Whole exome sequencing (WES)
Sequences the protein-coding regions of the genome, where a large proportion of known disease-causing variants are found. Available as proband-only or trio (patient + both parents), which may improve diagnostic yield.
Clinical Area · Rare Disease
Help shorten the diagnostic odyssey with genomic insight
Many patients with rare or undiagnosed disease go years without a molecular explanation. Whole exome and genome sequencing, combined with expert variant interpretation, can offer one of the more comprehensive diagnostic pathways available — often considered after other approaches have been exhausted.
Whole genome sequencing (WGS)
Covers the entire genome including non-coding regions and structural variants. Used when WES has been uninformative or when a non-coding or structural cause is suspected.
Targeted rare disease testing
For specific clinical suspicions: SMA (SMN1/SMN2 MLPA), Fragile X (FMR1 repeat expansion), Sanger-based familial variant confirmation, and other focused assays.
Clinical indications
When to consider rare disease genomic testing
Suspected monogenic disease without a clinical diagnosis despite prior evaluation
Multiple congenital anomalies or a complex phenotype not explained by standard workup
Pediatric neurological deterioration or regression of unknown etiology
Intellectual disability or developmental delay — especially with dysmorphic features
Family history of a suspected hereditary condition — proband-first evaluation
Prior inconclusive testing (targeted panels, karyotype, array) — exome or genome as next step
Available tests
Rare disease tests through AC
3billion
DGS — Proband
Genome sequencing for a proband with suspected rare or undiagnosed genetic disease.
Method: NGS
Specimen: EDTA whole blood
TAT: ~65 days
3billion
DGS — Trio
Trio-based genome sequencing for rare disease evaluation.
Method: NGS
Specimen: EDTA whole blood
TAT: ~65 days
AC Network
Family Test (Sanger)
Targeted familial variant testing using Sanger sequencing.
Method: Sanger
Specimen: EDTA whole blood / amniotic fluid
AC Network
Fragile-X Screening
FMR1 repeat-expansion screening for Fragile X syndrome indications.
Method: Fragment analysis
Specimen: EDTA whole blood
TAT: ~12 days
AC Network
SMA — SMN1/SMN2 del/dup (MLPA)
SMN1/SMN2 dosage analysis for spinal muscular atrophy.
Method: MLPA
Specimen: EDTA whole blood
TAT: 21–30 days
3billion
WES — Proband (3 Billion)
Whole exome sequencing for a proband with suspected rare genetic disease.
Method: NGS
Specimen: EDTA whole blood
TAT: ~30 days
GC Genome
WES — Proband (GC Genome)
Whole exome sequencing through GC Genome for proband-only evaluation.
Method: NGS
Specimen: EDTA whole blood
TAT: ~30 days
GC Genome
WES — Trio (GC Genome)
Trio whole exome sequencing through GC Genome.
Method: NGS
Specimen: EDTA whole blood
TAT: ~30 days
3billion
Whole Genome Sequencing (3 Billion)
Whole genome sequencing for broad rare disease assessment.
Method: NGS
Specimen: EDTA whole blood
TAT: ~30 days
Result interpretation
What whole exome and genome results mean
Results should always be interpreted by a clinical geneticist or genetic counsellor in the context of the patient's phenotype, family history, and prior investigations.
Diagnostic
— Pathogenic or likely pathogenic variant consistent with phenotype
A molecular diagnosis has been identified. This may open options for targeted management, treatment, recurrence-risk counselling, and cascade testing for at-risk family members. The clinical significance of the finding should be reviewed with the ordering physician and, where appropriate, a clinical genetics team.
Variant of uncertain significance (VUS)
— Detected variant with unclear clinical impact
A variant has been detected but its clinical significance has not been established. Management decisions should not be made on the basis of a VUS alone. Classification can change over time as population databases, functional studies, and segregation evidence accumulate. AC recommends discussing VUS findings with a clinical genetics specialist.
Negative
— No pathogenic or likely pathogenic variant detected
No pathogenic or likely pathogenic variant was identified in the genes analyzed. A negative result does not exclude a genetic diagnosis — conditions caused by non-coding variants, large structural rearrangements, deep intronic changes, or genes not yet associated with disease may not be captured by current sequencing approaches.
Secondary / incidental findings
— Variant unrelated to the primary indication
Variants in genes unrelated to the primary clinical question but of established clinical significance may be reported, depending on the laboratory's policy and applicable reporting guidelines (e.g., ACMG secondary findings list). The scope of incidental findings reporting varies by test and should be confirmed before ordering.
Rare disease · clinical detail
Acceptance, limitations & reporting
General guidance to support ordering decisions. Specific thresholds, specimen requirements, and assay availability are confirmed per case with the reference laboratory before testing.
Sample acceptance criteria
- Peripheral blood (or a validated alternative) per the specimen guide; trio testing requires biological parents' samples where indicated.
- Detailed phenotype (e.g., HPO terms) and family history materially improve interpretation; consent appropriate to exome or genome testing.
Assay limitations
- Exome and genome sequencing may not reliably detect repeat expansions, some structural or copy-number variants, deep-intronic variants, or low-level mosaicism; certain regions have reduced coverage.
- A negative or uninformative result does not exclude a genetic cause; periodic reanalysis as knowledge evolves may be informative.
- Variants of uncertain significance are common and require cautious, phenotype-anchored interpretation.
What's reportable
- Pathogenic and likely pathogenic variants relevant to the reported phenotype.
- Secondary or incidental findings only where consented and per the laboratory's policy.
- Trio segregation information and variants of uncertain significance per policy.
Diagnostic yield depends on phenotype, prior testing, and whether trio analysis is performed.
Rare disease · common questions
Rare disease testing — questions clinicians ask
When should I choose whole exome versus whole genome sequencing?
Whole exome sequencing (WES) covers the protein-coding regions where most known disease-causing variants lie and is the usual first-line genomic test. Whole genome sequencing (WGS) adds non-coding and structural coverage and is generally considered when WES is uninformative or a non-coding or structural cause is suspected. Targeted assays (e.g., SMA, Fragile X) are appropriate when the clinical suspicion is specific.
Does trio testing improve the diagnostic yield?
Often, yes. Sequencing the patient with both biological parents (trio) helps establish whether a variant is de novo or inherited and aids interpretation and phasing, which can increase diagnostic yield and reduce uncertain results. Detailed phenotype (e.g., HPO terms) and family history further improve interpretation.
Does a negative result rule out a genetic cause?
No. Exome and genome sequencing may not reliably detect repeat expansions, some structural or copy-number variants, deep-intronic variants, or low-level mosaicism, and some regions have reduced coverage. A negative or uninformative result does not exclude a genetic cause, and periodic reanalysis as knowledge evolves may later be informative.
What is reanalysis, and when is it worthwhile?
Reanalysis re-examines existing sequencing data against updated gene-disease knowledge and variant databases. Because new gene-disease associations are published continually, a case that was uninformative can become diagnostic over time — reanalysis after a suitable interval (or when the phenotype evolves) is a recognised route to a delayed diagnosis without resequencing.
Rare disease
Start with the clinical picture
Share the phenotype, prior testing history, and available specimen. AC can help identify the most appropriate sequencing strategy and navigate the logistics.
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