*Source: https://www.years.co/en/wgs-vs-wes* Method comparison # Fifty times more data. Not fifty times more insight. Exome sequencing reads one to two per cent of the genome and finds the majority of clinically interpretable variants within it. Full sequencing reads everything. Where the difference genuinely counts, and where it only raises the data volume. Free intro call Book an appointment - WES is the clinical standard - WGS for defined questions - YEARS Ultimate: both - Medical interpretation included The short answer ## WGS or WES — what you need to know Exome sequencing is the medically validated standard method; full sequencing is the escalation for defined questions. The exome reads the protein-coding regions, around one to two per cent of the genome. That small share contains roughly 85 per cent of the disease-causing variants known today, because a change in the protein has the most direct effect. Whole genome sequencing additionally reads non-coding regions, structural variants, mitochondrial DNA and pharmacogenetics in full breadth. For the typical questions of a preventive examination the exome is sufficient. Full sequencing pays off where structural variants are suspected, where complete pharmacogenetics is wanted, and where a targeted prior investigation left something unexplained. At YEARS the Ultimate programme runs both from one sample. Fundamentals and methods: Genetic analysis explained · Whole genome sequencing in detail Direct comparison ## Feature by feature — and where the standard sits. All figures refer to clinical sequencing at coverage customary for the question at hand, not to research or low-coverage protocols. Feature | WES (exome) | WGS (genome) | Clinical validation WES ahead | The established diagnostic method. In routine care for more than a decade, with defined quality standards | Not a routine method across the board. Used where the exome does not answer the question | Share read Level | Around 1-2 % of the genome, all protein-coding regions — containing roughly 85 % of known disease-causing variants | Around 100 %, coding and non-coding | Typical coverage WES ahead | 100-fold across the coding regions | 30-fold across the entire genome | Point mutations in genes WES ahead | Complete and at three times the depth per position — more reliable for variants on only one of the two chromosomes | Complete, but at lower depth per position | Structural variants WGS ahead | Only to a limited extent, breakpoints usually sit between exons | Reliably, because the regions between exons are read | Regulatory variants Level | Not captured | Captured, but rarely interpretable — the interpretation is largely research | Pharmacogenetics WGS ahead | Core variants of the most important enzymes | Complete, including variants in intronic regions | Variants of uncertain significance WES ahead | Fewer, because less is read | Considerably more, with correspondingly more curation work | Raw data volume WES ahead | A few gigabytes | Roughly 90-120 GB uncompressed | At YEARS Level | Standard in the Ultimate programme | Standard in the Ultimate programme | Clinical validation WES ahead WES (exome) The established diagnostic method. In routine care for more than a decade, with defined quality standards WGS (genome) Not a routine method across the board. Used where the exome does not answer the question Share read Level WES (exome) Around 1-2 % of the genome, all protein-coding regions — containing roughly 85 % of known disease-causing variants WGS (genome) Around 100 %, coding and non-coding Typical coverage WES ahead WES (exome) 100-fold across the coding regions WGS (genome) 30-fold across the entire genome Point mutations in genes WES ahead WES (exome) Complete and at three times the depth per position — more reliable for variants on only one of the two chromosomes WGS (genome) Complete, but at lower depth per position Structural variants WGS ahead WES (exome) Only to a limited extent, breakpoints usually sit between exons WGS (genome) Reliably, because the regions between exons are read Regulatory variants Level WES (exome) Not captured WGS (genome) Captured, but rarely interpretable — the interpretation is largely research Pharmacogenetics WGS ahead WES (exome) Core variants of the most important enzymes WGS (genome) Complete, including variants in intronic regions Variants of uncertain significance WES ahead WES (exome) Fewer, because less is read WGS (genome) Considerably more, with correspondingly more curation work Raw data volume WES ahead WES (exome) A few gigabytes WGS (genome) Roughly 90-120 GB uncompressed At YEARS Level WES (exome) Standard in the Ultimate programme WGS (genome) Standard in the Ultimate programme The balance is not accidental: the exome is the medically validated standard method, and full sequencing is the escalation for defined questions. Reading more bases does not automatically make the better examination — it makes more data. The most important entry in this table is therefore the one on variants of uncertain significance. More data produces more findings that cannot be interpreted with present knowledge. Anyone choosing full sequencing should be prepared for that — and should have medical support that names such findings as what they are rather than reinterpreting them into a recommendation. Decision guide ## Four situations, four answers. The choice follows the clinical question. That arises from family history and existing findings, not from a catalogue. ### Early cancer in the family Breast, bowel or prostate cancer in parents or siblings, particularly before the age of 50. The relevant genes, such as BRCA1, BRCA2 and the Lynch genes, are coding. Answer A targeted panel or the exome is sufficient. Full sequencing adds no further finding here. ### Very high cholesterol LDL markedly raised despite a good diet, possibly with heart attacks in the family. Familial hypercholesterolaemia suspected. Answer The exome is sufficient. The genes LDLR, APOB and PCSK9 are coding and fully covered by the exome. ### Panel or exome with no finding A targeted investigation has already run, family history still points to a hereditary cause, and an explanation is missing. Answer WGS. Structural variants and the regions between exons are then the remaining candidates. ### Several medications, unclear tolerance Recurring side effects or absent effect at standard doses, for instance on clopidogrel, SSRIs or statins. Answer For the core variants the exome or