Table 2 Key features of CardioClassifier
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 parameterized 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 | ✓ | — | ✓ | ✓ |
Evidence used to generate classification displayed | The thresholds and data used in CardioClassifier is transparent and printed on the report | ✓ | — | — | — |
Knowledge base of case-level annotations | We have created a “knowledge base” whereby manually curated case-level evidence is stored and used to populate variant reports | ✓ | — | — | — |
