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 (CNVs) are included in the main report. Reported CNVs are all confirmed by either MLPA or ddPCR.
- We report on variants considered pathogenic, likely pathogenic or of uncertain pathogenicity. Variants considered unlikely to be pathogenic are not generally reported.
- Any variants interpreted as likely benign or benign during this analysis are not reported.
- Any variants of uncertain significance detected and not referred to in the main body of the report, are listed in a table on P.2 of 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).
- Full analysis is only performed on TTN truncating variants. The involvement of TTN missense variants in cardiomyopathy is currently unclear, and our analysis only includes missense or synonymous changes that are predicted to affect splicing.
Interpreting the pathogenicity of genetic variants
Detected sequence variants are assessed and categorised following guidelines produced by the American College of Medical Genetics (ACMG)  and the UK Association of Clinical Genomic Science (ACGS), as well as up-to-date literature on the assessment of variants in specific genes. We use an in-house, UKAS-accredited bioinformatics pipeline that includes a variety of tools and interrogates various international databases, to determine the likelihood of pathogenicity of each variant detected. Preliminary variantreports, on which the final reports are based, are directly generated from our in-house bioinformatics pipeline.
Our laboratory follows national and international guidelines, variants are classified into one of five classes:
- Class one – benign
- Class two – likely benign
- Class three – uncertain pathogenicity
- Class four – likely pathogenic
- Class five – pathogenic
Classifying sequence variants is not always straightforward, as there can be a paucity of evidence available for a particular variant, particularly variants that have not been previously observed. Sometimes the evidence available remains inconclusive or indicates a marginal phenotypic effect. Assessing a sequence variant with regards to its possible association with disease is therefore 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 if and when 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; these are only reported when they are predicted to affect splicing. All variant data remains in the laboratory. Failure to detect a disease-causing variant cannot exclude a diagnosis.
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 be reported. We will not analyse any panels other than those initially requested, without further written consent.
Contacting the laboratory
Referrers are welcome to contact the laboratory with any queries about:
- pre-test advice on appropriate testing
- the interpretation of diagnostic results
- further cascade testing in family members
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 lab complies with our information governance policy to ensure we protect personal information.