Evidence page

The Evidence page presents the most relevant evidence behind the automatic variant classification suggested by the AI Shortlist. This view can be generated for any other variant after the variant has been manually tagged.

The Evidence page is accessible from:

1. Candidates tab: click on the variant bar

2. Variant page: go to the Evidence section andclick on the See evidence button under the Evidence box.

You can switch between the graph and text view by clicking on the link on top of the page (Show evidence graph or Show evidence as text, respectively). The graph view is helpful for exploring the data, while the text view is relevant for collecting notes.

AI Shortlist collects data from credible studies and public databases in an internal knowledge base that maps complex connections between variants, genes, mechanisms, diseases, and phenotypes.

Concise evidence for the particular variant is highlighted on the Evidence page. This includes:

1) Variant information

The main effect of the variant, its HGVS nomenclature for coding DNA and protein changes, and zygosity, including if the variant is de novo.

2) Gene information

Gene symbol, if the gene is tolerant to variation, and assumed inheritance mode in the case under review. This is suggested based on the observed level of genotype-phenotype co-segregation and inheritance mode of the genetic condition (reported or suspected).

In addition to the conventional inheritance modes (Autosomal Dominant, Autosomal Recessive, Compound Heterozygote Autosomal Recessive, X-Linked Dominant, X-Linked Recessive), the platform also employs Autosomal Dominant Partial Penetrance and Partial Autosomal Recessive designations*.*

Autosomal Dominant Partial Penetrance is used when the gene-associated condition is AD, and the variant is Het in the test subject and at least one of their parents. This suggests that the phenotypes may be due to incomplete penetrance of the genetic condition.

Partial Autosomal Recessive is used when the gene-associated condition is AR and the variant in the test subject is Het. This helps to account for the possibility that another causative variant is undetected - in the same (compound heterozygosity) or another (digenic inheritance) gene.

3) Disease information

Condition name as suggested by OMIM, other disease databases or in the literature.

4) _Patient Phenotypes_

Proband's phenotypes that match phenotypes reported for the suspected disease. Exact, indirect, and matches by ascendance are considered.

5) _Unconfirmed Disease Phenotypes_

Phenotypes reported for the suspected disease but not observed in the proband.

6) _Unmatched Patient Phenotypes_

Phenotypes observed in the proband but not known to be manifested as part of the suspected disease.

Follow the links to the primary sources to explore the evidence further. The links are in the References section (text view) and are accessible by hovering over the arrows (graph view).

The evidence graph can be manually edited to include additional evidence for the case's resolution. To enter the edit mode, click on the pencil icon in the top left corner of the page. In this mode, you can edit, add, and delete text boxes.