Update of the Diagnostic Panel for Liver Diseases

The Diagnostic Panel for Liver Diseases has been extensively revised and expanded to include a higher-level gene set for cholestasis (LIV-10).

The exact pathomechanism of liver disease is often difficult to determine. Therefore, a new overarching gene set has been created to increase the diagnostic panel’s clinical usability. The new gene set for cholestasis (LIV-10) includes 42 genes and facilitates clarification of the genetic cause of liver disease. The gene sets for the diagnosis of progressive familial intrahepatic cholestasis (LIV-01) and for the clarification of lysosomal storage diseases with liver involvement (LIV-06) can still be requested separately.

The diagnostic panel for liver diseases includes the following gene sets:

  • Progressive familial intrahepatic cholestasis (10 genes, LIV-01).
  • Lysosomal storage diseases with liver involvement (5 genes, LIV-06)
  • Cholestasis (42 genes, LIV-10)

Additional gene sets clinically associated with liver involvement can be requested through the Diagnostic Panel for Metabolic Diseases, incl. Mitochondriopathies.

Analysis based on in-house exome enrichment

For all diagnostic panels, we sequence the whole exome. Exome sequencing is based on CeGaT ExomeXtra®, which we developed to generate the best sequencing data for genetic diagnostics. Since CeGaT ExomeXtra® covers all known pathogenic intronic and intergenic variants in addition to all protein-coding regions, it provides an excellent basis for genetic diagnostics.

Further information on our Diagnostic Panel for Liver Diseases can be found here.

We will be happy to assist you in selecting the most appropriate diagnostic strategy for your patients. Call us at +49 (0) 7071 565 44 55 or send us an e-mail at diagnostic-support@cegat.com.

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Closing of the Corona Testing Site at the Fairground

After almost three years of the Corona pandemic, most of the legal protective measures are no longer in place due to the population’s low case numbers and high immunity. Experts speak of the transition to the endemic phase. We have also observed for months that only a few people are still getting tested at our testing site at the fairground.

 Against the background of these encouraging developments, we are discontinuing the operation of our testing site as of February 28th. Thanks to our reliable corona diagnostics, we contributed to the containment of the pandemic with one of the first testing sites in Tübingen – until the infection subsided.

We continue to offer on-site testing services for companies.

Review of almost three years of Corona diagnostics

CeGaT has supported the Corona regulations from the beginning with various test concepts. As the first provider in Germany, we performed Corona antibody tests and continuously expanded our portfolio – from genome sequencing to pool or express PCR tests. With up to seven test stations, we helped the Tübingen city council to implement the “Open with Safety” model project. For various companies, such as Daimler AG or Stuttgart Airport, we were the contact for the planning and implementing of hygiene concepts. In total, we performed 437,369 PCR tests and 67,112 antibody tests by the end of February.

If you have any questions, please do not hesitate to contact us at diagnostic-support@cegat.com.

New Service: Family Planning Panel

With the Family Planning Panel, you can determine your childs’ risk for possible hereditary diseases even before pregnancy. For this purpose, 1,943 genes that can lead to early severe childhood diseases are examined.

Many people carry disease-causing variants in their genetic material without knowing it and without becoming ill themselves. For example, if both parents are carriers of a disease-causing gene variant, there is a 25 percent risk of having a child with this hereditary disease. With the Family Planning Panel, both common genetic disorders, such as cystic fibrosis or spinal muscular atrophy (SMA), as well as very rare syndromes, are specifically investigated. For the evaluation, we combine the genetic data of both parents and determine the risk for your child.

The Family Planning Panel at a glance:

  • The panel includes 1,943 genes that cause severe disease in early childhood.
  • Targeted analyses for fragile X syndrome (FMR1 repeat) and spinal muscular atrophy (SMN1-MLPA) are also performed.
  • Data from both parents are analyzed together and summarized in an easy-to-read report.

The result of the genetic testing, in combination with human genetic counseling, allows you to make an informed decision. In this way, you can inform yourself at an early stage about the various options, such as prenatal diagnostics or early, targeted treatment of the newborn.

The new panel can be requested here.

For more information, please get in touch with us at diagnostic-support@cegat.com for advice.

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Expansion of the Diagnostic Panel for Fertility

The Diagnostic Panel for Fertility has been expanded by 68 genes and now includes 203 genes associated with a genetic fertility disorder. Three gene sets have been newly integrated. Thus, the panel can also diagnose hereditary asthenozoospermia or clarify unintended childlessness without a clear indication. In addition, the existing gene sets were extensively reorganized in terms of content, and the composition was revised based on the current data situation.

We have developed a new gene set for the diagnosis of hereditary asthenozoospermia. This gene set (FER14) contains 31 genes in which alterations are causative for impaired sperm motility.

To facilitate the clinical usability of the Diagnostic Panel for couples with an unfulfilled desire to have children, two additional overlapping gene sets are now available to clarify infertility without indicative preliminary findings.

