Investigation
Cardiac Genetic Testing
A single blood test can identify a gene variant that explains an inherited heart condition — and, through cascade testing of relatives, protect an entire family. Understanding what the test can and cannot tell you is essential before proceeding.
Overview
What Is Cardiac Genetic Testing?
Cardiac genetic testing analyses a patient's DNA — obtained from a simple blood sample — for variants in genes known to cause inherited heart conditions. Modern panels examine 50 to over 100 genes simultaneously using next-generation sequencing, returning a result within four to eight weeks.
Testing is not appropriate for every patient with a heart condition. It is most useful where the clinical picture suggests an inherited cause — a family history of the condition, an unexpectedly young age of onset, or a pattern on echocardiography or MRI consistent with a genetic cardiomyopathy. Where testing is appropriate, it is offered as part of a structured process that includes pre-test discussion and, for significant results, follow-up with a clinical genetics service.
A genetic test returns one of three broad classes of result:
Result Type A
Pathogenic Variant Found
A gene change known to cause the condition is identified. This is actionable — it confirms the diagnosis, may influence management, and enables targeted cascade testing of relatives.
Result Type B
Variant of Uncertain Significance
A change is found but its significance is not yet established. VUS results are neither diagnostic nor reassuring. They may be reclassified as evidence accumulates — requiring ongoing review rather than action.
Result Type C
No Variant Found
No causative variant is identified on the current panel. This does not exclude an inherited condition — the causative gene may not yet be known, or may not be included in the panel. Clinical screening of relatives continues regardless.
A negative genetic test does not mean a condition is not inherited, and does not mean relatives are safe. Clinical surveillance of first-degree relatives should continue even when no variant is identified.
Focus Conditions
Genetic Testing in HCM, DCM & Familial Hypercholesterolaemia
These three conditions represent the most common and most clinically significant inherited cardiac diagnoses encountered in adult cardiology practice — each with a distinct gene architecture and specific clinical utility from testing.
HCM
Hypertrophic Cardiomyopathy
HCM is the most common inherited cardiomyopathy, affecting 1 in 500 people. It is autosomal dominant — each first-degree relative has a 50% chance of inheriting the variant. A pathogenic variant is identified in approximately 40–60% of patients with a confirmed HCM diagnosis. The causative mutations almost exclusively affect genes encoding sarcomere proteins — the mechanical machinery of the cardiac muscle cell.
Key genes (yield: ~40–60%)
Clinical utility
MYBPC3 mutations tend to carry a more benign prognosis; TNNT2 mutations are associated with higher sudden cardiac death risk despite modest wall thickening. Gene-positive / phenotype-negative relatives are enrolled in annual clinical surveillance — echocardiography and ECG — as disease can manifest at any age.
DCM
Dilated Cardiomyopathy
Around 25–35% of DCM is familial. Genetic yield is lower than in HCM — a pathogenic variant is found in approximately 25–35% of patients — but the clinical stakes of specific variants are high. LMNA mutations in particular carry a disproportionate risk of life-threatening arrhythmia, and current guidelines recommend an ICD at a higher ejection fraction threshold than for other DCM causes. Identifying an LMNA variant directly changes management.
Key genes (yield: ~25–35%)
Clinical utility
TTN (titin) truncating variants are the most common, found in 15–20% of DCM. RBM20 and FLNC truncating variants are associated with an arrhythmic phenotype. PLN (phospholamban) p.Arg14del is a founder mutation common in Dutch populations and carries high arrhythmia risk. Peripartum and alcohol-related DCM may carry a genetic predisposition that unmasks under physiological stress.
FH
Familial Hypercholesterolaemia
FH is the most common inherited cardiovascular condition in the UK — affecting approximately 1 in 250 people, yet estimated to be undiagnosed in over 80% of cases. Autosomal dominant inheritance means half of first-degree relatives are affected. Lifelong untreated LDL elevation causes premature atherosclerosis: coronary disease commonly develops in the 30s and 40s in men, 40s and 50s in women. Early diagnosis and treatment with high-intensity statins, ezetimibe, and PCSK9 inhibitors dramatically reduces this risk.
Key genes (yield: ~60–80%)
Clinical utility
LDLR mutations account for ~85% of genotype-positive FH. APOB (receptor-binding domain) and gain-of-function PCSK9 variants make up most of the remainder. Homozygous FH (two pathogenic variants, 1 in 300,000) causes extremely high LDL and aggressive childhood coronary disease — requiring LDL apheresis or novel agents such as lomitapide. Genetic confirmation enables the NHS FH cascade testing programme to reach untested relatives systematically.
