SportGene

Genetic evaluation of cardiac muscle disease
Hypertrophic Cardiomyopathy, HCM


Intensive sporting activities can trigger HCM in some individuals with genetic mutations

HCMscreening

A more comprehensive evaluation of HCM

Learn more

Did you know that…

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1 in every 500 people has HCM

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HCM is the most common cardiovascular genetic disease

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There is 50% chance of passing it to children (or inheriting it from parents)

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Sudden cardiac death may be the first symptom, in most severe cases

HCM can be a silent disease…

… but there are lifestyle and therapeutically measures to control and prevent HCM major complications.

Why is Hypertrophic Cardiomyopathy (HCM) a problem?

HCM is a genetic disease that presents clinically as unexplained thickening and increased stiffness of the heart, reducing the left ventricle’s ability to fill and consequently pump blood efficiently. In some cases, the electrical conducting system of the heart is also affected. This may cause abnormal heart rates and/or rhythms to develop.

This disease has a high clinical variability, from mild to severe. It has particularly impact in young people or athletes practicing intensive physical exercise, which may contribute to the development of the pathology and trigger sudden cardiac death.

Hypertrophic_obstructive_cardiomyopathy

Foto Npatchett, adapted


SportGene

An evidence-based genetic test for HCM evaluation

The mutations that encompass SportGene are described in medical and scientific literature as associated to serious HCM-related complications.


HCM SportGene is suitable to:

  • Athletes who practice an intensive physical activity and have the typical “athlete’s heart” in the grey zone (LV wall thickness between 13 and 15 mm).

 

  • Family members of a patient who has an HCM-causing mutation(s): asymptomatic individuals with HCM family history, without phenotype, may be at risk of having the disease causing mutation(s)

 

  • Individuals with a family history of sudden death under 45 years old, when its clinical evaluation is doubtful about HCM diagnosis

 

  • HCM patients to allow genetic cascade

 

Why is it targeted for athletes? Click here to find more!


A negative result does not rule out HCM, as it is possible to have a mutation in another gene (or another gene location) not included in the SportGENE. If a subject has a family history of HCM or a strong clinical suspicion of HCM, he must proceed with the analysis of other HCM related genes.

HCM Screening

A more comprehensive HCM genetic test

 

SportGene HCM Screening
Genetic Variants 184  951 (full panel)
Support clinical evaluation icon-small-check  icon-small-check
Identification of genetic cause of HCM  icon-small-check  icon-small-check
Suitable for Screening  icon-small-check  icon-small-check
Genetic alterations for HIGH risk HCM  icon-small-check  icon-small-check
Genetic alterations for LOW risk HCM  icon-small-check

 


ADDITIONAL INFORMATION

SportGene Gene Panel

ACTC1(2), MYBPC3(84), MYH7(51), MYL3(7), TCAP(2), TNNC1(2), TNNI3(14), TNNT2(17), TPM1(5)

HCMScreening Gene Panel

ACTA1(1), ACTC1(14), ACTN2(4), ANKRD1(3), BRAF(1), CALM3(1), CALR3(2), CASQ2(1), CAV3(1) , COA5(1), COX15(2), CSRP3(11) DES(1), FHL1(3), FHOD3(1), FXN(1), GLA(1), JPH2(4), KLF10(6), MAP2K1(1), MAP2K2(1), MRPL3(1), MTO1(2), MYBPC3(367), MYH6(3), MYH7(309), MYL2(15), MYL3(12), MYLK2(2), MYO6(1), MYOM1(1), MYOZ2(2), MYPN(8), NDUFAF1(2), NDUFV2(1), NEXN(2), OBSCN(1), PDLIM3(1), PLN(7), PRKAG2(7), RAF1(1), SLC25A3(1), SLC25A4(2), SOS1(2), SRI(1), TCAP(6), TNNC1(7), TNNI3(45), TNNT2(55), TPM1(16), TRIM63(3), TTN(6), VCL(1)

Benefits of genetic testing for HCM

ASYMPTOMATIC INDIVIDUALS *


1. Surveillance.
Cardiologists and medical geneticists can advise on lifestyles and on the precautions to be taken, before and/or after HCM development

2. Personalised.
Supports clinical diagnosis estimating individualised HCM risk

3. Safe Sport Practice.
Provides guidance about sport intensity accordingly to the clinical and genetic condition.

* but with relatives with HCM / with family history of HCM / with an identified disease causing mutation

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WITH DISEASE SYMPTOMS

 

1. Personalised.
SportGene supports medical geneticists and cardiologists in diagnosis  by identifying the specific mutation(s) causing the pathology.

2. Effective.
Cardiologists differentiate HCM from the non-pathological “athlete’s heart” when there are still doubts on the final diagnosis.

