Cascade Protocol Genomics Ontology
Layer 2 vocabulary for sequence variants, variant interpretations, haplotypes/diplotypes, copy number variants, sequencing-run metadata, raw-file pointers, pedigrees, and genetic test reports/orders. Bridges Layer 1 standards (HGVS, ClinVar, VRS, HGNC, Sequence Ontology, HPO, MONDO/OMIM/ORDO, ACMG/AMP via LOINC answer codes, ClinGen review-status taxonomy) to Layer 3 patient-facing genetic counseling summaries in checkup:.
DRAFT — pre-stable v1 ontology. Property names, ranges, and structure may change before v1.0 stable release. Three-layer ontology for genomics: Layer 1 (Established): HGVS nomenclature, VRS, ClinVar, HGNC, Sequence Ontology, HPO, MONDO/OMIM/ORDO, ACMG/AMP (encoded via LOINC), ClinGen review-status taxonomy, GA4GH htsget streaming. Layer 2 (genomics:): Variant, VariantInterpretation, SubmitterAssertion, Haplotype, Diplotype, CopyNumberVariant, SequencingRun, RawFile, GeneticTest, GeneticTestOrder, Pedigree, PedigreeMember — RDF resources binding Layer 1 codes to a patient and family with provenance and quality tier. Layer 3 (checkup:): GeneticCounselingSummary, VariantNarrative — patient-facing aggregations and regeneratable narrative (authored separately in the checkup vocabulary).
Sequence Variant
A specific sequence variant observed in a patient sample. Carries the four parallel descriptions of variant identity (HGVS for human readability, ClinVar/VRS for stable computable identity, Sequence Ontology for consequence type, gene for biological context). Distinct from VariantInterpretation, which assigns clinical significance.
Variant Interpretation
A clinical-significance assertion linking a Variant to a single condition (per D-Q5 — multi-condition cases produce multiple Interpretation instances), with ACMG/AMP classification, supporting criteria, and an interpreting laboratory or expert panel. Reclassifications produce new Interpretation instances linked to the prior via prov:wasRevisionOf — interpretations are versioned, not edited. SHACL enforces genomics:condition and genomics:variantInterpreted both at cardinality 1..1 (see genomics.shapes.ttl, TASK-0.2).
Genetic Test Report
Result envelope from a clinical genetic test (panel, exome, single-gene). Aggregates Variant observations, gene panel scope, methodology, and ordering provider. Maps to FHIR DiagnosticReport. For test orders that have not yet resulted, see genomics:GeneticTestOrder.
Genetic Test Order
An order/request for a genetic test, distinct from the resulting GeneticTest. Maps to FHIR ServiceRequest. Counseling workflows track 'ordered but not yet resulted' state via this class. Once the order is fulfilled, link the resulting GeneticTest via genomics:resultedIn.
Gene
A gene reference, identified by HGNC approved symbol and ID. Used as the target of variant observations and gene-disease associations.
Haplotype
A multi-variant unit travelling together on one chromosome — the unit of clinical interpretation in pharmacogenomics (PharmVar star alleles like CYP2C19*2, CYP2D6*4) and HLA typing (HLA-DQB1*02:01). Cannot be expressed as a single Variant. Anchored on fhir:Observation per FHIR Genomics IG haplotype profile.
Diplotype
A pair of haplotypes (e.g., '*1/*2'), required for any pharmacogenomics or HLA typing use case. Anchored on fhir:Observation per FHIR Genomics IG genotype profile.
Copy Number Variant
A structural variant defined by deletion or duplication of a genomic interval, expressed as integer copy number plus interval coordinates rather than HGVS. Required for structural-variant cases (e.g., 13q14 deletion in retinoblastoma). subClassOf genomics:Variant — inherits stable-ID and zygosity properties where applicable.
Sequencing Run
Metadata for a single sequencing run that produced one or more variants. Captures coverage depth, technology, variant-caller version, laboratory certification, and key dates (sample collection, sequencing, file generation). Used to populate the data-quality tier on derived Variants and to trace provenance back to lab process.
