InTAD

ClinTAD is a free browser-based tool designed to assist clinicians and geneticists in interpreting copy number variants (CNVs) in the context of topologically associated domains (TADs). This tool is particularly useful when examining CNVs identified by cytogenomic microarray, which can disrupt DNA structural elements such as TADs and exert a pathogenic effect.

Recent primary research has suggested that CNVs can have a more significant impact on human health than previously thought and that their effects can extend beyond the disruption of protein-coding genes within a given region. As such, the development of ClinTAD represents an essential step in integrating these discoveries with current clinical practices, as it allows for the interpretation of CNVs in the context of their broader genomic environment.

To evaluate the effectiveness of ClinTAD, a study was conducted using 209 randomly selected single-nucleotide polymorphism microarray cases with a total of 236 CNVs. The study compared 118 CNVs classified as variants of uncertain clinical significance (VUS) to 118 CNVs classified as benign. The results showed that a higher proportion of VUS had at least two genes in a nearby TAD related to a phenotype seen in the patient based on Human Phenotype Ontology (HPO) annotation.