3. Family extensive.
Being a hereditary disease, genetic testing may also estimate family risk for the family relatives who inherited the genetic mutation(s) associated with the disease.



SportGene Testimonials

In the case of identification of a mutation associated with a severe diagnosis or prognosis of HCM, the doctor may advise an implantable cardioverter defibrillator (ICD). ICD monitors and controls abnormal heartbeats, thus preventing sudden cardiac death events.

nuno_cardim

Nuno Cardim, Medical doctor (PhD) on Cardiology; Director of Laboratório de Ecocardiografia at Hosp. da Luz; Member of the European Society of Cardiology

 

Start improving HCM diagnosis today

(Only for registered medical doctors, register here)

Download SportGene Requisition Form: PT | EN

Download HCMscreening Requisition Form: PT | EN


Go back to products  |  Download Product Sheet  |  Need further information? Contact us


HCM SportGene is an evidence-based tool to support the clinical diagnosis and family screening of HCM

The Scientific Background


1. HCM Genetic Context

HCM is the most common genetic disease of the cardiovascular system and has a prevalence of 1:500 in the general population [1,2,4].

HCM has an autosomal dominant transmission pattern and a high clinical and genetic variability [1,4].

The genetic origin: The primary pathophysiological mechanism of HCM is thought to be a deficit in force generation and/or transmission and an inefficient use of energy. These mechanisms are controlled by proteins of the sarcomere, the cardiomyocytes functional unit, affected by HCM specific mutations.

Mutations in the genes listed below are considered responsible for over 80% of known sarcomeric HCM genetic causes:

MYH7 – β-myosin heavy-chain;

MYPBC3 – myosin binding protein C;

TNNT2 – troponin T;

TNNI3 – troponin I;

TPM1 – α-tropomyosin;

MYL2 – regulatory myosin light chain;

MYL3 – essential myosin light chain;

ACTC1 – cardiac actin.

Though individual genotype-phenotype correlations are currently under investigation, the presence of a positive genetic test and the presence of complex genotypes (with double or triple mutations) are emerging as an important issue of adverse outcomes and deleterious prognosis.

2. SportGene and HCM Screening Gene Panels


  SportGene – Study of Molecular Pathologic Markers for HCM

9 Genes (184 Genetic variants)

ACTC1(2), MYBPC3(84), MYH7(51), MYL3(7), TCAP(2), TNNC1(2), TNNI3(14), TNNT2(17), TPM1(5)

HCM SportGene genetic panel developed by HeartGenetics includes the evaluation of high-risk genetic variants associated with HCM development.

Despite genotype-phenotype correlations in HCM are still under intensive research, the selection of these genes and mutations was based on literature descriptions of HCM severe phenotype, early onset and family history of sudden death.


HCM Screening – Genetic Study of HCM

53 Genes (951 Genetic variants)

ACTA1(1), ACTC1(14), ACTN2(4), ANKRD1(3), BRAF(1), CALM3(1), CALR3(2), CASQ2(1), CAV3(1) , COA5(1), COX15(2), CSRP3(11) DES(1), FHL1(3), FHOD3(1), FXN(1), GLA(1), JPH2(4), KLF10(6), MAP2K1(1), MAP2K2(1), MRPL3(1), MTO1(2), MYBPC3(367), MYH6(3), MYH7(309), MYL2(15), MYL3(12), MYLK2(2), MYO6(1), MYOM1(1), MYOZ2(2), MYPN(8), NDUFAF1(2), NDUFV2(1), NEXN(2), OBSCN(1), PDLIM3(1), PLN(7), PRKAG2(7), RAF1(1), SLC25A3(1), SLC25A4(2), SOS1(2), SRI(1), TCAP(6), TNNC1(7), TNNI3(45), TNNT2(55), TPM1(16), TRIM63(3), TTN(6), VCL(1)

HCM Screening includes all genetic variants evaluated in SportGene and adds 767 genetic variants for a complete evaluation of the HCM genetic cause.

HCM Screening gene panel includes 53 genes recognized by the scientific community as associated with HCM.


Note: Before performing the HCM Screening and SportGene all the individuals are informed of the limitations of HCM genotype-phenotype correlations. Moreover, they are informed that are being screened for HCM causing mutations known by the time of the test development. They are also informed that while a positive study confirms a genetic defect, a negative result doesn´t exclude it as it is possible to have a non described disease causing mutation.