Raw Genomic File
Pointer-and-hash record for a raw genomic file (BAM, CRAM, FASTQ, gVCF, VCF, BCF). Cascade does NOT ingest the bytes — only the manifest. The bytes live wherever the user keeps them (lab cloud, local disk, NAS, htsget-served). genomics:fileLocation may be opaque (s3://, https://, file://, or a vendor-specific URI) and is not validated by Cascade.
HGVS Coding-DNA Description
Variant described against a coding-sequence (transcript) reference, e.g. 'NM_000059.4:c.5946delT'. Includes transcript accession with version. This is the form most often cited in clinical reports.
HGVS Protein Description
Variant described at the protein level, e.g. 'NP_000050.3:p.Ser1982Argfs*22'. Use parentheses (p.(Ser1982Argfs*22)) when the protein consequence is predicted from the DNA change rather than directly observed.
HGVS Genomic Description
Variant described against a genomic reference, e.g. 'NC_000013.11:g.32340301del'. Required for cross-transcript joins and for variants outside coding regions.
Reference Allele
The reference base sequence at the variant position, as defined by the reference genome assembly. ATCG[N], typically 1–N bases. Per VCF REF / FHIR Genomics IG LOINC 69547-8.
Alternate Allele
The variant allele sequence at the variant position. ATCG[N] for substitutions/insertions; '-' or empty for deletions; structured forms like ' '/'<DUP>' for symbolic alleles. Per VCF ALT / FHIR Genomics IG LOINC 69551-0.
Genomic Start-End Coordinates
The 1-based inclusive start-end coordinates of the variant on the reference assembly, formatted as 'chrN:start-end' (e.g., 'chr17:43124027-43124028'). Pair with genomics:referenceGenome for full anchoring. Per FHIR Genomics IG LOINC 81254-5.
Protein Consequence Directly Observed
True when the p.HGVS description was directly observed at the protein level (e.g. mass spec, functional assay). False or absent means the protein consequence was predicted from the DNA change. Conventionally encoded in HGVS by parentheses around the p. description.
Reference Transcript
RefSeq transcript accession with version, e.g. 'NM_000059.4'. Stored separately from the HGVS string so that downstream tools can reason about transcript version drift, the most common source of variant ambiguity in clinical handoffs.
Reference Genome Assembly
Reference genome build, e.g. 'GRCh38' or 'GRCh37'. Required when interpreting g.HGVS coordinates.
ClinVar Variation ID
ClinVar VCV accession identifying the variant (not the variant-condition pair). Example: 'VCV000051062' for BRCA2 c.5946delT.
ClinVar RCV ID
ClinVar RCV accession identifying a variant-condition assertion. Multiple RCVs typically attach to one VCV. Lives on VariantInterpretation, not Variant.
dbSNP rsID
NCBI dbSNP reference SNP identifier, e.g. 'rs80359550'. Primary join key for consumer-array (23andMe / AncestryDNA / etc.) imports.
ClinGen Allele Registry CAid
ClinGen Allele Registry canonical allele identifier. Stable across HGVS reformulations and assembly changes — the recommended primary join key when available.
GA4GH VRS Identifier
Deterministic computable hash identifier per GA4GH Variation Representation Spec. Computed from the normalized sequence-location-state object; identical variants always hash to the same VRS ID regardless of how they were originally described.
VRS Allele Object (JSON-LD)
Full VRS Allele JSON-LD payload as serialized string. Carries sequence reference, location interval, and state. Permits round-trip to other VRS-aware systems without re-parsing the HGVS.
Gene Symbol (HGNC Approved)
HGNC approved gene symbol, e.g. 'BRCA2'. Always use the approved symbol, never an alias.
HGNC ID
HGNC numeric identifier with prefix, e.g. 'HGNC:1101' for BRCA2. Stable across symbol changes.
Sequence Ontology Consequence
Sequence Ontology term URI describing the molecular consequence of the variant, e.g. so:0001589 (frameshift_variant), so:0001583 (missense_variant), so:0001587 (stop_gained).
Consequence Label
Human-readable consequence label paired with the SO URI for legibility, e.g. 'frameshift_variant'.
Zygosity
Zygosity of the observed variant. Named-individual values: genomics:Heterozygous, Homozygous, Hemizygous, CompoundHeterozygous, MosaicLow, MosaicHigh. For mosaic variants, also populate genomics:mosaicismFraction with the actual VAF.