a targeted pharmacogenetics panel is enough. Only complete interpretation including structural variants in CYP2D6 needs WGS. At YEARS ## Why we do not put the question. In the Ultimate programme both methods run from the same blood sample. That is not a bonus but a decision that follows from the process. - — After the blood draw the question cannot be reopened. A second run means a new sample, a new waiting period, a new appointment. - — The marginal cost of additional interpretation from one sample is below that of a second sequencing run months later. - — A finding that appears in both methods is more robust than one from a single method — parallel interpretation allows a plausibility check. - — Physician curation by ACMG criteria and counselling before and after the examination are included in the programme price, not optional. Included in YEARS Ultimate at 16,900 euros, together with pharmacogenetics, epigenetics, microbiome, whole-body MRI, liquid biopsy and more than 230 biomarkers. Sequencing cannot be booked on its own, because a genetic finding without blood values, imaging and family history cannot be interpreted meaningfully. Context ## Three sentences that are often wrong. WGS reads 100 % of the genome. Repetitive regions and very GC-rich stretches remain hard to read even at 30-fold coverage. The figure describes the aspiration, not the outcome of every sample. More data means more certainty. More data initially means more variants of uncertain significance. Certainty comes from curation and clinical context, not from base count. An online gene test is a cheap alternative. Those mostly work with an SNP array and only read predefined positions. On top of that, a predictive examination in Germany may only be ordered by a physician. ## Frequently asked questions about WGS and WES What is the difference between WGS and WES? + Exome sequencing, WES for whole exome sequencing, reads only the protein-coding regions of the genome, around one to two per cent. Whole genome sequencing, WGS, reads everything: coding and non-coding regions alike. The point is not the volume of data, though. Those one to two per cent contain roughly 85 per cent of the disease-causing variants known today, because a change in the protein itself has the most direct effect. WGS additionally finds three classes of finding that remain closed to the exome: structural variants, regulatory variants, and complete pharmacogenetic interpretation. Is WGS better than WES? + Not in general, but for particular questions. WGS reads roughly fifty times as many bases, but the share of that which can be interpreted with clinical confidence today does not grow in the same proportion. For the typical questions of a preventive examination, meaning hereditary cancer risk, lipid metabolism, haemochromatosis and core pharmacogenetics, WES delivers the findings. WGS is the better choice where structural variants are suspected, where complete pharmacogenetics is wanted, and where a targeted prior investigation left something unexplained. More data also means more variants of uncertain significance, meaning more findings nobody can interpret. Is WGS more expensive than WES? + Pure sequencing costs have fallen for years, and the price difference between exome and genome is considerably smaller today than five years ago. What drives the cost difference now is not the reading but the interpretation: more data means more bioinformatic compute, more storage and above all more physician curation work, because more variants of uncertain significance have to be assessed. At YEARS the question is commercially defused, because the Ultimate programme runs both methods and the price of 16,900 euros covers the entire programme rather than sequencing as a line item. Which method fits my situation? + The clinical question decides, and that arises from your family history and your existing findings, not from a catalogue. Three examples. Where breast or bowel cancer occurred early in the family, the route runs via a targeted panel or the exome, because the relevant genes are coding. Where you take several medications and tolerance is unclear, complete pharmacogenetic interpretation from WGS delivers more. Where a panel or the exome has already returned no finding and family history still points to a hereditary cause, WGS is the next step. Making exactly this assignment is the content of the pre-test medical consultation. Why does YEARS run both? + Because the question cannot be reopened after the blood draw. If no explanatory finding emerges from the exome, the next step would be full sequencing, and that means a new sample, a new waiting period and a new appointment. The marginal cost of additional interpretation from one sample is lower than that of a second run months later. Parallel interpretation also allows a plausibility check: a finding that appears in both methods is more robust than one from a single method. At YEARS both are part of the Ultimate programme and cannot be booked separately. And what about the cheap gene tests sold online? + Those generally work with an SNP array, not with sequencing. An array tests individual predefined positions in the genome, typically a few hundred thousand to a million. That is fundamentally different from reading: an array only finds what was asked in advance, and cannot see a rare variant at a position it does not query. For polygenic risk scores that is sufficient, for clarifying a familial cancer risk it is not. On top of that comes the legal framework: in Germany a predictive genetic examination may only be ordered by a physician, with genetic counselling before and after the test. ## Also of interest Genetic analysis Panel, array, exome and genome explained Whole genome sequencing Process, report structure and limits of full sequencing Genetic risk factors Which variants actually carry a consequence Medical genetics Berlin Location, physicians and how it works on site ## The question is not which method. It is which question. In a free intro call we clarify which clinical question your family history actually raises — and which method answers it. Free intro call Book an appointment Medical Disclaimer This information is provided for general education and is not a substitute for professional medical advice, diagnosis or treatment. Please discuss findings and individual medical decisions with a qualified physician. Content is reviewed periodically against the current state of scientific evidence.