NGS​ – Next-generation sequencing

Overview

Reporting & results

Test results are interpreted based on the recommendations and guidelines of the American College of Medical Genetics and Genomics (ACMG) and the European Society of Human Genetics (ESHG) as described below.

Different type of results can be obtained:

• Pathogenic or likely pathogenic variant has been identified
• The identification of a pathogenic or probably pathogenic variant associated with the clinical phenotype under study indicates that the result is compatible with the diagnosis of that disease or clinical condition.
• This scenario will allow to provide genetic counselling or personal guidance regarding possible medical treatments, disease progression, reproductive / prevention strategies and potential implications for other family members.
• No pathogenic or likely pathogenic variant has been identified
• The absence of pathogenic or probably pathogenic variants associated with the clinical phenotype under study indicates that the molecular cause of the disease or condition has not been identified. This result does not confirm nor rule out the clinical indication of the test and does not guarantee that the individual will be healthy or free from other genetic disorders or medical conditions. For this reason, this result does not eliminate the risk for future offspring. A negative result may be explained by several causes, including limited genetic knowledge and limitations associated with the methodology used.
• Inconclusive / Variant of Uncertain Significance (VUS)
• A “variant of uncertain significance” (VUS) is a genetic change whose clinical impact on the patient is not yet known. The presence of a VUS does not clarify whether the patient has an increased risk to develop the genetic disease or if it could be a normal genetic variant. Further analysis may be recommended, including testing both parents as well as other affected and unaffected family members. Sometimes, performing ancillary tests is necessary to prove the phenotype that the individual presents. Detailed medical records or information from other family members may be needed to help clarify the result.
• Result interpretation is based on currently available knowledge in the medical literature, research, and scientific databases. New information that becomes available in the future, may replace or add to the data that Igenomix used to interpret the results. Re-analysis of the results in previously issued reports considering new evidence is not routinely performed but is available upon request. This result does not confirm nor rule out the clinical indication of the test and does not guarantee that the individual will be healthy or free from other genetic disorders or medical conditions. For this reason, the results does not eliminate the risk for future offspring.

Sample Requirements

 For Prenatal Diagnostic:  

• Previous contact with the laboratory is strongly recommended to properly plan the case, prenatal deadlines and anticipate possible issues. 
• Maternal blood sample must be sent with all products of conception, CVS and amnio samples.  
• Other family samples could be requested as positive control samples. 
• Priority will be given to all prenatal samples. 

A thorough labelling of the tube with unique identifying information is required, incorrect labelling can lead to rejection of the sample. The minimum required information to identify and accept a sample is: Patient’s full name, Date of birth, Gender and Medical Record Number.

The ‘informed consent’ and the ‘test requisition from’ must be properly filled-in and signed by the patient and doctor.

Methodology

Limitations

• NGS sequencing is a gene-specific test for the analysis of a small subset of genes.
• NGS sequencing is able to identify mosaic mutations present in as low as 10% of the cells.
• NGS sequencing cannot readily identify partial or whole gene deletions, because they cannot be amplified appropriately.