Mosaicism Fraction (VAF)
Variant allele fraction (0.0–1.0) for mosaic variants. Distinct from zygosity, which is categorical. The continuous VAF is the load-bearing number for clinical decisions in somatic mosaicism scenarios. NOTE (v1-draft.0.2): for the broader 'fraction of reads supporting alt allele' use genomics:variantAlleleFrequency; mosaicismFraction is reserved for the clinical conclusion that the variant is present in only a subset of cells.
Variant Allele Frequency
Fraction of sequencing reads at the variant position that support the alternate allele. Range 0.0–1.0. Per FHIR Genomics IG LOINC 81258-6. Distinct from genomics:mosaicismFraction — VAF is a sequencing-evidence fraction; mosaicism is the clinical conclusion that the variant is present in only a subset of cells (which often, but not always, manifests as low VAF).
Somatic Status
Whether the variant is germline (inherited / present in all cells) or somatic (acquired / tissue-specific). Critical for cancer interpretation and inheritance reasoning. Per FHIR Genomics IG LOINC 48002-0.
Allelic Phase
For compound heterozygous calls in the same gene: whether the two variants are in cis (same chromosome) or trans (opposite chromosomes). Values: genomics:Cis, Trans, PhaseUnknown. Critical for autosomal recessive inheritance interpretation.
Phased With Variant
Links to the partner Variant when phase has been determined for a compound-heterozygous pair. Symmetric (each variant phasedWith the other).
Haplotype Component Variant
Links a Haplotype to one of its component Variants. A haplotype is composed of multiple variants that travel together on one chromosome.
Star Allele Symbol
PharmVar/HLA-style nomenclature, e.g. 'CYP2C19*2', 'HLA-DQB1*02:01'. The clinically actionable identifier in pharmacogenomics and HLA typing.
Diplotype Notation
Compact paired-haplotype notation, e.g. '*1/*2'. Computed from hapA + hapB; carried as a string for human readability and direct match against PGx guideline tables.
Haplotype A
First haplotype of a diplotype pair. Order (A vs B) is arbitrary but must be stable within a record.
Haplotype B
Second haplotype of a diplotype pair.
Copy Number
Integer copy number observed for the genomic interval, e.g. 1 (heterozygous deletion), 0 (homozygous deletion), 3 (single duplication), 4+ (amplification). Distinct from zygosity.
CNV Interval Start
Start coordinate (1-based, inclusive) of the CNV interval on the reference indicated by cnvIntervalRef.
CNV Interval End
End coordinate (1-based, inclusive) of the CNV interval.
CNV Interval Reference
Genomic reference for the interval coordinates, e.g. 'NC_000013.11' (chromosome 13 in GRCh38) or a chromosome name. Required for downstream analyses to locate the interval.
Variant Interpreted
The Variant being assessed by this VariantInterpretation. SHACL enforces cardinality 1..1 (per D-Q5).
ACMG/AMP Classification
Five-tier ACMG/AMP classification. Named-individual values map 1:1 to LOINC answer codes: Pathogenic (LA6668-3), LikelyPathogenic (LA26332-9), VUS (LA26333-7), LikelyBenign (LA26334-5), Benign (LA6675-8).
ACMG Evidence Criteria
Space-separated ACMG/AMP evidence criteria codes applied in this classification, e.g. 'PVS1 PM2 PP5'. Order is not significant.
Associated Condition
Disease or condition associated with this interpretation. Range is a MONDO/OMIM/ORDO term URI. Per D-Q5, each VariantInterpretation has cardinality 1..1 on this property — multi-condition cases produce multiple interpretation instances.
MONDO Disease ID
MONDO disease ontology ID, e.g. 'MONDO:0007254' for Hereditary breast carcinoma.
OMIM Phenotype/Gene ID
OMIM identifier (six-digit) for a Mendelian phenotype or gene, e.g. '604370' for Breast-ovarian cancer, familial, susceptibility to, 2.
Orphanet Code
Orphanet rare disease code, e.g. 'ORPHA:145' for Hereditary breast and ovarian cancer syndrome.
