Depth above 300x
The high average number of reads increases the ability to investigate low-frequency variants in the nuclear exome.
High depth exome
When a genetic change is in only part of the cells.
NeoExoma Mosaico uses high-depth sequencing to investigate changes present in a small proportion of cells. Relevant findings undergo specific confirmation.
- Territory
- Nuclear exome
- Depth
- Average above 300x
- Confirmation
- Above 2000x*
- Post-report
- Infinity VUS included
Why depth matters
A mosaic variant may appear as a discrete signal.
In mosaicism, the change appears after fertilization and is not present in all cells. The smaller its proportion in the sample, the greater the challenge in differentiating it from a technical artifact.
Validation above 2000x
Relevant candidates with allele frequency above 5% sroceed to PCR and high-depth resequencing.
The fabric is part of the strategy
When mosaicism is restricted, a clinically affected sample may be more informative than blood or buccal swab.
* Specific confirmation for candidates within the technical criteria of the test. Sensitivity depends on the allelic fraction, region, quality and tissue analyzed.
Clinical indication
When to consider NeoExoma Mosaico?
The hypothesis gains strength when the signals are segmental, asymmetrical, focal or restricted to one tissue.
01
Segmental overgrowth
Macrodactyly, limb difference, focal growth or suspected PROS/PIK3CA spectrum.
02
Vascular malformations
Venous, lymphatic, capillary lesions or mixed conditions with localized distribution.
03
Focal neurology
Cortical malformations, hemimegalencephaly, focal epilepsy or asymmetric findings.
04
Neurocutaneous syndromes
Segmental skin lesions, tuberous sclerosis with a previous negative test or focal forms of Mendelian diseases.
05
VEXAS syndrome
In people with clinical suspicion, the test can contribute to molecular diagnosis by investigating somatic variants in UBA1, according to the sample and technical criteria.
Case-driven sample
The tissue analyzed can define the chance of finding the signal.
A variant restricted to skin, vessel, bone, or brain may be absent or below the limit of detection in blood or buccal swabs. sample collection of affected tissue depends on indication and clinical feasibility.
The test investigates
SNVs and small indels in the nuclear exome.
- Germline and candidate variants in mosaicism in the evaluable coding regions.
- Small insertions and deletions of up to 20 base pairs, according to the technical scope.
- Classification according to applicable ACMG and ClinGen criteria.
Important limits
Not every form of mosaicism is within reach.
- CNVs and mitochondrial genome are not part of the standard NeoExoma Mosaico analysis.
- Non-coding regions, pseudogenes, high homology and repeats may not be adequately evaluated.
- Expansions, inversions and translocations require another methodology.
- A negative blood or buccal swab result does not exclude a variant restricted to the affected tissue.
Post-report follow-up
Science evolves. The interpretation of a variant may also evolve.
All NeoGenomica tests include Infinity VUS for variants of uncertain significance that are reported.
Your result monitored over time
A variant of uncertain significance, or VUS, is a finding for which the available evidence does not yet allow us to conclude whether it is related to the disease. Infinity VUS monitors classification updates even after the report is issued.
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01 · Monitor
Periodically compares reported VUS with new evidence and classifications.
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02 · Review
A material change is forwarded for expert review before any communication.
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03 · Update
When the reclassification is confirmed and applicable to the case, the responsible team is notified and the report can be updated.
Test day
From hypothesis to confirmation.
A high-depth flow that begins with sample choice and ends with clinical interpretation of the findings.
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01
Discussion of the nomination
The mosaicism hypothesis, the affected tissue and the expected VAF guide the strategy.
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02
Sample definition
Blood, mouth swab or affected tissue, as indicated and clinical feasibility.
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03
Sequencing above 300x
The nuclear exome is analyzed in great depth and undergoes quality control.
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04
Confirmation above 2000x
Relevant candidates within the technical criteria are validated by PCR and resequencing.
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05
Clinical report
The result brings together classification, technical limits, sample context and Infinity VUS.
Frequently asked questions
Before defining the sample.
What is mosaicism?+
This is when a variant appears after conception and is only present in part of the cells. Its fraction in the sample may be smaller and require greater depth for investigation.
What is the difference to a conventional exome?+
NeoExoma Mosaico uses average depth above 300x and confirmation protocol above 2000x for candidates within technical criteria, increasing the ability to evaluate low frequency signals.
Which sample should be sent?+
It depends on the hypothesis. Blood or buccal swab may be appropriate when the variant is in these tissues. In localized conditions, the affected tissue may be more informative when its sample collection is indicated and feasible.
Does a negative result rule out mosaicism?+
Not necessarily. The variant may be below the detection limit, outside the analyzed regions or absent in the tested sample. The result must be interpreted along the phenotype and tissue.
Does the test detect CNVs, expansions and structural variants?+
CNVs are not part of the standard analysis. Examination is also not the methodology of choice for expansions, inversions, translocations, or non-coding regions.
Sample and indication
Discuss the case before sample collection.
The hypothesis, the affected tissue and the expected allelic fraction guide the choice of material and the interpretation of the result.
Catalog information
Technical data of NeoExoma Mosaico
Strategy to investigate variants present in a low proportion in the analyzed sample.
- Applications
- Rare and hereditary diseases, Mosaicism
- Accepted samples
- peripheral blood, Mouth swab, Biópsia de tecido affected (preferred), DNA extraído
- Estimated deadline
- Deadline subject to confirmation by the technical team.
- Methodology
- Nuclear exome with average depth above 300x and confirmation above 2000x by PCR and resequencing for candidates in the technical criteria.
- Analytical scope
- SNVs and small indels of up to 20 base pairs in the nuclear exome; relevant candidates with an allelic fraction above 5% sndergo specific confirmation.
- Medical request
- Required
Requirements
Discussão prévia da hipótese, tipo de amostra, fração alélica esperada e viabilidade clínica da amostra.
Limitations
CNVs and mitochondrial genome are not included in the standard analysis. Non-coding regions, pseudogenes, homology, repeats, expansions, inversions and translocations require another method.
