AION Results

AION results contains the variants automatically identified by AION as the most relevant in the case. To address the diverse needs of clinical diagnostics and research exploration, AION provides two different lists of prioritised variants;

1. AION Smoking Guns -  represent the most stringent list of strong diagnostic candidates, where all available evidence consistently points to their potential as disease-causing candidates for the case. We recommend starting the case analysis from this list. However, the Smoking Guns detection is optimized for specificity, which means that it may not be present in all cases.
   One of the key features driving the Smoking Guns ranking is HPO (Human Phenotype Ontology) similarity. Consequently, if HPOs are not provided, this list is expected to be nearly empty, since the absence of phenotype data limits the ability to prioritize candidates with high confidence.  See more info below.
2. AION Clues - full list of potential candidates with an indication of potential pathogenicity for the case. AION Clues is optimised for sensitivity, and aims to provide potential disease causing candidates even for the hardest of cases. See more info below.
   
   

AION Smoking Guns

AION Smoking Guns is the best place to start analysis. It contains strong diagnostic candidates fulfilling all the below criteria:

1. Molecular evidence supporting that
   1. Variants have molecular characteristics suggesting they are damaging for the gene function.
   2. Variants may be known to be disease-causing, likely pathogenic or pathogenic
   3. The gene affected by the variant is confidently associated with the disease.
2. Phenotypic evidence supporting that the patient phenotype matches the expected phenotypic features of the disease.
3. Segregation and inheritance evidence supports that the genotype in the patient and family members (if available) follow the expected segregation patterns for the related genetic disease.

AION Smoking Guns might not be present for your case. When this happens it means that AION has not identified a very strong and clear disease causing candidate for your case. This might be due to a missing patient phenotype description, and adding that might help.

In all your cases AION will still be providing you with AION Clues, to support you to start your analysis with potential candidates for your case.

AION Clues

AION Clues are the next best place to continue the analysis, if you have already reviewed AION Smoking Guns. It contains potential diagnostic candidates that show evidence of pathogenicity, including the AION Smoking Guns and other candidates that are might be lacking some evidence or the evidence is not strong enough for claiming its position as a AION Smoking Gun. 

Evidence of pathogenicity is evaluated based on molecular, phenotypic, segregation and database evidence in a less stringent way than with AION Smoking Guns.

AION Clues provides a wide range of options ideal for cases where the solution is not as clear and are available also when no patient phenotype is entered.