The Process
The Testing Pathway
Genetic testing in cardiology follows a structured pathway. No test is ordered and no result delivered in isolation — each step involves clinical judgement and, where significant, specialist genetics input.
1
Clinical Assessment
Dr Nijjer reviews the clinical picture, imaging, family history, and ECG to determine whether genetic testing is appropriate and likely to be informative.
2
Pre-Test Discussion
A detailed conversation covering what the test can and cannot establish, the possible result categories, implications for relatives, and the patient's right to decline. This is not a formality — it is an integral clinical step.
3
Blood Sample
A standard venous blood sample — or in some services, a saliva swab — sent to an accredited NHS or private genomics laboratory for next-generation sequencing panel analysis.
4
4–8 Weeks
Laboratory analysis and clinical interpretation by a multi-disciplinary genomics team, including clinical scientists, bioinformaticians, and clinical geneticists.
5
Results Appointment
Results are discussed face-to-face, never by letter alone for significant findings. A positive result triggers cascade testing planning for first-degree relatives. A VUS or negative result is explained in context.
For complex results — particularly in young patients, those with multiple variants, or those with a VUS — Dr Nijjer arranges a joint review with the NHS clinical genetics service or a specialist inherited cardiac conditions (ICC) multidisciplinary team.
What a Positive Result Means
Implications of Genetic Testing
A positive result is not simply a label — it carries a cascade of clinical, familial, and sometimes practical consequences that should be considered before testing begins.
- Management may change Certain variants alter thresholds for intervention — LMNA mutation in DCM triggers earlier ICD consideration; TNNT2 in HCM heightens vigilance for sudden death risk even with modest wall thickening; confirmed FH justifies high-intensity statin therapy from the point of diagnosis rather than waiting for cardiovascular events.
- Cascade testing of relatives Each first-degree relative (parent, sibling, child) has a 50% probability of carrying the same variant. Targeted single-variant testing is quick, cheap, and definitive. Those who test negative are discharged from cardiac surveillance with certainty; those who test positive enter a monitoring programme — often detecting disease before any symptoms develop.
- Children and predictive testing Predictive genetic testing for adult-onset conditions is generally deferred until age 16–18, when an individual can give their own informed consent. Earlier testing may be appropriate where the condition carries childhood-onset risk — for example, some ARVC variants — and is decided jointly with a clinical genetics team.
- Life insurance In the UK, the moratorium on predictive genetic test results means insurers cannot ask about or use a predictive genetic test result when offering life insurance up to £500,000. However, an existing clinical diagnosis of a heart condition — regardless of how it was identified — can and will be disclosed. Patients should seek independent financial advice if this is a concern before deciding to test.
- Variants of uncertain significance A VUS requires careful handling. It should not be treated as a positive or a negative result — it is simply unknown. It can cause significant patient anxiety if not explained properly. Patients should be made aware that VUS reclassification (to benign or pathogenic) occurs as evidence accumulates, and that re-contact by the genetics service may follow in future years.
Cascade Testing in Practice
How a Family Gets Screened
Once a pathogenic variant is identified in the index patient — the first family member to be diagnosed — a cascade testing letter is prepared for that patient to share with relatives. Relatives contact their own GP for referral, or in some regions can self-refer to an inherited cardiac conditions clinic.
Relatives who test gene-positive but show no structural abnormality on echocardiography (gene-positive / phenotype-negative) are not discharged. They are enrolled in annual or biennial clinical review — echocardiography, ECG, and clinical assessment — because the condition may manifest at any age, and the surveillance window is the opportunity to intervene early.
For FH, the NHS England Familial Hypercholesterolaemia programme coordinates cascade testing nationally, using a software tool (FAMCAT) to map affected family members and track who has and has not been tested — a systematic approach that has identified tens of thousands of previously undiagnosed individuals.
The most powerful argument for genetic testing is not what it tells the individual patient — it is what it enables for the whole family. A single positive result can prompt the identification and treatment of multiple at-risk relatives who would otherwise have had no reason to attend a cardiologist.
Consent
Consenting to Genetic Testing
Consent for cardiac genetic testing goes beyond a signature. It requires a clear understanding of what the test may reveal, for whom, and with what consequences — none of which can be undone once a result is known.
Related Conditions & Tests
Questions About an Inherited Heart Condition?
If you have a family history of cardiomyopathy, sudden cardiac death, or very high cholesterol, Dr Nijjer can assess whether genetic testing is appropriate and guide you through the process from start to finish.