Cardiology and Respiratory

Cardiology and Respiratory testing

The Clinical Genetics and Genomics Laboratory (CGGL) is based at Royal Brompton Hospital site of the Royal Brompton & Harefield NHS Foundation Trust. We offer next-generation sequencing (NGS) based diagnostic genetic testing for families and individuals at risk of inherited cardiac and respiratory conditions. This testing includes bioinformatic copy number analysis down to the single exon level for the majority of genes tested (excluding some pseudogene regions or low coverage exons). We also provide cascade testing for diagnostic, predictive and segregation purposes, using Sanger sequencing, digital-droplet PCR (ddPCR) or MLPA.

We are one of four cardiac and three respiratory specialist test providers in England, testing for all cardiac and respiratory indications in the National Genomic Test Directory.

CGGL is a UKAS-accredited medical laboratory (ISO15189:2012), and there are more details on our schedule of accreditation (Laboratory ID: 9295, UKAS: Search Accredited Organisations). The laboratory participates in all relevant European Molecular Genetics Quality Network (EMQN) and UK National External Quality Assessment Service (GenQA) Quality Assurance schemes.

The lab works with Clinical Geneticists, specialist clinicians, Genetic Counsellors and advanced nursing teams from a wide range of medical specialties, from a wide range of hospitals. This ensures that patients receive professional advice both before testing and after a result has been given.

The laboratory has a strong research interest, with many publications emanating from the results of diagnostic testing and the development of new assays, ensuring that we remain at the forefront of genomic diagnostics.

Next-generation sequencing assays

Next-generation sequencing associated with a range of inherited cardiac and respiratory conditions (see ‘Tests offered’). Gene panels use targeted gene capture and sequencing is undertaken on Illumina MiSeq or NextSeq550 sequencers.

Bioinformatic analysis and reporting

Comprehensive bioinformatic analysis, including copy number variant (CNV) analysis, clinical interpretation and variant confirmation are reported on genes of relevance to the clinical indication. We provide a comprehensive scientific interpretation of variants found in the genes relevant to the indication, according to the latest versions of variant interpretation guidelines (based on the ACMG Variant Interpretation Guidelines, Richards et al Genet Med 2015 17(5):405-24, and disease and gene-specific variations of the guidance) to accurately assess the likelihood of pathogenicity. On completion of the analysis, a report incorporating full clinical interpretation of the variants identified is provided.

Other specific targets

We perform whole gene sequencing, including intronic regions for major genes for certain indications, e.g. MYBPC3 and MYH7 for HCM and CFTR for cystic fibrosis. Our analysis also includes upstream promotor regions where relevant, e.g. CNV analysis and MLPA for FOXF1 testing in order to detect the known pathogenic promoter deletion.

Sensitivity / specificity / limitations

Analytical sensitivity has been estimated to be more than 99.9% for bases covered to a minimum read depth of 20x. Analytical sensitivity for insertions and deletions is lower (>90%). Specificity and precision are verified to be 100%. All bases in exons of core genes are guaranteed to have a minimum of 20x coverage (with some specific exceptions – specified in the appendix of relevant reports).

Targeted variant analysis and familial testing

If a pathogenic or likely pathogenic variant is detected in a family, affected and unaffected relatives of the proband may wish to be tested for the variant. For this, we use Sanger sequencing, or MLPA, or ddPCR, depending on the type of variant. We may also perform family studies to further refine variant interpretation and to determine whether a variant has been inherited, has arisen de novo, or co-segregates with disease in a family.
All requests for familial testing must have a copy of the index patient’s report, or their full details if tested in our laboratory. It is the responsibility of the referring clinician to provide this. For samples received from family members, where the proband was tested elsewhere, optimal DNA is sent to the relevant testing lab. If this is not possible, we can carry out testing in our laboratory. Predictive testing (for unaffected relatives) should only be requested via a Clinical Geneticist or another referring clinician in association with a Clinical Geneticist.

Re-interpretation of variants

As diagnostic genetic testing is a rapidly advancing field, the classification of variants can change as more data becomes available. We review previous reports on a case-by-case basis following a request from a clinician and can provide re-interpretation for both samples previously tested in our laboratory, as well as variants reported elsewhere, for the indications offered by our lab.

Tests offered

NGS Panel Testing for all inherited cardiac and respiratory conditions according to the National Genomic Test Directory.