Mode of Inheritance
GenCC-aligned mode of inheritance for the gene-disease relationship. Named-individual values: AutosomalDominant, AutosomalRecessive, XLinkedDominant, XLinkedRecessive, Mitochondrial, YLinked, MultifactorialPolygenic, UnknownInheritance.
Allelic Requirement
GenCC allelic requirement: monoallelic, biallelic, etc. Captures whether one or two copies of a pathogenic variant are required for the disease phenotype.
Interpreting Laboratory or Expert Panel
Name of the lab, ClinGen Variant Curation Expert Panel (VCEP), or curator who issued this interpretation. Free-text for now; will be replaced with a fhir:Organization reference in v1.0.
Interpretation Date
Date this interpretation was issued. Reclassifications create new Interpretation instances; the date here is the date of THIS classification, not the original.
Submitter Assertion
A single submitter's assertion about a variant-condition pair, e.g. one ClinVar SCV record. Aggregated assertions roll up into a VariantInterpretation via genomics:aggregatedFrom. Individual submissions may disagree with the aggregate (most agree, but ENIGMA, Mayo, Ambry, etc. can each carry distinct opinions).
Aggregated From
Links a VariantInterpretation to the SubmitterAssertions it aggregates. The aggregate classification is computed from these per-submitter records; preserving the constituents lets downstream tools recompute or audit the rollup.
Asserted ACMG Classification
The ACMG class assigned by this individual submitter. May differ from the aggregate classification on the parent VariantInterpretation.
Submitter Name
Name of the submitting laboratory, consortium, or expert panel, e.g. 'ENIGMA', 'Ambry Genetics', 'Mayo Clinic'.
Submitter Organization ID
ClinVar OrgID (or equivalent submitter registry identifier) for the submitting organization.
Submitter Category
Class of submitter: laboratory, consortium, expert-panel, research-group, single-clinician, etc. Drives review-status weighting.
SCV Accession
ClinVar SCV (Submission) accession identifying this individual submission, e.g. 'SCV000123456'.
Contributes to Aggregate
True when this submission is included in the aggregate classification. Some submissions are excluded (withdrawn, superseded, flagged) but retained for audit.
Assertion Evidence Level
Strength-of-evidence label per the submitter's review process. Range is a vocabulary-extensible class — no fixed enum to allow lab-specific gradings.
Review Status
ClinGen / ClinVar review-status classification of this VariantInterpretation, mapping to the 0–4 star confidence rating. Drives advisory engine trust decisions.
Star Rating
Integer 0–4 star rating associated with a ReviewStatus, matching ClinVar UI.
Interpretation Status (Causality)
Whether this variant explains THIS patient's phenotype. Distinct from ACMG classification: ACMG classifies the variant; interpretationStatus classifies the variant's role in the patient's clinical picture. Aligned with GA4GH Phenopackets v2 InterpretationStatus enum.
Genetic Test Type
Test methodology category. Named-individual values: SingleGeneTest, GenePanelTest, ExomeSequencing, GenomeSequencing, ChromosomalMicroarray, KaryotypeAnalysis, MLPA, RepeatExpansionTest, MethylationStudy, RNASequencing.
Gene Panel Members
Space-separated HGNC symbols for the genes included in this test's analytical scope. Used to distinguish 'no variant found in BRCA1/2' from 'no variant found across a 47-gene cancer panel'.
Variants Observed
Variants reported by this test. Empty list with non-empty genePanel = clinically meaningful negative result.
Reported Record
A genomics record (Variant, Haplotype, Diplotype, VariantInterpretation, or other genomics:* class) referenced by this GeneticTest. Use this predicate when the test result is a Diplotype, Haplotype, or PGx implication that has no Variant-typed range. For point-Variant references, prefer the type-specific genomics:variantsObserved (rdfs:range genomics:Variant).
Ordering Provider
Name of clinician who ordered the test. Will become a fhir:Practitioner reference in v1.0.
Performing Laboratory
Name of the laboratory that performed the analysis. Free-text for now; fhir:Organization reference in v1.0.
Ordered At
Timestamp when the test was ordered.
Order Status
Status of the test order: Pending, InProgress, Resulted, Cancelled.
