Report layout and content
Our laboratory reports are designed to accurately and clearly communicate investigation results, and interpret their significance for patients.
Our layout and content meet standards provided by external accrediting bodies, incorporating external quality assessment, best-practice guidelines and consultation with users.
If you need advice or want to give feedback on any aspects of our reports, you can contact us.
The nomenclature used on laboratory reports conforms to the following standards:
Target regions are defined as coding exons +/-8bps. The A of the translation initiation codon ATG is base 1.
- Clinically-relevant sequence variants and/or copy numbers variants are included in the main report and have been confirmed by Sanger sequencing, MLPA or ddPCR.
- Any variants interpreted as benign during this analysis are not reported.
- Any variants of uncertain significance detected and not referred to in the main report are listed in a table on the report. Variants in this table have been scientifically reviewed, with currently insufficient evidence to interpret them as either pathogenic, likely pathogenic, or likely benign. There may be a need for a further report if extra evidence for pathogenicity or otherwise becomes available. These variants have not been confirmed by a second method, and the information presented must NOT be used clinically without confirmation (please contact the lab if you need confirmatory testing).
- Only full analysis of TTN truncating variants is undertaken. The involvement of TTN missense variants in cardiomyopathy is currently unclear, and our analysis only includes predictions of splicing changes.
Interpreting the pathogenicity of genetic variants
Detected sequence variants that are scrutinised following guidelines produced by the American College of Medical Genetics (ACMG) . We use an in-house validated pipeline including a variety of tools to determine the likelihood of pathogenicity. Analysis is currently integrated into a bespoke in-house bioinformatics pipeline.
Our laboratory follows national and international guidelines to classify sequence variants into one of five classes:
- Class one – benign
- Class two – likely benign
- Class three – uncertain pathogenicity
- Class four – likely pathogenic
- Class five – pathogenic
We report on variants considered pathogenic, likely pathogenic or of uncertain pathogenicity. Variants considered unlikely to be pathogenic are not generally reported.
Classifying sequence variants is not always straightforward, as there can be a paucity of evidence regarding pathogenicity. Sometimes the evidence available remains inconclusive or indicates a marginal phenotypic effect. So assessing a sequence variant with regards to its possible association with disease is valid at the time of reporting. More evidence affecting this assessment may become available after reporting. We will attempt to re-contact the referring clinician and offer an amended report as we are made aware of such information.
Currently, there is insufficient data in the literature or in our cohort to enable us to accurately interpret the clinical significance of synonymous variants, so these are only reported when they affect splicing regions. Similarly, we do not interpret missense variants within the TTN gene. Data on synonymous variants and TTN missense variants stay in the laboratory. If evidence for pathogenicity becomes available, we will then report further.
Failure to detect a disease-causing variant cannot exclude a diagnosis. This is because of genetic heterogeneity and test sensitivity.
If predictive or carrier testing in more family members is appropriate, this will be indicated.
All interpretations are based on family relationships being as stated.
Although bioinformatic analyses are conducted across many genes, the use of disease-specific sub-panels reduces interpretation to the requested sub-panel only. A request for an expanded sub-panel may result in findings not relevant to the initial diagnosis. All variants relevant to the requested test will are reported. We will not analyse any panels other than those initially requested without further written consent.
The hereditary haemochromatosis gene, HFE, is included in the TruSight Cardio kit. As hereditary haemochromatosis is a recessive disorder, only homozygous or compound heterozygous mutations within HFE will be reported. We will not report on haemachromatosis carrier status.
Contacting the laboratory
Clinicians are welcome to contact the laboratory with any queries about:
- the interpretation of reports
- pre-test advice on appropriate testing
- any other enquiries.
We welcome all feedback and suggestions to improve our service. Any complaints are investigated in line with our departmental policy. Please feel free to contact us.
We get in touch with users each year to complete a user survey. This helps us to ensure we are meeting our user's need and improving our service.
The interpretation of results depends on the:
- diagnosis of affected individuals
- identification of samples
- biological relationships of the individuals being correct.
The lab complies with our Trust's information governance policy to ensure we protect personal information.
Ground floor (level 2), Sydney wing, Royal Brompton Hospital, Sydney Street, London, SW3 6NP
Opening hours: Monday to Friday, 9 am - 5 pm
Head of laboratory: Dr Deborah Morris-Rosendahl
Molecular genetic testing request and consent form (pdf, 431KB)