Glossary

Estimated time: 5 minutes

These definitions reflect how each term is used in the module.

A to F

ACMG/AMP classification: A framework that classifies sequence variants as pathogenic, likely pathogenic, uncertain significance, likely benign, or benign. This module begins with variants that have already been evaluated and records their clinical classifications. Learn more about the ACMG/AMP standards.
AlphaMissense: A protein variant-effect prediction model that assigns a pathogenicity score to possible human missense variants using evolutionary and protein-structure information. ProtVar reports the score and its prediction category. Learn more about AlphaMissense.
Application programming interface (API): A standard way for software to request data or services from another system. In this module, APIs keep the source, identifiers, and retrieval steps clear and reproducible. Learn more about APIs.
Bulk tissue: A tissue sample measured as a mixture of its component cell types. GTEx provides bulk-tissue expression, while cell-type resources identify the cellular source of a transcript signal. Learn more about the GTEx project.
Cell type: A group of cells that share biological characteristics. Cell-type-resolved expression can help identify a relevant cell type for follow-up experiments or disease modeling. Explore terms in the Cell Ontology.
Endpoint: A specific API address that accepts a defined request and returns a defined type of data. Learn more about API paths and endpoints.
EVE: Evolutionary model of Variant Effect. EVE uses patterns in protein sequence evolution to predict the effect of an amino acid substitution. ProtVar reports an EVE score and prediction category when they are available. Learn more about EVE.
FoldX: Software that uses an empirical energy function to estimate how a sequence change may affect protein stability or interactions. ProtVar reports a FoldX stability change for the selected TNNT2 missense variant. Learn more about FoldX.

G to M

Gene symbol: A standardized short name for a gene, such as TTN. Gene symbols make it possible to join resources. Checking aliases and identifier changes supports accurate matches. Learn more about human gene-naming guidelines.
GraphQL: An API query language in which a request specifies the fields that should be returned. The Pharos activities use GraphQL to retrieve selected target information. Learn more about GraphQL.
GTEx: The Genotype-Tissue Expression project. This module uses GTEx data to compare candidate-gene expression in selected bulk heart tissues. Learn more about GTEx.
HGVS: Human Genome Variation Society sequence-variant nomenclature. HGVS expressions describe a variant relative to a named reference sequence and should be interpreted together with that sequence accession and version. Learn more about HGVS nomenclature.
HGVSc (hgvs_c): An HGVS description at the coding-DNA level. It usually reports the position and nucleotide change relative to a specific transcript, so the transcript accession is essential for interpreting the value. Review HGVS syntax and examples.
HGVSp (hgvs_p): An HGVS description of an observed or predicted protein-level consequence. Parentheses commonly mark a predicted protein consequence. Experimental evidence can then test that consequence. Review HGVS syntax and examples.
HuBMAP: The Human BioMolecular Atlas Program. This module uses HuBMAP cell data to assess ventricular cardiac myocytes as a possible experimental model. Learn more about HuBMAP.
IDG: Illuminating the Druggable Genome, a program that develops and organizes knowledge about human proteins, with an emphasis on understudied proteins. Learn more about IDG.
JSON: A structured text format commonly returned by APIs. JSON stores information as objects and arrays that analysis code can convert into tables. Learn more about JSON.
Many-to-one join: A table operation in which several variant rows can match one gene row. Used correctly, the result includes every original variant and adds shared gene-level data where appropriate. Learn more about validating joins in pandas.
Median TPM: The median transcripts-per-million expression value across samples in a group. It summarizes relative transcript abundance within a tissue. Protein abundance requires a protein-level measurement. Learn more in the GTEx Portal documentation.
Missense variant: A sequence variant that changes a codon so that one amino acid is replaced by another in the resulting protein. Learn more about missense variants from NHGRI.

N to Z

Normalized expression: An expression value adjusted to make measurements more comparable within a particular dataset. Each resource defines its own scale and normalization method. Learn more in the GTEx Portal documentation.
Pathogenic or likely pathogenic (P/LP): Clinical classification categories indicating different strengths of evidence that a variant contributes to disease. This module records the labels from the prior evaluation throughout the analysis. Learn more about the ACMG/AMP standards.
Percent detected: In this module, the percentage of retrieved HuBMAP records with a value above zero. It provides a different view from average expression and depends on the records, assay, and processing choices represented in the Cells API index. Learn more about HuBMAP APIs.
Pharos: A knowledge portal and API for exploring protein targets, diseases, ligands, and Target Development Levels. This module uses Pharos to review what kinds of follow-up tools or knowledge may already exist for a gene product. Explore Pharos.
pLDDT: Predicted local distance difference test. AlphaFold assigns this confidence score from 0 to 100 to each residue in a predicted protein structure. It describes confidence in the local structural model, while variant-effect predictions address the amino acid substitution. Learn more about pLDDT in the AlphaFold documentation.
ProtVar: An EMBL-EBI resource that maps human missense variants between genomic, coding-DNA, and protein coordinates. It brings together functional, population, structural, and variant-effect information for the mapped protein position. Learn more about ProtVar.
Reference sequence: The accessioned DNA, RNA, or protein sequence against which a variant is described. An HGVS expression can change when a different transcript or sequence version is selected. Learn more about NCBI RefSeq.
REST API: An API style that usually represents data as web resources addressed by URLs and standard HTTP methods. The GTEx, HuBMAP, and ProtVar activities use REST requests. Learn more about REST.
Target Development Level (TDL): An IDG classification describing how well a protein target has been studied and which types of knowledge or tools are available. TDL can help identify an appropriate research next step. Disease evidence addresses disease relevance. Learn more about TDLs in Pharos.
Tbio: A TDL for targets with experimental Gene Ontology annotations or a qualifying combination of publication, GeneRIF, and antibody records. These targets are candidates for focused mechanistic or functional follow-up. Learn more about TDLs in Pharos.
Tchem: A TDL for targets outside Tclin that have sufficiently potent small-molecule binding data. These targets may have chemical tools suitable for experimental investigation. Learn more about TDLs in Pharos.
Tclin: A TDL for targets associated with an approved drug and a known mechanism of action. This can identify established pharmacological mechanisms to examine. Variant and patient evidence determine relevance to a specific case. Learn more about TDLs in Pharos.
Tdark: A TDL for understudied targets that meet IDG inclusion criteria and have limited characterized biology or chemical tools. These targets may require basic protein characterization before targeted experiments are possible. Learn more about TDLs in Pharos.
Transcript accession: A stable identifier for a particular transcript sequence. Transcript choice affects coding positions and protein consequences, so it must accompany an HGVSc or HGVSp value. Learn more about NCBI RefSeq.
UniProt accession: A stable alphanumeric identifier assigned to a protein entry in UniProtKB. For example, P45379 identifies human cardiac troponin T. Pharos and ProtVar use UniProt accessions to refer to protein records. Learn more about UniProt accession numbers.
Variant of uncertain significance (VUS): A variant for which the available evidence supports an uncertain classification. Biological evidence can guide research priorities, and clinical classification requires the complete body of evidence. Learn more about the ACMG/AMP standards.