Resulted In
Links a fulfilled GeneticTestOrder to the resulting GeneticTest.
Coverage Depth
Mean coverage depth across the targeted region, e.g. 30.0 for typical clinical WGS. ClinicalGrade tier requires >=30x for WGS or validated panel-specific equivalents.
Sequencing Technology
Sequencing platform/technology category. Named-individual values: ShortReadIllumina, LongReadONT, LongReadPacBio, Mixed, GenotypingArray.
Variant Caller Version
Variant caller name and version, e.g. 'GATK 4.5.0', 'DeepVariant 1.6'. Important for reproducibility and for distinguishing caller-driven differences from biological ones.
Laboratory Certification
Regulatory certification of the performing laboratory. Named-individual values: CLIA, CAP, ISO15189, Uncertified.
Sample Collection Date
Date the biological sample was collected from the patient.
Sequencing Date
Date sequencing was performed on the sample.
File Generation Date
Date the raw genomic file (BAM/CRAM/VCF/etc.) was generated. May post-date sequencingDate by re-alignments or re-calls.
File Format
Raw genomic file format. Named-individual values: BAM, CRAM, FASTQ, gVCF, VCF, BCF, Other. Hot tier (in-pod, encrypted): VCF, gVCF, BCF. Cold tier (out-of-pod, referenced): BAM, CRAM, FASTQ.
File Size (Bytes)
Size of the raw file in bytes. xsd:long because BAM/CRAM/FASTQ files routinely exceed 2^31 bytes (50–100 GB+).
File SHA-256 Hash
Lowercase hex-encoded SHA-256 digest of the file contents. Integrity check enabling the pod to verify the bytes-on-disk match the manifest.
File Location URI
Opaque pointer to where the bytes live (s3://, https://, file://, vendor-specific). Cascade does NOT validate or fetch this URI; the bytes live wherever the user keeps them. See Critical conventions #9.
Reference Genome
Reference assembly the file is aligned against, e.g. 'GRCh38', 'GRCh37', 'T2T-CHM13'. Required for any downstream coordinate-based analysis.
htsget Endpoint
Optional GA4GH htsget endpoint URI for streaming BAM/CRAM regions on demand without ingesting the full file. Letters labs and cloud-genomics services typically expose htsget; consumer providers usually do not.
Genomic Data Provenance
Origin lane of the genomic data, driving importer routing and quality-tier inference. Named-individual values: ConsumerArray, ClinicalSequencing, ResearchSequencing, Imported, AIExtracted. Distinct from the broader cascade:dataProvenance (consumer-vs-clinical classification) — this is genomics-specific because consumer-array imports (Phase 2C) need a distinct lane that auto-tags ConsumerGrade quality.
Data Quality Tier
Quality tier of the genomic data underlying this Variant, driving downstream advisory and narrative subsystems. Named-individual values: ClinicalGrade, ResearchGrade, ConsumerGrade, UnknownQuality. Aligns with cascadeprotocol.org sequencing-provider directory's three quality criteria (>=30x coverage + raw files + CLIA-certified).
Requires Confirmation
True when this VariantInterpretation requires confirmatory clinical-grade re-testing before it can drive care decisions. SHACL (TASK-0.2): any Pathogenic / LikelyPathogenic interpretation MUST either reference a ClinicalGrade Variant OR carry requiresConfirmation true. The advisory engine MUST NOT auto-apply care recommendations to confirmation-required interpretations regardless of issuer trust.
HPO Phenotype Term
Human Phenotype Ontology term identifier, e.g. 'HP:0003002' (Breast carcinoma). Multiple HPO terms per patient or relative are expected.
Phenotype Onset Age
Age in years when the phenotype was first observed. Use HPO onset terms (HP:0011462 Young adult onset, etc.) when only categorical onset is known.
Pedigree
A family pedigree: structured representation of relatives with conditions, ages of onset, and (where available) genotypes. Designed to round-trip with HL7 v3 Family History/Pedigree IG and FHIR FamilyMemberHistory while normalizing to Cascade's three-layer model.
Pedigree Member
A single relative within a pedigree. Distinct from checkup:FamilyHistoryEntry, which is the patient-facing Layer 3 summary; PedigreeMember is the Layer 2 structured record carrying full HPO phenotype set, MONDO disease codes, age of onset/death, sex, and (optionally) carrier or affected status for specific variants.
