Table 2. Key features of CardioClassifier.
Included are details of each key feature and which of three currently available tools (Alamut, InterVar and the ClinGen pathogenicity calculator) also includes each feature.
| Feature | Description | CardioClassifier | Alamut | InterVar | ClinGen Pathogenicity Calculator |
|---|---|---|---|---|---|
| Collates data from multiple sources | CardioClassifier retrieves data from multiple databases/resources including ExAC, ClinVar, ACGV and dbNSFP as well as internally derived data | ✓ | ✓ | ✓ | - |
| Takes a standard VCF or variant details as input and annotates with effect on sequence and protein | The Ensembl Variant Effect Predictor is used to annotate all variants according to protein consequence | ✓ | ✓ | ✓ | - |
| ACMG/AMP rules parameterised through expert curation according to specific gene and disease | We have developed expertly-curated gene and disease specific thresholds for 14 computational ACMG/AMP criteria in addition to 3 specifically created ICC specific rules. | ✓ | - | - | - |
| Computational data used to activate ACMG/AMP rules | Each variant is automatically assessed against 17 computational criteria | ✓ | - | ✓ | - |
| Interactive refinement of rules and addition of case-level data | Users can interactively add or remove evidence pertaining to any of the ACMG/AMP rules | ✓ | - | ✓ | ✓ |
| Integration of automated annotations and case-level interactive additions to calculate a classification according to the ACMG logic | The logic from the ACMG/AMP guidelines is used to provide a final classification | ✓ | - | ✓ | ✓ |