About Our Reports

Turnaround times

Please refer to the Turnaround Times page.

Report layout and content

Our laboratory reports are designed to accurately, clearly and unambiguously communicate the results of investigations, and to interpret their significance.

The layout and content is guided by standards provided by external accrediting bodies, external quality assessment, by best-practice guidelines and from consultation with users.

Please contact us for advice or to provide feedback on any aspect of our reports.

Nomenclature

The nomenclature used on laboratory reports conforms to the following standards:

• Gene symbols - HUGO Gene Nomenclature Committee; HGNC
• Sequence variants - Human Genome Variation Society; HGVS
• Karyotypes - International System for Human Cytogenetic Nomenclature; ISCN

Dosage changes

If MLPA analysis identifies a single probe deletion, the presence of a ligation site sequence variant is excluded using an independent assay.

The extent of multiple exon dosage changes cannot be fully characterised and may constitute partial alterations of flanking exons.

Interpreting the pathogenicity of genetic variants

Sequence variants that are detected are generally scrutinised using a variety of tools to determine the likelihood of pathogenicity. Currently, most analysis is integrated using Alamut version 2.10 or Alamut Visual Plus 1.3 (Alamut Visual; interactive biosoftware). Analysis includes:

• • Searching for presence in existing variant/mutation databases
  • Literature search
  • Frequency in disease and normal populations
  • In Silico splice-site prediction
  • Conservation analysis for affected amino acids
  • In Silico missence prediction analysis

Our laboratory follows national and international practice to classify sequence variants into one of 5 classes:

• • Class 1 - Certain non-pathogenicity
  • Class 2 - Likely non-pathogenicity
  • Class 3 - Uncertain pathogenicity
  • Class 4 - Likely pathogenicity
  • Class 5 - Certain pathogenicity

Variant classification is carried out accordance with the ACMG standards and guidelines for the interpretation of sequence variants i.e. ACGS best practice guidelines for variant classification, the CanVIG-UK consensus specification for variant classification in cancer susceptibility genes, or gene specific specialist SVI guidance where available.

In the interest of clarity variants not considered to be of clinical utility are omitted from reports. All other variants are reported, and the wording on the reports reflects the pathogenicity class, and may summarise the evidence in this regard. If predictive testing or carrier testing is appropriate, this will be indicated.

The classification of sequence variants is not always straightforward. Sometimes, this is because of paucity of evidence. By contrast, sometimes there is much evidence, but this remains inconclusive or points to a marginal phenotypic effect.

The assessment of a sequence variant is valid at the time of writing the report. We are not able routinely to monitor for additional evidence after reporting. The exception is for variants recurring in subsequent referrals. Occasionally in these cases, increased evidence causes the re-classification of a variant. And rarely, where this is clinically significant (from class 1,2 or 3 to 4 or 5; or vice versa), we will attempt to recontact the referring clinician and offer an amended report.

For any case, we are prepared to offer further clarification regarding the pathogenicity of a variant, as the scope to do this on the report is restricted.