Proband
The index patient — the family member who brought the family to clinical attention. Required on every Pedigree.
A relative included in the pedigree. Includes the proband.
Relationship to Proband
HL7 v3 RoleCode-aligned relationship, e.g. MTH (mother), FTH (father), SIS (sister), MGRMTH (maternal grandmother). Cardinal relations are first-class; complex relations expressed via nested PedigreeMember chains.
Biological Sex
Biological sex of the relative as relevant to inheritance: 'male', 'female', 'unknown'. Distinct from gender identity, which is not modeled here.
Deceased
Age at Death
Carrier Status for Variant
Tested status of this relative for a specific variant (typically the family's known pathogenic variant). Named-individual values: PositiveAffected, PositiveUnaffected, Negative, NotTested, Obligate.
Tested for Variant
The specific Variant for which this relative's carrierStatus is reported. Allows a relative to have distinct statuses for different variants in the same family.
Pathogenic
Likely Pathogenic
Uncertain Significance
Likely Benign
Benign
Heterozygous
Homozygous
Hemizygous
Compound Heterozygous
Mosaic (low VAF)
Mosaic (high VAF)
Cis (same chromosome)
Trans (opposite chromosomes)
Phase Unknown
Autosomal Dominant
Autosomal Recessive
X-Linked Dominant
X-Linked Recessive
Mitochondrial
Y-Linked
Multifactorial / Polygenic
Unknown Inheritance
Monoallelic
Biallelic
Single Gene Test
Gene Panel
Whole Exome Sequencing
Whole Genome Sequencing
Chromosomal Microarray
Karyotype
MLPA
Repeat Expansion Test
Methylation Study
RNA Sequencing
Positive — Affected
Positive — Unaffected
Negative
Not Tested
Obligate Carrier
Pending
In Progress
Resulted
Cancelled
The index patient who brought the family to clinical attention. Marker, not a kinship relation.
Mother
Father
Sister
Brother
Daughter
Son
Maternal Aunt
Maternal Uncle
Paternal Aunt
Paternal Uncle
Maternal Grandmother
Maternal Grandfather
Paternal Grandmother
Paternal Grandfather
Maternal Cousin
Paternal Cousin
Niece
Nephew
Clinical Laboratory
Consortium
Multi-institution curation consortium (e.g., ENIGMA for BRCA1/2).
Expert Panel
ClinGen Variant Curation Expert Panel (VCEP).
Research Group
Single Clinician
No Assertion Provided
Criteria Not Provided
Single Submitter (criteria provided)
Conflicting Submissions
Multiple Submitters, No Conflict
Expert Panel Reviewed
Practice Guideline
Causative
This variant is the direct cause of the patient's phenotype.
Contributory
This variant contributes to but is not solely responsible for the phenotype.
Uncertain Causality
Causal role is unclear; further investigation needed.
Rejected
This variant has been ruled out as the cause.
Germline
Variant present in the germline; inherited or de novo at conception; present in all cells of the individual.
Somatic
Variant acquired post-conception in a specific tissue / cell lineage; not heritable. Common in tumor samples.
Unknown Somatic Status
Origin not determined by the reporting workflow. Use when the source data is silent on germline-vs-somatic classification rather than guessing.
Short-read Illumina
Illumina short-read sequencing (NovaSeq, NextSeq, etc.). Dominant clinical platform.
Long-read Oxford Nanopore
Oxford Nanopore Technologies long-read sequencing (PromethION, MinION, etc.).
Long-read PacBio HiFi
Pacific Biosciences HiFi/CCS long-read sequencing (Revio, Sequel).
Mixed Technology
Combined short-read + long-read or hybrid sequencing strategies.
Genotyping Array
SNP genotyping array (Illumina Global Screening Array, Affymetrix Axiom, etc.). Used by 23andMe / AncestryDNA / MyHeritage / FTDNA — auto-tagged ConsumerGrade in the importer.
CLIA
Clinical Laboratory Improvement Amendments — US federal regulatory certification of clinical laboratories.
CAP
College of American Pathologists accreditation.