Cardiology Specialty
R125 Familial thoracic aortic aneurysm (FTAA) (medium panel)*
R127 Long QT syndrome (LQTS) (small panel)
R128 Brugada syndrome (BrS) (SCN5A) (small panel)
R129 Catecholaminergic polymorphic VT (CPVT) (small panel)
R130 Short QT syndrome (small panel)
R131 Hypertrophic cardiomyopathy (HCM) (medium panel)
R132 Dilated/arrhythmogenic cardiomyopathy (DCM/ACM) (medium panel)
R133 Arrhythmogenic right ventricular cardiomyopathy (ARVC) (small panel)
R138 Molecular autopsy (Sudden Cardiac Death) (medium panel)
R135 Paediatric or syndromic cardiomyopathy (large panel)
R136 Primary Lymphoedema (medium panel)
R391 Barth syndrome (TAZ) (small panel)

Respiratory Specialty
R190 Familial Pneumothorax (small panel)
R186 Hereditary Haemorrhagic Telangiectasia (HHT) (small panel)
R184.1 & R184.2 Cystic Fibrosis full gene including introns (CFTR) (small panel)
R189 Respiratory ciliopathies including non-CF bronchiectasis (medium panel including PCD genes and CFTR)
R330 Alveolar capillary dysplasia (FOXF1) (small panel)
R333 Central Congenital Hypoventilation syndrome (PHOX2B ONLY) (small panel)
R191 Αlpha-1-Antitrypsin deficiency (AAT) (SERPINA1) (small panel)
R192 Surfactant deficiency (childhood ILD) (small panel)
R139 Laterality disorders & isomerism (heterotaxy) (medium panel)
R188 Pulmonary Arterial Hypertension (small panel)

Other main tests not currently specified in the National Genomic Test Directory

Cardiac RASopathies/Noonan spectrum disorders (medium panel)

Respiratory     Pulmonary fibrosis, familial (FPF) (medium panel)

Smaller sub-panels for the above tests are available following discussion with the laboratory (eg: Marfan syndrome only under the FTAA panel).

Gene content of panels is according to ‘Green-’ and ‘amber-’ rated genes on the Genomics England PanelApp website. Please also see the Royal Brompton laboratory webpage for specific information about tests offered and panel content.

* small panel: <20 genes;   medium panel: 20-99 genes;   large panel ≥100 genes

Sanger/ddPCR/MLPA-based cascade testing for all cardiac and respiratory conditions according to the National Genomic Test Directory.

R240.1 Diagnostic/confirmatory testing (patient has phenotype consistent with familial disease-causing variant)
R242.1 Predictive/pre-symptomatic testing (no or unknown phenotype; AVAILABLE FOR PATHOGENIC OR LIKELY PATHOGENIC VARIANTS ONLY)
R244.1 Family studies (carrier testing or segregation analysis for variant interpretation)

Sample Identity/Maternal Cell Contamination studies, using PowerPlex HS16 kit

Through medical research new and improved tests, treatments and devices are developed, our understanding of medical conditions is improved and we can work to improve quality of life.

Sample type and requirements

The following sample types are accepted for testing:

  • EDTA Blood (at least 2ml, or at least 1ml for paediatric samples), preferably two tubes. Other anticoagulants will impact on the testing procedure and samples will not be processed. Clotted blood is unsuitable for analysis.
  • Saliva samples, following discussion with laboratory
  • FFPE tissue
  • Pre-extracted DNA samples from any of the above, or other tissues as available

Samples may be sent by Royal Mail or other postal service, and must be packaged according to UN3373.

Specimens should be delivered to the laboratory as soon as possible after they are taken to ensure the quality of the specimen and the success of the testing procedure. If necessary, blood samples can be left at room temperature below 22 °C or refrigerated at 4°C for up to four days without affecting quality.

Please DO NOT FREEZE blood samples.

DNA samples can be transported at room temperature. DNA is stable for one year at room temperature if suspended in a suitable buffer.

If further testing is required on a sample already stored in the laboratory, please request this in writing.

Samples should be packaged so that they maintain patient confidentiality and prevent leakage and/or contamination to couriers and porters.

Diagnostic specimens should be packed in accordance with packaging instructions PI650 and UN3373 regulations. In summary, primary containers must be packed in secondary packaging in such a way that under normal conditions of carriage they cannot break, be punctured or leak their contents into the secondary packaging. Secondary packaging should then be secured in outer packaging with suitable cushioning material.

Outer packaging may consist of paper, fibreboard, plastics or metal. The sample and referral form should be sealed separately in a biohazard bag to prevent contamination of paperwork in the event of leakage. Each package must be clearly and duly marked with a label showing the characters UN3373 and “diagnostic specimen” or “clinical specimen”. For further information please see the national postal regulations.

Where samples are known to pose a specific high risk (eg. HIV, Hepatitis B/C), the nature of the risk must be clearly marked on the referral form. The referral form and specimen container should be clearly labelled (for example, with danger of infection tape) to indicate its high-risk nature. Please contact the laboratory with any queries regarding the appropriateness of sending any potentially high-risk samples.

Samples may be delivered by hospital porter, by hand, by external post (first-class only) and by courier.

