Clinical Decision Support · Not SaMD · Geneticist Sign-Off Required

Vendor-neutral
ACMG interpretation
in minutes, not hours.

VariantIQ ingests any VCF and returns a clinician-ready, ACMG/AMP-compliant interpretive report — deterministic rules engine, bounded NLP evidence extraction, complete CAP/CLIA audit trail. The geneticist reviews and signs. VariantIQ eliminates the 2-hour literature search.

✓ CAP/CLIA-ready audit trail

✓ Vendor-neutral · any sequencer

✓ No generative classification

✓ FHIR R4 + PDF export

VariantIQ

Engine v2.4.1 · ACMG 2023

MYH7 — Hypertrophic Cardiomyopathy

NM_000257.4:c.1208G>A (p.Arg403Gln)

Variant of Uncertain Significance

Score: +6 / LP threshold +8

ACMG/AMP Criteria

PS4 Prevalence in affected > controls MET · Strong PMID 34025432

PM1 Mutational hotspot / domain MET · Moderate PMID 29493581

PP3 Computational: REVEL 0.88 MET · Supporting REVEL/CADD

PP1 Co-segregation data INSUFFICIENT No data

ⓘ Evidence extracted by bounded NLP from PubMed · All PMIDs validated via API · Geneticist review required before finalization

Illustrative sample only — not for clinical use. Geneticist sign-off required before any report is finalized.

The Problem

40–70% VUS. Hours of curation. And every capable tool is now sequencer-captive.

Clinical molecular geneticists spend 2–4 hours per complex case on manual literature search, ACMG criteria application, and documentation — before any clinical insight is delivered. At the same time, every capable automated interpretation platform has been acquired by a sequencer manufacturer.

Emedgene was acquired by Illumina. Fabric by GeneDx. Genoox by QIAGEN. Labs that run Illumina and PacBio and Oxford Nanopore have no independent interpretation layer — just spreadsheets and in-house curation.

Pathogenic → Likely Pathogenic → VUS → Likely Benign → Benign

ACMG/AMP 5-tier classification framework — all 28 criteria applied deterministically by VariantIQ's rules engine.

📑

Manual literature review is the bottleneck

Board-certified geneticists spend the majority of case time on PubMed searches, ClinVar reviews, and evidence documentation — work a deterministic rules engine can assist in minutes.

2–4 hours per complex VUS case

❓

VUS management is unsolved at scale

40–70% of variants in complex panels are classified as VUS. Without cross-institutional evidence aggregation, the same variant is re-evaluated independently at every lab — with no shared learning.

40–70% VUS rate in rare disease panels

🔒

Every capable platform is now sequencer-locked

Acquisition by hardware manufacturers means interpretation software is bundled with sequencer contracts. Multi-vendor labs — the fastest-growing segment — have no independent option.

Emedgene · Fabric · Genoox — all acquired

How It Works

VCF in. Clinician-ready report out. Geneticist signs off.

Four deterministic steps — no black-box AI, full audit trail at every stage.

VCF Ingestion & Normalization

Any VCF (v4.1–4.3) from any sequencer. Left-aligned, decomposed, annotated against GRCh37/38. MANE Select transcript, HGVS nomenclature. Processed within 5 minutes.

Vendor-neutral · any pipeline

Deterministic ACMG/AMP Rules Engine

All 28 ACMG/AMP criteria applied deterministically. ClinVar, gnomAD v4, OMIM integrated. Each criterion independently auditable with evidence source citation and rules engine version pinned.

No generative AI in classification

Bounded NLP Evidence Extraction

Structured evidence retrieved from PubMed and ClinVar. Every PMID validated via API before display. Original passage shown for human verification. NLP output is evidence display — never automatic classification.

Every claim audited to source

Geneticist Review & Sign-Off

The geneticist reviews criteria, reads evidence, accepts or overrides with documented rationale. Override logged immutably. PDF and FHIR R4 report generated only after geneticist attestation.

CAP/CLIA audit trail · FHIR export

Platform Features

Built for CLIA-certified labs, from the ground up.

Every feature is designed to support CAP/CLIA compliance, geneticist productivity, and vendor-neutral interoperability.

⚙

Deterministic ACMG/AMP Engine

All 28 criteria (PVS1, PS1–4, PM1–6, PP1–5, BA1, BS1–4, BP1–7) applied by a versioned, auditable rules engine. ClinGen SVI refinements included. Zero generative AI in the classification path.

Rules Engine v2.4.1 · ACMG 2023 + ClinGen SVI

📚

Bounded NLP with Provenance

PubMed literature extraction returns structured fields: variant ID, functional impact, population frequency, co-segregation. Every claim includes PMID, confidence score, and original passage for verification.

Hallucination guard · PMID API validation

📊

VUS Resolver — Multi-Lab Intelligence

Cross-institutional VUS evidence aggregation. When the same variant appears across two or more contributing labs, aggregate evidence is synthesized monthly. Variants approaching reclassification thresholds are surfaced for expedited review.

Data moat · monthly retraining cycle

🔗

Vendor-Neutral by Design

Works downstream of any sequencer (Illumina, PacBio, Oxford Nanopore) and any LIMS. LabWare integration at launch; StarLIMS and Orchard adapters in months 6–9. HL7 v2 and REST API.