3. International Guidelines


ACCORDING TO THE EUROPEAN

SOCIETY OF CARDIOLOGY

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ESC HCM genetic testing recommendations in probands


ESC HCM genetic testing recommendations relatives


ESC HCM genetic testing fluxogram


nuno_cardim Read “A personal view on the 2014 ESC-HCM Guidelines by Dr. Nuno Cardim”

SportGene Testimonials: applications of Genetic test

Medical Case 1

A 16 years old athlete, asymptomatic, without clinical evidence of HCM (by electrocardiogram, bidimensional and stress echocardiograms, cardiac magnetic resonance, Holter) and with familial history of sudden cardiac death (father died of sudden death at 43 y.o., autopsy showed evidence of HCM). Genetic screening for HCM revealed the presence of a MYBPC3 mutation (Arg495Gln) in heterozygosity. It was advised the immediate suspension of sport activity. Two years later, cardiac magnetic resonance showed a 14mm thickening of the interventricular septum.

index  Dra Isabel Gaspar, M.D., Geneticist

Medical Case 2

A 13 y.o. boy, asymptomatic, died of sudden cardiac death. The mother was already diagnosed with HCM and had an implantable cardioverter defibrillator. There was a familial history of sudden cardiac death: uncles and cousins (from the mother side) had died in the second and third decades of life. The proband was followed twice a year by pediatrics cardiology and there was no recorded evidence of HCM (by electrocardiogram, bidimensional echocardiogram, cardiac magnetic resonance, Holter). Autopsy showed evidence of HCM. Molecular autopsy revealed the presence of a MYBPC3 mutation (Glu258Lys) in heterozygosity.

index  Dra Isabel Gaspar, M.D., Geneticist

Medical Case 3

A 19 years old male with family history of HCM (MYBPC3 mutation) and SCD (father with HCM died suddenly at 30 years old,) underwent a cardiology consultation in a HCM centre. He was a professional rugby player (10 hours a week) and wanted to know if he could go on practicing sports. He was asymptomatic and the physical examination unremarkable. The ECG, echocardiography and cardiac magnetic resonance showed “gray zone findings” and the differential diagnosis between athlete’s heart and HCM was not clear. His genetic test was positive for the same MYBPC3 mutation of his family and he was advised to stop competitive sports. One year later, he repeated the imaging tests that showed unequivocal signs of HCM (interventricular septum wall thickness 20mm).

  Dr Nuno Cardim, M.D., Cardiologist

Medical Case 4

Alex is a 18 years old boy with HCM (genetic test with a missense mutation in the MYH7 – β-myosin heavy-chain). Susan, his 13 years old sister is asymptomatic with normal clinical examination, ECG and echocardiogram (she was performing this evaluation every year since she was 11). His genetic test was negative for his brother’s disease causing mutation. She was discharged from follow up with the indication to seek for medical examination only if she developed any new cardiac symptom.

   Dr Nuno Cardim, M.D., Cardiologist

4. How are genetic variants selected

1. Research

Our research is supported by highly cited papers that have been published in the reference journals in the field.

2. Selection

All genetic variants have been validated in reference databases (HGMDP, NCBI-OMIM, NCBI-ClinVar, NCBI-Variation Reporter and Ensemble).

3. Validation 

The knowledge in our databases was approved by internationally recognised medical geneticists and cardiologists.


5. How are SportGene and HCM Screening reports?


HCM reports

1. Simple

Each report include simple and supporting texts explaining the most relevant information to guide the interpretation of test results.

2. Focused

The methodology directly examines the presence or absence of a specific genetic variant associated with the pathology.

3. Rigorous

HCM SportGene and HCM Screening tests have 99% accuracy. All evidence is supported by scientific bibliography and validated by medical experts.


 HeartGenetics reports follow the recommendations from the European Society of Human Genetics [14].

European Society of Human Genetics.

Contact us here for complete genetic test model report

Start improving HCM diagnosis today

(Only for registered medical doctors, register here)

Download SportGene Requisition Form: PT | EN

Download HCM Screening Requisition Form: PT | EN


Go back to products  |  Download Product Sheet  |  Need further information? Contact us

Selected references



[1] Heart Fail Clin. 2010 Apr;6(2):141-59
[2] Cardiovascular Medicine. 2008;5(3):158-168
[3] J Am Coll Cardiol. 2011;58(25):e212-e260
[4] Circulation 2011;123:544-550
[5] J Am Coll Cardiol. 2009;54:201–211.
[6] Eur Heart J. 2010; 31:926–935.
[7] Circ Cardiovasc Genet. 2009; 2:182-190.
[8] Neth Heart J 2007; 15:184-9
[9] Prog Pediatr Cardiol. 2011;31(2):93–98.
[10] Eur J Prev Cardiol. 2013;20(5):889-903
[11] ESC – Eurospace. 2011;13:1077-1109
[12] Eur J Hum Genet. 2014;22(2):160-70
[13] Eur Heart J. 2014 Oct 14;35(39):2733-79
[14] Eur J Hum Genet. 2014. 22(2):160-70.