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Glossary

Definitions of the clinical and technical terms used throughout this documentation. Hover over any abbreviation in the docs (for example ACMG, VAF, NCCN) for a short tooltip; this page has the longer definitions.

Classification and evidence

ACMG

American College of Medical Genetics and Genomics. Author of the widely used standards and guidelines for the classification of sequence variants in germline testing, defining criteria (PVS1, PS1–PS4, PM1–PM6, PP1–PP5, BS1–BS4, BP1–BP7) that combine to produce one of five classifications: Pathogenic, Likely Pathogenic, Uncertain Significance, Likely Benign, or Benign.

AMP / ASCO / CAP

Joint guidelines from the Association for Molecular Pathology, the American Society of Clinical Oncology, and the College of American Pathologists for the interpretation and reporting of sequence variants in cancer. Defines a four-tier system (Tier I–IV) based on clinical evidence level. See Tier definitions below.

NCCN

National Comprehensive Cancer Network. Publishes practice guidelines widely used in oncology for treatment selection, screening, and surveillance. Referenced in somatic variant reports as evidence for actionability.

ELN

European LeukemiaNet. Publishes diagnostic and therapeutic recommendations for haematologic malignancies. Referenced in relevant report templates.

ICC

International Consensus Classification. Classification system for myeloid neoplasms and acute leukaemias.

WHO

World Health Organization. Maintains classification systems for haematologic and lymphoid neoplasms used alongside ICC.

CKB

Clinical Knowledge Base (Genomenon). External evidence database surfaced in the variant browser for somatic cases.

CIViC

Clinical Interpretation of Variants in Cancer. Community-curated evidence database surfaced alongside CKB entries.

FDA

United States Food and Drug Administration. Its approval status for a drug is used as an evidence level indicator in somatic variant tiering.

Tier classifications

Tier IA

AMP / ASCO / CAP Tier I Level A — variant with strong clinical evidence; FDA- approved therapies or included in professional guidelines (for example NCCN for the patient's tumour type).

Tier IB

Tier I Level B — strong clinical evidence from well-powered studies with consensus from experts.

Tier II

Potential clinical significance — evidence based on smaller studies or on clinical trials, and may include drugs used off-label or in other tumour types.

Tier III

Variants of unknown clinical significance. Present in the sample but not yet associated with actionable evidence.

Tier IV

Benign or likely benign variants. By default these are not auto-populated into reports; curators may add them manually where relevant.

Regulatory

CLIA

Clinical Laboratory Improvement Amendments. US federal regulatory standards for clinical laboratory testing performed on humans. iFlow's sign-off workflow and audit trail are designed to support CLIA documentation requirements but does not itself grant CLIA compliance.

CE-IVD

Conformité Européenne marked for In Vitro Diagnostic use. An older directive now largely superseded by IVDR.

IVDR

In Vitro Diagnostic Regulation (EU 2017/746). The current European regulatory framework for in vitro diagnostic devices.

LDT

Laboratory-Developed Test. A test designed, manufactured, and used within a single laboratory.

RUO

Research Use Only. A label indicating that a product is not intended for diagnostic use.

Biology and file formats

VAF

Variant Allele Frequency. The fraction of sequencing reads at a position that support the variant allele; used in somatic cases to distinguish tumour subclones from germline variants.

VCF

Variant Call Format. Text-based tabular format for storing called variants; typically bgzipped and tabix-indexed for random access.

BAM

Binary Alignment Map. Compressed binary format for aligned sequencing reads.

FASTQ

Sequencing read format that stores the base calls and per-base quality scores produced by a sequencer.

HGVS

Human Genome Variation Society nomenclature — the standard way to name variants at the DNA, RNA, and protein level (for example NM_007294.4:c.5266dupC or p.Gln1756ProfsTer74).

GRCh38

Genome Reference Consortium Human build 38, published in 2013. iFlow pipelines and reporting target GRCh38.

GRCh37

The prior reference build (also known as hg19). Not supported by current iFlow pipelines.

SNV

Single Nucleotide Variant — a one-base substitution.

CNV

Copy Number Variant — a gain or loss of a genomic segment.

InDel

Insertion or deletion variant, typically smaller than 50 bases.

Clinical workflow

Order

The case-level record. An order groups one or more samples, selects a test mode (hereditary or somatic), runs through a labflow, and ends with a signed report. See Orders.

Subject

The individual whose material is being tested. A subject can be associated with one or more samples. See Subjects.

Sample

A physical specimen from a subject. Samples carry sequencing files (VCF, BAM, FASTQ) and their metadata. See Samples.

Analysis

A run of a pipeline against a sample's inputs. Produces VCFs and auxiliary outputs. See Analyses.

Labflow

The configurable state machine that an order follows. Defines stages, allowable transitions, and the roles that may act on each stage. See Labflows.

Proband

In a family-based hereditary test, the index individual through which the family is ascertained.

Sign-off

The act of approving a report and generating its immutable signed PDF. The order advances to completed once sign-off succeeds.

Amendment

A new signed report that supersedes an earlier one, created when post-sign-off changes are required. The original signed PDF is preserved.

Platform

iFlow

Intelliseq Flow. The product this documentation describes.

LIS

Laboratory Information System. The system of record used by the laboratory to track specimens and test orders.

LIMS

Laboratory Information Management System. Often used interchangeably with LIS.

IGV

Integrative Genomics Viewer. Used alongside iFlow for interactive inspection of aligned reads.