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ExomSure|Dx

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 Condition Description  ExomSure|Dx Result
 Genetic Counselling  Specimen Requirements

 

Condition Description

What is the ExomSure| DX ?

The human exome is the complete coding (exonic) region of the genome. It is estimated to encompass approximately 1-2% of the genome, yet contains approximately 85% of disease-causing pathogenic variants.

Current off-the-shelf exome kits used for clinical exome sequencing covers 92% of the exome. Traditionally, gene discovery has been done in research laboratories; however, now with the ability to sequence nearly the entire coding region of the human genome, it is possible for clinical laboratories to use this information to identify a previously unrecognized cause of disease.

The ExomSure| DX  is the next level in medical exome sequencing offered by Eurofins Clinical Genetics India Pvt. Ltd. (ECGI). The exome sequencing design provides >97% coverage of 22,000 genes, with a mean read depth of 100X. Most of the disease-associated genes are analyzed,having maximum coverage upto 100%  (depth coverage ≥20X) of all exons; which represents twice the number of genes with complete coverage offered by competitors, making it the most comprehensive exome sequencing test available. The exome sequence analysis and interpretation is performed by CLIA-/CAP-certified workflow.

The ExomSure| DX test can be carried out for Proband, Trios and additional family member, which allows clinicians to choose relevant disease associated gene related to  patient’s phenotype.  ECGI is  India’s  first  clinical laboratory to offering ExomSure| DX    test in collaboration with  Emory Genetic Lab (EGI), USA.

Why is my clinician suggesting ExomSure | DX  test?

By sequencing DNA, the clinicians may be able to know the genetic cause for the disease   showing differential diagnostic phenotypes  or your health related conditions. This test is referred  when there is a suspicion of a genetic etiology contributing  to the proband’s manifestations.

Findings of ExomSure | DX

  •   Determine the possible cause of genetic conditions your disease or symptoms.
  •   Determine the risk that you or your family member may develop a disease.
  •   Help to choose the best treatment.

How is the ExomSure | DX performed?

ExomSure | Dx is performed on genomic DNA, isolated from blood, FFPE, saliva and body fluid. The exonic region are enriched using the proprietary technology designed by EGL which has additional coverage of know disease associated genes for better allele frequency. The ExomSure library using Next Generation Sequencing (NextSeq 500 / HiSeq) with 75/150 base pair (bp) pair-end reads having coverage ~100X in the target region. The data is quality filtered and qualified for downstream analysis. the data is mapped on human genome build UCSC hg19 reference sequence. The coding exons and splice junctions of the known protein-coding RefSeq genes are assessed for the depth of coverage and data quality threshold values. The ExomSure analysis will be performed using proprietary bioinformatics pipeline and database developed in collaboration with EGL. If the quality criteria does not meet the standards, then more data will be generated before further interpretation of result.

Further confirmation of all potential positive sequence variants in the patient can be confirmed by gold standard Sanger sequencing method for further verification to ensure proper scientific outcome (Contact ECGI).

Trios / Additional Family Member

Traditionally there are two options when ordering exome sequencing. One can analyze only the affected individual (proband only) or a family trio (typically the affected person and his/her parents). Analyzing trios has shown to increase the diagnostic yield of exome sequencing by providing deeper insight into proband’s findings. Eurofins Clinical Genetics India (ECGI) offers Trios/  additional family members to further increase the clinical efficacy of its exome sequencing. This test allows clinicians to send in an additional child or family member (affected or unaffected) to help sort out findings of unclear significance.

Please consult your doctor or genetic counsellor at ECGI for appropriate test code.

ExomSure|Dx Sequencing Process Flow

  •  DNA isolation from blood or saliva
  •  Library Preparation
  •  Illumina NextSeqTM 500 Sequencing
  •  Sequence Alignment and variant detection
  •  Medical Review
  •  Clinical Report
  •  Counselling

ExomSure|Dx Result and Interpretation:

  •  Positive: A pathogenic variant is identified related to the disease.
  •  Negative: No changes (Pathogenic) in the exomes which are sequenced.
  •  Variant of mutation significance (VUS): A variant is found but the effect is unknown.

Reporting of Results

ECGI’s ExomSure | Dx reports include mandatory disclosures and optional disclosures. Mandatory disclosures for adults and children include:

  • Diagnostic finding related to the patient’s clinical presentation-pathogenic variant(s), likely pathogenic variants(s), and variants(s) of unknown significance in genes interpreted to be responsible for, or contributing to, the patient’s clinical presentation.
  • Diagnostic finding not related to the patient’s clinical presentation will be reported on requested.

Limitations

This ExomSure | Dx sequencing panel covers majority of the exon of genes which are associated with diseases. Nevertheless, some areas of the exome are poorly covered or absent from the data or are unknown. Thus, mutations in those regions may remain unidentified. Furthermore, some types of mutations (such as repeat expansions, copy-number variants, mitochondrial-DNA mutations and areas beyond the exome, including introns and promoters) may not have been detected by this test.   The gene lists associated with diseases are updated regularly, but still may be incomplete due to the continuous identification of novel genes in human disease.

Specimen Requirements

Proband / Trios  / Family Member

Additional Specimen Collection / Handling Instructions Required for this Test

Please send samples of affected individual. It is recommended to also carry out the test for parental samples.

Genetic Counselling

Genetic Counsellors are part of healthcare professional team with background not limited to biology, genetics, and public health. Having specialized degree and experience in the areas of medical genetics and counselling, Genetic Counsellors not only helps public to understand implication of genetic contributions to disease both medically and physiologically, they are the intermediate link between the care givers and care takers. Providing support and information to individuals, couples and families who have genetic concerns, Genetic Counsellors serves as the resource person in regards to identifying risk, analyze and interpret inherited disease-associated pattern and review options available with such families.

Special Instructions

Please submit medical records or clinic summary notes, and a signed consent form when ordering exome testing. Testing will not be initiated until these documents are received.

How to collect and refer samples for ExomSure | Dx

  • Informed Consent and Documentation

Inform the patient about the test, its benefits and caveats. Get the informed consent and fill Test Requisition Form.

  • Sample collection

Collect whole blood sample in EDTA (purple top) Tube: 5-10 ml for all ages. Please mark the tubes appropriately.

  • Transportation

Refrigerate until time of shipment. Ship sample within 24 hours of collection at room temperature to the Eurofins Clinical Genetics India Pvt. Ltd. address.