SE GLH: Cardiology request form

The following information MUST be provided with any testing referral:

  • Full patient details (minimum: full name, date of birth, NHS number)
  • Full referrer/requesting Consultant details, including report for return of report
  • Clinical details (Clinical diagnosis or clinical phenotype, relevant family history)
  • Test requested clearly indicated

For NGS diagnostic testing: Specific panel must be indicated

For cascade testing: Full details of any previous testing of the proband/index patient (eg: copy of report), and details of where to source a positive control proband must be supplied.

Testing will be delayed if correct details are not supplied.

SE GLH: Record of Discussion form

The Record of Discussion form can be downloaded and used to guide and record the patient’s consent. This should be saved in local patient records and does not need to be sent with the request form.

Acceptance criteria

A minimum of two patient identifiable pieces of information (ie: name and date of birth) must be present on all samples. UNLABELLED SAMPLES WILL BE DISCARDED AND REPEAT SAMPLING WILL BE REQUIRED. 

The quality and quantity of extracted DNA will be affected if samples are collected in incorrect containers, stored at extreme temperatures, or delayed in transit. This may result in the failure of the test. Any specimens which have been delayed in transit may not be suitable for processing and may therefore not be accepted by the laboratory.

Copy number analysis is successful for approximately 90-95% of samples. Some lower quality samples may fail CNV calling.

DNA extracted from solid tissue, saliva or other sources, or using certain manual extraction methods, may not yield the high-quality DNA required for successful NGS. 100 per cent coverage of core genes at 20X is only guaranteed for DNA extracted from EDTA blood.

Turnaround times

We follow ACGS Genetic Laboratory Reporting Time Targets:

  • Predictive testing – 14 calendar days
  • Familial variant testing (non-predictive) – 42 calendar days
  • Next-generation sequencing panels – 84 calendar days, for non-urgent ‘large panel; (>10 genes) tests; 42 calendar days for non-urgent ‘small panel’ (>10 genes) tests, 21 calendar days for urgent tests (selected clinical cases only, please contact the laboratory for discussion prior to requested this).

If unexpected delays occur during the issuing of results, we will keep service users informed of revised turnaround times. 

Lab address and opening hours

Clinical Genetics & Genomics Laboratory
Royal Brompton Hospital
2nd (Ground) Floor, Sydney Wing
Sydney Street
London SW3 6NP

Mon-Fri 8:30-17:30

For clinical advice

If you wish to discuss results or require any clinical advice, please contact the laboratory either by phone (office hours) or by e-mail. We aim to respond to all e-mail queries within one working day.

Key contacts

Laboratory Director: Dr. Deborah Morris-Rosendahl PhD, ErCLG
(Consultant Clinical Scientist)

Senior Clinical Scientist & Deputy Head of Laboratory: Matthew Edwards, MSc, DipRCPath

Lead Bioinformatician: Shibu John, MSc 

Service Manager: Dr. Anna Ferlin PhD

Quality Manager: Maha Younes, MSc

Tel: +44 (0)207 352 8121 ext. 83009 or 83010
Email: /

CGGL Reporting Policy

  1. Clinically-relevant sequence variants and copy number changes are included in the main report.
  2. Any variants interpreted as benign and likely benign during analysis are not reported.
  3. Any variants of uncertain significance detected and not referred to in the main body of the report are listed below the main text. These variants have been reviewed according to ACMG guidelines, and there is currently insufficient evidence to interpret them as either pathogenic, likely pathogenic, likely benign or benign. A further report may be issued if additional evidence for pathogenicity or otherwise becomes available. The information presented on these variants must NOT be used clinically without consultation with the laboratory as to the current classification of the variant.
  4. Some variants of uncertain significance may not be reported depending on their relevance to the given phenotype and the likelihood of their being clinically actionable.
  5. Carrier status for variants associated with rare autosomal recessive disorders, but not apparently relevant to the patients indicated phenotype, will not be reported.
With any Whole Genome Sequencing (WGS) test ordered, a Record of Discussion (RoD) form will also need to be submitted. This document is to record the patient’s consent for genomic testing and their choice on taking part in research. Guidance on the patient choice conversation can be found here
This RoD form will be available for clinicians to download from this webpage. Once completed with the patient, it can be send to the lab with the corresponding test order form and sample.
Tests available to order will be listed in the National Genomic Test Directory. A test order form will soon be made available for clinicians on this webpage to download and complete. This form will include the address of the laboratory that the appropriate sample and completed form needs to be sent to.
Until the new Genomic Laboratory Service goes live, please continue to follow existing test order processes.
Later this year, the online test ordering tool for Whole Genome Sequencing will be integrated into the National Genomics Informatics System (NGIS) and clinicians will be able to search or filter to find a clinical indication, confirm eligibility criteria and start the test request process for their patient.