MediExome Solo

Exome sequencing and targeted bioinformatic analysis in the patient

Test description

MediExome Solo relies on the sequencing the patient’s exome. During exome sequencing, all coding regions and splice sites of the 20’000 protein coding genes are sequenced simultaneously. The produced data is analyzed in order to identify the individual variations of the patient. This rigourous analysis is performed with the help of a suite of bioinformatics programs by our experts; it is applied only on the genes relevant to the patient’s clinical pictures (variable gene panel according to the pathology). A reanalysis of the data taking into account recent progress in scientific knowledge or new phenotypic elements is possible at any time.

The variants retained are interpreted by our team of Genetics experts, which includes clinical geneticists, molecular biologists and bioinformaticians. The clinical information provided by the physician is of the utmost importance to interpret the variants. The variants interpreted as pathogenic or likely pathogenic, i.e. considered responsible of the phenotype, are reported.

 

Indications

  • Suspicion of monogenic disease, particularly in case of known genetic heterogeneity, i.e. several genes involved in the same clinical picture
  • Complex medical condition, without an established etiologic diagnostic

This technology is applicable to all medical specialties. The diagnostic yield, .i.e. the probability of identifying a molecular cause, is in average 25-30%; it varies according to the type of disease.

Technical specifications

MediExome Solo allows the detection of punctual variants (Single Nucleotide Variants, or SNVs), small insertions or deletions of less than 30 bp (indels) and somatic variants with a mosaicism of more than 20%. The Copy Number Variants (CNVs) can possibly be visualized if they relate to more than 3 consecutive exons. The percentage of nucleotides covered at least at 20x on the exons and splice sites of the genes of interest is in average about 99%; it varies according to the gene panel. Any variant reported is confirmed by either Sanger sequencing or another method (MLPA, array-CGH).

Sample

4-6 ml of EDTA blood, not centrifuged.

Turnaround time

8-10 weeks after reception of the sample, the request form, the signed consent and, depending on the situation, a document issued by the insurance confirming the reimbursement.

Familial segregation analysis

The candidate variants are confirmed in a targeted fashion in the index case. If available, the samples of the parents and/or other family members allow to perform a familial segregation analysis in order to facilitate or strenghten the variant interpretation.

Reimbursement

This analysis is included in the OPAS List of Analysis and the reibursement is done through the patient’s insurance.

Limitations

This analysis does not detect any expansion of repeated regions (including trinucleotides), any variant in regions with insufficient coverage, any variant in non-analyzed regions (regulatory elements, introns),  any variant in genes not included in the tested gene panel or any variant present in low mosaicism. Furthermore, exome sequencing is not reliable to detect translocations, insertions, deletions and duplications of more than 15 bp, Copy Number Variants (CNVs) of whole exons, variants in genes with very homologous pseudogenes and variants in the mitochondrial genome.

Performance statistics

Sensitivity (TP/(TP+FN)) Specificity (TN/(TN+FP))
SNV 99.94% >99.99%
Indel 96.99% >99.99%

 

% coverage at 20x % coverage at 30x Average coverage
All genes associated to a phenotype (CGD) 99.10% 98.88% 137.85