Large CNVs and regions of homozygosity (ROH) can affect multiple genes

The list contains two types of tiles - gene tiles and region tiles

Gene tiles represent genes that intersect the variant borders.

The left side of the tile lists the gene name, transcript, inheritance models associated with the gene, and what areas of the gene were affected by the variant.

On the right side, there are the top conditions that are associated with the gene. Clicking on “See all” will take you to the full list of associated conditions.

Below the condition is the gene’s dosage-sensitivity scores, based on Clingen Dosage Sensitivity Map. Genes with strong evidence for haploinsufficiency (HI) are likely to be sensitive to copy-number reduction, while genes with evidence for triplosensitivity (TS) are likely to be sensitive to copy-number amplification.

Detail explanation about the different values for the dosage-sensitivity score can be found here.

Clicking on the tile itself or the arrow in the right will expand the tile to show a summary about the gene and its role.

The Clingen Dosage Map also lists pathogenic CNV regions. If such regions are encompassed completely within the variant borders, they appear in the Genes and Regions as a region tile (example below):

instead of a gene name and transcript, the region tile has the region cytogenetic location and genomic coordinated on the left side of the tile. Clicking on the tile expands it to show the full region name.

In the case of a large variant that affects many genes and regions, you can filter the list using the filters at the top of the page:

The list can be sorted using the “Sort by” parameters on the top left corner of the page.

Inputting your case phenotype brings up the genes with associated conditions that match your phenotype search. Phenotypes from your list that match the genes will be listed at the bottom of the gene tile, and the strength of the connection between the gene and the phenotypes is indicated by the gauge on the bottom-right corner.