2020″

in silico algorithms

MaxEntScan,
SpliceSiteFinder-like,
REVEL

Databases

HGMD Professional
release, ClinVar,
gnomAD

OUR TESTS

Genes: JAG1, NOTCH2

Genes: ACTA2, BGN, CBS, COL1A1, COL3A1, COL4A5, COL5A1, COL5A2, EFEMP2, ELN, EMILIN1, FBLN5, FBN1, FBN2, FLNA, FOXE3, GATA5, LOX, LTBP3, MAT2A, MFAP5, MYH11, MYLK, NOTCH1, PLOD1, PRKG1, ROBO4, SKI, SLC2A10, SMAD2, SMAD3, SMAD4, SMAD6, TGFB2, TGFB3, TGFBR1, TGFBR2

Genes: ABCC9, ACTC1, ACTN2, ANKRD1, BAG3, CACNA1C, CACNA2D1, CACNB2, CALM1, CALM2, CALM3, CALR3, CASQ2, CAV3, CRYAB, CSRP3, DES, DMD, DSC2, DSG2, DSP, FHL1, FKTN, FLNC, GLA, GPD1L, HCN4, ILK, JPH2, JUP, KCND3, KCNE1, KCNE2, KCNE3, KCNE5, KCNH2, KCNJ2, KCNJ8, KCNQ1, LAMA4, LAMP2, LDB3, LMNA, MYBPC3, MYH6, MYH7, MYL2, MYL3, MYLK2, MYOZ2, MYPN, NEBL, NEXN, PKP2, PLN, PRDM16, PRKAG2, RAF1, RANGRF, RBM20, RYR2, SCN10A, SCN1B, SCN2B, SCN3B, SCN5A, SGCD, TAZ, TCAP, TECRL, TGFB3, TMEM43, TNNC1, TNNI3, TNNT2, TPM1, TRDN, TRPM4, TTN, VCL

Genes: DSC2, DSG2, DSP, JUP, LMNA, PKP2, TGFB3, TMEM43

Genes: CACNA1C, CACNB2, GPD1L, HCN4, KCNE3, SCN1B, SCN3B, SCN5A, TRPM4

Genes: CALM1, CALM2, CALM3, CASQ2, KCNJ2, RYR2, TECRL, TRDN

Genes: ACTC1, ACVR2B, ADAMTS10, ARHGAP31, BMPR2, BRAF, CBL, CFAP53, CHD7, CITED2, CREBBP, CRELD1, DNAH11, DNAH5, DNAI1, DOCK6, DTNA, EHMT1, ELN, EOGT, EP300, EVC, EVC2, FBN1, FBN2, FLNA, FOXC1, FOXH1, FOXP1, GATA4, GATA5, GATA6, GDF1, GJA1, GPC3, HRAS, JAG1, KDM6A, KMT2D, KRAS, LEFTY2, LZTR1, MAP2K1, MAP2K2, MED12, MED13L, MGP, MMP21, MRAS, MYH11, MYH6, NF1, NIPBL, NKX2-5, NKX2-6, NODAL, NOTCH1, NOTCH2, NPHP4, NR2F2, NRAS, NSD1, PITX2, PKD1L1, PPP1CB, PTPN11, RAF1, RBM10, RBPJ, RIT1, RRAS, SALL1, SALL4, SEMA3E, SHOC2, SMAD6, SOS1, SOS2, SPRED1, TAB2, TBX1, TBX20, TBX3, TBX5, TFAP2B, TGFBR1, TGFBR2, TLL1, ZEB2, ZFPM2, ZIC3

Genes: ABCC9, ACADVL, ACTC1, ACTN2, ALMS1, ANKRD1, BAG3, CAV3, CHRM2, CPT2, CRYAB, CSRP3, CTF1, DES, DMD, DNAJC19, DOLK, DSC2, DSG2, DSP, EMD, EYA4, FHL2, FLNC, FKRP, FKTN, GATA4, GATA6, GATAD1, ILK, JUP, LAMA4, LAMP2, LDB3, LMNA, MYBPC3, MYH6, MYH7, MYPN, NEBL, NEXN, NKX2-5, NPPA, PKP2, PLN, PDLIM5, RAF1, RBM20, RYR2, SCN5A, SDHA, SGCD, SLC22A5, TAZ, TCAP, TMEM43, TMEM70, TMPO, TNNC1, TNNI3, TNNT2, TPM1, TTN, TTR, TXNRD2, VCL,

Genes: ADAMTS2, AEBP1, B3GALT6, B4GALT7, C1R, C1S, CHST14, COL12A1, COL1A1, COL1A2, COL3A1, COL5A1, COL5A2, COL6A1, COL6A2, COL6A3, DSE, EMILIN1, FKBP14, FLNA, PHYKPL, PIEZO2, PLOD1, PLOD3, PRDM5, SLC2A10, SLC39A13, TNXB, ZNF469

Genes: CRELD1, DNAI1, DNAH5, DNAH11, GDF1

Genes: ABCC9, ACADVL, ACTC1, ACTN2, AGL, ALMS1, ANKRD1, BAG3, BRAF, CACNA1C, CAV3, CALR3, CBL, CHRM2, CPT2, CSRP3, CTF1, DES, ELAC2, FHL1, FHL2, FLNC, GAA, GATA4, GLA, HRAS, JPH2, KRAS, LAMP2, LDB3, MAP2K1, MAP2K2, MTO1, MYBPC3, MYH6, MYH7, MYL2, MYL3, MYLK2, MYOM1, MYOZ2, MYPN, NEXN, NF1, PLN, PDLIM5, PRKAG2, PTPN11, RAF1, RASA1, SHOC2, SOS1, SPRED1, TCAP, TNNC1, TNNI3, TNNT2, TPM1, TTR, VCL

Genes: ACTC1, BMPR2, CITED2, DTNA, ELN, FOXH1, FOXP1, GATA4, GATA5, GATA6, GJA1, MED13L, MYH6, NKX2-5, NKX2-6, NR2F2, SMAD6, TAB2, TBX1, TBX20, TLL1, ZFPM2

Genes: ACTC1, CASQ2, HCN4, LDB3, MYBPC3, MYH7, PRDM16, TAZ, TNNT2, TPM1

Genes: CACNA1C, CALM1, CALM2, CALM3, KCNE1, KCNE2, KCNH2, KCNJ2, KCNQ1, SCN5A, TRDN

Genes: FBN1, TGFBR1, TGFBR2

Genes: ADAMTS10, ADAMTS17, ADAMTSL2, ADAMTSL4, FBN1, FBN2, LTBP2, LTBP3, MED12, SKI, UPF3B, ZDHHC9

Genes: BRAF, CBL, HRAS, KRAS, LZTR1, MAP2K1, MAP2K2, MRAS, NRAS, PPP1CB, PTPN11, RAF1, RIT1, SHOC2, SOS1, SOS2

Genes: DES, FLNC, MYBPC3, MYH7, TNNI3, TNNT2

Genes: CACNA1C, CACNA2D1, CACNB2, KCNH2, KCNJ2, KCNQ1

Genes: ADAMTS10, ARHGAP31, CHD7, CREBBP, DOCK6, EHMT1, EOGT, EP300, EVC, EVC2, FBN1, FBN2, FLNA, FOXC1, GPC3, JAG1, KDM6A, KMT2D, MED12, MGP, MYH11, NIPBL, NOTCH1, NOTCH2, NSD1, PITX2, RBM10, RBPJ, SALL1, SALL4, SEMA3E, TBX3, TBX5, TFAP2B, TGFBR1, TGFBR2, ZEB2

OUR NETWORK