Disease Association Filters
Last updated
Last updated
This page summarizes filters related to variant – disease and gene – disease associations. Filter availability can vary depending on the selected variant categories. If filters are applied to more than one variant category in the same condition group, only filters relevant for all variant categories are available. For more information, refer to .
In addition to filtering by the gene list, variants can be filtered by genes based on their associations with diseases and phenotypes.
Select the genes filter.
In the displayed dialog box window, select the Include genes from the diseases checkbox.
Start typing a phenotype or disease to display a list of potential matches to add to the list.
Select a checkbox next to Resource to include it in the list.
Select a high, medium, or low confidence score.
Select an overlap distance between 0.00 and 1.00.
The disease and related diseases display in the Related Diseases area with the distance and gene count. Deselect any unnecessary related diseases.
Add any other genes to the gene list.
Add additional genes in the Additional genes area.
Select Apply to save changes to the gene list.
The following tables detail the ontology sources that Connected Insights uses to determine relationships between genes and diseases.
Phenotype to gene search finds similar phenotypes and diseases across various ontology sources, independent of the underlying vocabulary in each source. If an equivalent concept does not exist across the sources, Connected Insights calculates the distance between nodes in the ontological hierarchies and assigns a score from 0 to 1, where:
Values closer to 0 indicate that the concepts are more equivalent. A value of 0 indicates that the concepts are the same.
Values closer to 1 indicate that the concepts are more dissimilar. A value of 1 indicates that the concepts can only be connected at the root node and are therefore excluded from query results.
The determination of distance accounts for the fact that sibling concepts on leaf nodes (eg, hypertrophic cardiomyopathy, and dilated cardiomyopathy) are more closely related to each other than siblings close to the root (eg, abnormal vascular morphology, and abnormal heart morphology).
Confidence scores for gene - disease associations are calculated using the following rules:
Expert-curated data from OMIM, HPO, Phenopedia, and ClinVar are assigned a high confidence score.
High, moderate, or low confidence scores are converted from GeL PanelApp strong, medium, and low scores, respectively.
GTR confidence scores are based on information content metrics, which measure the specificity of a genetic test for a particular phenotype and a gene.
GeneRIF associations, which are derived using data mining, and assigned medium confidence.
Filters variants based on gene role in cancer annotated by COSMIC Cancer Gene Census (CGC).
Filters variants based on genes with known gene-disease associations in the OMIM database.
Present in OMIM — An OMIM entry exists for the gene.
Has associated OMIM phenotypes (including ?) — A relationship exists between the phenotype and a matching gene at the transcript level. Provisional relationships, indicated by "?" in OMIM, are included.
Has associated OMIM phenotypes (excluding ?) — A relationship exists between the phenotype and a matching gene at the transcript level. Provisional relationships, indicated by "?" in OMIM, are excluded.
Selecting associated phenotypes enables options to refine the filter by mode of inheritance.
❕ The COSMIC filter is only selectable for small variants.
Filters by number of samples in cancer hotspots.
Filters on interpretation categories and the review status provided in the ClinVar database.
To filter by ClinVar review status, use the definitions provided from the ClinVar status review guidelines on the National Center for Biotechnology Information website.
Filters by presence in the COSMIC database. For more information, refer to .
Resource | Description |
OMIM | Online Mendelian Inheritance in Man |
HPO | Human Phenotype Ontology |
Phenopedia | Human Genome Epidemiology (HuGE) |
GEL PanelApp | Genomics England PanelApp |
ILMN | • Clinvar – NCBI ClinVar •MedGen – NCBI portal to information about conditions and phenotypes related to Medical Genetics. •GTR – NCBI Genetic Testing Registry •GeneRIF – NCBI Gene Reference into Function |
Resource | Description |
ICD-9 | International Classification of Diseases, Ninth Revision |
ICD-10 | International Classification of Diseases, Tenth Revision |
MeSH | Medical Subject Headings |
UML | Unified Medical Language system. A repository of ontology resources. |
SNOMEDCT | Systematized Nomenclature of Medicine Clinical Terms |
Role in Cancer | Description |
TSG | Known tumor suppressor gene (TSG). |
Oncogene | Known oncogene. |
Fusion | Known fusion gene. |
Mode of Inheritance | Description |
AD | Autosomal Dominant |
AR | Autosomal Recessive |
XL | (X-linked) |
XLD | (X-linked Dominant) |
XLR | (X-linked Recessive) |
YL | (Y-linked) |
MI | Mitochondrial |
Mu | Multifactorial |
DD | Digenic Dominant |
DR | Digenic Recessive |
SMu | Somatic Mutation |
SMo | Somatic Mosaicism |
IC | Isolated Cases |
Interpretation Category | Definition in Connected Insights |
Pathogenic | The variant has at least one aggregate variant record (VCV entry) or aggregate variant –disease record (RCV) with classification category Pathogenic in the ClinVar database. |
Likely Pathogenic, UncertainSignificance, Likely Benign, Benign | The variant has at least one aggregate variant record (VCV entry) or aggregate variant –disease record (RCV) with classification category Pathogenic in the ClinVar database. |
None | The variant has no records in ClinVar or has at least one aggregate variant record (VCV entry)or aggregate variant – disease record (RCV) with interpretation categories Drug Response,Protective, and others (any other categories excluding Pathogenic, Likely Pathogenic,Uncertain Significance, Likely Benign, and Benign). |
Number of Stars | Definition in Connected Insights | Review Status Descriptions |
Four | The highest review status across all VCV and RCV records for the variant is four stars. | Practice guideline. For more information,refer to the ClinVar status review guidelines on the National Center for Biotechnology Information website. |
Three | The highest review status across all VCVand RCV records for the variant is three stars. | Reviewed by export panel. For more information, refer to the ClinVar status review guidelines on the National Center for Biotechnology Information website. |
Two | The highest review status across all VCVand RCV records for the variant is two stars. | Criteria provided, multiple submitters, no conflicts. Two or more submitters with assertion criteria and evidence (or a public contact) provided the same interpretation. |
One | The highest review status across all VCV and RCV records for the variant is one star. | Criteria provided, conflicting interpretations. Multiple submitters provided assertion criteria and evidence(or a public contact) but there are conflicting interpretations. The independent values are enumerated for clinical significance. |
None | The highest review status across all VCV and RCV records for the variant is no stars. | No assertion criteria provided. For more information, refer to the ClinVar status review guidelines on the National Center for Biotechnology Information website. |