The analysis performed using Next Generation Sequencing (NGS) is designed to examine the coding regions and splice junctions of the genes included in the test.

The sequencing analysis allows for the detection of single nucleotide variants (SNVs) and large deletions/duplications in the analyzed genes.

The variants are classified according to ACMG/AMP interpretation standards using public databases, including dbSNP-NCBI, ClinVar-NCBI, and gnomAD. Only pathogenic or likely pathogenic variants will be reported.

Benign variants, likely benign variants, and variants of uncertain significance will not be reported, but they may be noted under certain circumstances. The classification of variants is based on the understanding of the genes and variants at the time of analysis; further knowledge acquired in the future may lead to the reclassification of the identified variants.

Although NGS technology and bioinformatics analysis significantly reduce the impact of pseudogene sequences or other highly homologous sequences, these can still occasionally interfere with the technical ability of the analysis to identify pathogenic variants.

Orthogonal methods may be used to confirm variants with low quality scores and to meet coverage standards.

This test will not detect certain types of genomic alterations that can cause diseases, including translocations and inversions, repeat expansions (e.g., trinucleotide or hexanucleotide repeats), alterations in most regulatory regions (e.g., promoter regions), or intronic regions more than 20 bp from an exon.

This test is not designed or validated to detect somatic mosaicism events or somatic mutations.

The carrier test for Fragile X provides information on the carrier status of Fragile X Syndrome, which is caused, in the majority of cases, by expansions in a repeated sequence (CGG)n.

The test is performed using fluorescent PCR amplification of the trinucleotide repeat region located in the 5' UTR of the FMR1 gene.

The method does not allow for the detection of single nucleotide variants (also known as point mutations), gene deletions and/or duplications, or the methylation status of the gene.

The analytical detection rate of Genescreen is high and varies depending on the individual diseases. The residual risk is the probability that the tested patient is a carrier even after testing negative on the screening test.

The residual risk is closely related to the frequency of carriers of the disease and the detection rate of the test for that condition.

The frequency of carriers can vary widely among different populations/ethnic groups. The residual risk provided by Genescreen is calculated using an internal algorithm.