The gene sets for Primary Ovarian Insufficiency|POI (FER01) and Premature Ovarian Insufficiency|POF (FER02) have been merged and are now requestable as Ovarian Insufficiency (FER02), as a clear delineation is often difficult in clinical practice.

Analysis based on in-house exome enrichment

The Diagnostic Panel for Fertility is based on exome sequencing with CeGaT ExomeXtra®. CeGaT ExomeXtra® covers all protein-coding regions as well as all known pathogenic intronic and intergenic variants. It thus provides the best basis for genetic diagnostics.

Further information on our Fertility Diagnostic Panel can be found here.

We would be happy to support you in selecting the most targeted diagnostic strategy for your patients. Call us at +49 (0) 7071 565 44 55 or send us an e-mail at diagnostic-support@cegat.com.

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Studies confirm: Examination of tumor tissue only without comparing it to normal tissue can lead to misdiagnosis and incorrect treatment decisions

International experts agree: tumor tissue and normal tissue must be examined and compared for tumor diagnostics. The examination of tumor tissue alone leads to misdiagnoses.

CeGaT has been following this approach for 10 years. Tumor and normal tissue are always examined and compared. This is the only way to reliably distinguish somatic (tumor-specific) from germline variants (inherited variants). A medical report is then drawn up on this basis. The CeGaT report not only shows the tumor-specific variants and relevant germline alterations; it also always gives specific scores for TMB, MSI, and HRD. Of course, tumor-specific therapy recommendations are included as well as information on the drugs and a representation of the affected pathways.

Knowledge of tumor-specific variants is essential for a therapy recommendation. If these are not correctly determined because only tumor tissue was examined, therapies may be proposed that also attack healthy cells. In addition, the total number of changes in the tumor (TMB) cannot be correctly determined, which complicates the indication for immunotherapies.

The following recent studies confirm our approach:

TMB (Tumor Mutational Burden) – Overestimation due to lack of comparison with normal tissue.

Nassar et al. 20221 have shown that tumor tissue sequencing alone can lead to overestimated TMB values. This applies in particular, but not exclusively, to non-European patients. The reason for this TMB overestimation is the missing comparison of the sequencing data of the tumor with the data of the patient’s normal tissue. In tumor-only panels, the germline variants are identified by bioinformatic comparison with reference data (e.g., GnomAD), which are predominantly based on data from patients of European descent. Asian or African decendant patient data is underrepresented in the database, so germline variants are incorrectly assigned to somatic and thus tumor-specific variants. In addition, the heritability of a tumor disease is often overlooked.

Consequently, human genetic counseling of patients, and in some cases family members, about the existing familial predisposition is impossible. In addition, necessary screening examinations cannot be offered, which may lead to avoidable late detection of cancer in family members.
Furthermore, Nasser et al. demonstrated that ancestry bias in TMB classification is directly reflected in treatment outcomes. Patients with non-small cell lung cancer and overestimated TMB levels did not show improved survival after immune checkpoint treatment (ICI) compared to patients whose TMB levels were correctly estimated thanks to paired tumor-normal comparison. Tumor-normal matching might avoid ineffective ICI therapies with side effects, and appropriate treatments could be applied directly without losing time.

To avoid TMB misestimation, the authors call for sequencing of tumor and normal tissue.

Tumor-to-normal tissue comparison helps interpret pathogenic germline mutations.

In a study with more than 17,000 patients, Srinivasan et al. 20212 investigated the extent to which cancers that occur in patients with inherited pathogenic and hence, potentially disease-causing variants, are caused by a germline defect. Their comprehensive analyses of tumor and normal tissues indicate that the mere presence of a germline mutation, even in a canonical/common cancer, does not mean that the tumor is caused or primarily driven by the altered germline allele. Instead, the penetrance of a germline alteration in a particular gene, the zygosity of alterations, and the presence of a somatic “second hit” are essential determinants, among others. This misinterpretation can lead to completely inefficient therapeutic proposals. An example would be a BRCA2 mutation that did not cause the tumor development but is present by chance. A tumor-to-normal tissue comparison clearly shows this by the absence of HRD (homologous recombination deficiency). PARP inhibition would not be effective here.

Therefore, to obtain a complete picture of a tumor and to be able to determine the role of germline variants in disease pathogenesis, as well as to identify somatic alterations as drivers in a given tumor, it is necessary to identify the somatic alterations by comparing tumor and normal tissue, and to include them in the interpretation of the germline variants. Only the complete picture makes it possible to say with certainty what really is driving a tumor and, thus, what is a promising therapeutic molecular target.


Both studies underline the necessity for comparing tumor and matched normal tissue to develop promising therapy recommendations for the patient.

Furthermore, it is ensured that family-relevant germline variants are not overlooked and can thus be considered in patient care or genetic counseling. This is the only way to address possible consequences for the affected person and other family members if a hereditary variant is detected.

1Nassar et al. (2022). Cancer Cell 40, 1161–1172.
2Srinivasan, P., Bandlamudi, C., Jonsson, P. et al. (2021). The context-specific role of germline pathogenicity in tumorigenesis. Nat Genet 53, 1577–1585.

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