How to compare genomic tests, from the laboratory to the report

Start with what the test is built to answer

Every genomic test reads a defined part of your DNA and reports a defined part of what it reads. UK guidance expects the scope and limits of a test, meaning what will and will not be tested for and communicated, to be explained before testing [1]. Two products can both be called a genome test and still report very different numbers of genes.

A gene panel reads a chosen list of genes, while an exome or a whole genome reads far more of your DNA. Which suits you depends on the question you are asking, and a narrow question is often best answered by a narrow test.

Depth and coverage

Depth is how many times each position is read, and coverage is how much of the target is read to that depth. Both shape what a test can reliably find, and the depth needed depends on what the analysis is for [2].

A depth figure on its own says little. Ask what share of the target reached that depth and which regions did not, because a gene that falls in a poorly read stretch can be missed whatever the average.

Accreditation, and what it covers

ISO 15189 is the international standard for quality and competence in medical laboratories. In the UK, accreditation to it is assessed by UKAS, which checks the laboratory’s quality management system and that specific activities are performed within the criteria of the standard [3].

Because accreditation applies to specific activities, it is worth asking whether the test you are buying falls within the laboratory’s accredited scope, as well as whether the laboratory is accredited at all [3].

Interpretation, where most of the difference lies

Reading the letters is the first step. Each variant is then classified on a five step scale, from pathogenic through uncertain significance to benign, under standards from the American College of Medical Genetics and Genomics and the Association for Molecular Pathology [4]. In the UK, the Association for Clinical Genomic Science publishes best practice guidelines for variant classification, last updated in 2024 [5].

Interpretation is where consumer and clinical tests most often differ. A clinical laboratory asked to confirm variants reported in consumer raw data found that 40% were false positives, and some variants labelled as raising risk were classed as benign by clinical laboratories [6].

Interpretation also changes with time. In one large dataset, 7.7% of unique variants of uncertain significance were later reclassified, so a good report says how and when it will be reviewed [7].

Questions to compare tests side by side

Put the same questions to every provider and compare the answers in writing.

• Which genes or regions does the report cover, and is the list named and versioned?
• What depth is the sequencing, and what share of the target reaches it?
• Is the laboratory accredited to ISO 15189, and is this test within its accredited scope?
• Which standards are used to classify variants?
• Are uncertain variants reported, and who explains them?
• Is a positive result confirmed before it changes your care?
• Who reads the result with you, and what happens if something is found?
• Is the report reviewed as evidence changes, and can you download your raw data?

Who may not need a broad test, and the risks

If a relative already carries a known variant, a targeted test for that variant usually gives a cleaner answer. If you have symptoms now, a diagnosis comes before any screening test, and if a result would change nothing you do, a broad test adds little beyond reassurance.

The main risks are false reassurance from a narrow test read as complete, and worry from an uncertain result read as a diagnosis. Both are reduced when a doctor explains what was looked at and what was left out.

How The Wellness can help

Our genome options state their scope plainly. The Sentinel reads the 84 genes where a finding changes what a doctor does, and The Vantage around 200 heart and cancer genes with Lp(a) and ApoB. The Legacy reads the whole genome at 30x with over 500 genes reported, and The Legacy Family offers the same for four people. Every sample is read in an accredited laboratory.

A doctor takes you through the result with a genetic counsellor alongside, writes a plan into your record, and the full raw data files are yours. Every option begins with a free call with one of our doctors, who will tell you which test, if any, fits your question.