ISO 15189
ISO 15189 medical laboratory accreditation (international).
Uncertified
Laboratory holds no clinical certification (research lab, consumer DTC service).
BAM
Binary Alignment/Map format. Cold tier (out-of-pod, referenced).
CRAM
Compressed Reference-aligned Alignment/Map format. Cold tier.
FASTQ
Raw sequencing reads with quality scores. Cold tier.
gVCF
Genomic VCF — per-position records including reference-confidence blocks. Hot tier.
VCF
Variant Call Format. Hot tier.
BCF
Binary Call Format (binary VCF). Hot tier.
Other
File format not enumerated above (e.g., methylation tracks, structural-variant-specific formats).
Consumer Array
Direct-to-consumer genotyping-array data (23andMe, AncestryDNA, MyHeritage, FTDNA). Phase 2C importer auto-tags every variant from this lane as genomics:ConsumerGrade with genomics:requiresConfirmation true on any pathogenic interpretation.
Clinical Sequencing
Clinical-grade sequencing performed by a CLIA/CAP/ISO15189-certified laboratory.
Research Sequencing
Research-quality sequencing without clinical certification (university cores, biobanks, research consortia).
Imported
Variant data imported from a third-party report, bundle, or pre-existing record where the original sequencing context is incomplete.
AI Extracted
Variant extracted by an LLM from unstructured narrative text (e.g., scanned PDF report). Treat as Imported provenance with elevated confirmation requirement.
Tier classification of the quality of genomic data, used by the advisory engine to gate auto-applied recommendations and by narrative subsystems to drive disclosure language.
Clinical Grade
Sequencing performed by a CLIA-, CAP-, or ISO15189-certified laboratory using a clinical-grade method (>=30x mean coverage WGS, validated clinical panel, or equivalent), with raw files (BAM/CRAM/VCF) retained or accessible. The only tier from which Pathogenic / LikelyPathogenic interpretations may drive auto-applied care recommendations without confirmatory re-testing.
Research Grade
Research-quality sequencing without clinical certification — typical of university cores, biobanks, and research consortia. Adequate for hypothesis generation but requires confirmatory clinical-grade re-testing before driving care decisions.
Consumer Grade
Direct-to-consumer genotyping arrays (23andMe, AncestryDNA, MyHeritage, FTDNA) and consumer DTC sequencing without clinical certification. Genotyping arrays in particular interrogate only ~600k–900k SNP positions and have non-trivial false-positive rates for pathogenic variant calls. ALL Phase 2C consumer-array imports auto-tag this tier; Pathogenic / LikelyPathogenic interpretations on ConsumerGrade variants MUST carry requiresConfirmation true (SHACL-enforced).
Unknown Quality
Quality tier could not be determined from available metadata (no certification, coverage, or method information). Treated as ConsumerGrade by the downstream safety constraint — assume the worst until promoted.
LOINC Code Annotation
LOINC code or answer-list URI annotated on a property or named individual to record its Layer 1 standard mapping.
LOINC Answer Code Annotation
LOINC answer code (LA-prefixed string) for an enumerated value, e.g. LA6668-3 = Pathogenic.
ACMG Classification
Zygosity Value
Allelic Phase Value
Carrier Status
Pedigree Relationship Role
Causality Status
Closed enumeration of variant origin classifications (germline / somatic / unknown). Added in v1-draft.0.2.
Phenotypic Observation
A single HPO-coded phenotypic feature observed in the index patient, captured outside the pedigree/variant context (e.g. during conversational phenotype intake). Supports negated findings (phenotype explicitly absent), essential for narrowing a differential. Provenance is typically cascade:SelfReported. Reuses genomics:hpoTerm for the HPO linkage.
Phenotype Presence Value
Closed enumeration: whether the phenotype is present, absent, or resolved.
Present
Absent
Phenotype explicitly assessed and NOT present (negated finding).
Resolved
Phenotype Presence
Phenotype Onset Date
Calendar date the phenotype was first observed. Use genomics:phenotypeOnsetAge for age-based onset.
Phenotype Severity
Optional HPO severity modifier: mild, moderate, severe, profound (HP:0012823 modifier space).
Phenotype Note