LabWare MVP · StarLIMS / Orchard V1.1

📋

CAP/CLIA-Ready Architecture

Immutable audit log for every system action — ingestion, annotation, criterion evaluation, evidence retrieval, geneticist decision, report generation. Each log entry timestamped with user/system identity and input/output hash.

10-year retention · CLIA §493.1253

📄

FHIR R4 + PDF Report Export

Clinician-ready PDF conforming to ACMG report guidelines, generated only after geneticist sign-off. FHIR R4 DiagnosticReport for EHR integration. Draft reports watermarked "DRAFT — NOT FOR CLINICAL USE" until attestation.

FHIR R4 · ACMG report standard

Validation & Credibility

The concordance study is the sales document.

Before commercial launch, VariantIQ is validated against 500 historical cases reviewed by board-certified geneticists. The targets below represent our commercial launch criteria.

Data below are illustrative performance targets for the concordance validation study, not yet commercially available results.

96.4%

Overall concordance with board-certified geneticists

Measured across all 5 ACMG classification tiers on a 500-case retrospective cohort of germline rare-disease variants.

Illustrative target — not yet commercially validated

Concordance by Classification Tier

Pathogenic 98.1% agreement

Likely Pathogenic 96.3% agreement

VUS 94.8% agreement

Likely Benign 97.2% agreement

Benign 99.0% agreement

Illustrative targets · 500-case retrospective concordance study · Not yet commercially validated

Validation Study Design

Metric	Target	Status
Overall concordance	≥ 95%	✓ Target
Critical discordances (P↔B)	0	✓ Required
VUS rate vs. human baseline	≤ baseline + 5%	✓ Target
Case turnaround time	< 15 minutes	✓ Target
Cohort size	500 cases	In progress
CAP/CLIA validation docs	CLSI AUTO10-A	In progress

🎯 The Retrospective Concordance Pilot

Submit 500 of your historical, classified cases. VariantIQ re-classifies them and we compare the results side-by-side with your geneticists' determinations — at no cost. The concordance report is your purchase decision.

No platform commitment required. Results delivered in 2–4 weeks.

Pricing

Per-report pricing. No platform lock-in.

Volume commitments earn 15% annual discount. White-label API pricing available for reference labs and platform partners.

Germline

^$18–28_/report

Rare disease germline SNV and small indel classification. Carrier screening. Reproductive panels.

All 28 ACMG/AMP criteria
ClinVar + gnomAD + OMIM integration
NLP evidence extraction with provenance
VUS Resolver access
PDF + FHIR R4 export
CAP/CLIA audit trail
LabWare LIMS integration

Somatic / Oncology

^$35–55_/report

Tumor profiling and somatic variant classification. AMP/ASCO/CAP Tier I–IV framework. V2 — months 9–18.

AMP/ASCO/CAP somatic tiers
Tumor mutational burden analysis
MSI status integration
Oncology knowledge bases
Targeted therapy associations (CDS only)
PDF + FHIR R4 export
Full audit trail

Pharmacogenomics

^$10–15_/report

PGx diplotype calling and CPIC guideline-level evidence synthesis. V2 — months 9–18.

CPIC guideline integration
Diplotype → phenotype mapping
Key PGx gene panel coverage
FHIR MedicationStatement export
CAP/CLIA audit trail

Volume commitments (annual): 15% discount. Enterprise / white-label API: $0.50–1.00 per call.
A 300-report/month germline lab at $25/report = $90K ARR. Alternative: 1.5 FTE geneticists at $300K+ fully loaded.

FAQ

Common questions from lab directors and clinical geneticists.

Is VariantIQ making the clinical diagnosis? Does the geneticist actually need to review?

No. VariantIQ is Clinical Decision Support — the platform surfaces evidence and proposes a classification based on the deterministic ACMG/AMP rules engine. A board-certified geneticist reviews every case, accepts or overrides the recommendation, documents their rationale, and signs the report. No report is generated without geneticist attestation.

Does VariantIQ use generative AI to classify variants?

No. Classification uses a deterministic rules engine applying all 28 ACMG/AMP criteria. A bounded NLP model is used only for structured literature extraction from PubMed — extracting evidence fields (variant ID, functional impact, co-segregation data) that are then displayed to the reviewing geneticist. LLM output never modifies a classification directly. All cited PMIDs are validated against the PubMed API before display.

We use multiple sequencers — Illumina for germline and Oxford Nanopore for rapid TAT. Does VariantIQ work with both?

Yes. VariantIQ ingests standard VCF files (v4.1–4.3) regardless of sequencer or upstream bioinformatics pipeline. The platform normalizes and annotates against GRCh37 and GRCh38. Vendor-neutral by design — this is the core architectural thesis.

How does VariantIQ handle CAP/CLIA audit requirements?

Every system action generates an immutable audit log entry: timestamp, user/system identity, action type, input hash, output hash, and rules engine version. Logs are exportable in JSON and CSV for CAP/CLIA inspectors. Rules engine version is pinned to each case record — a re-analysis with a newer engine creates a new case version. 10-year retention, configurable per lab policy.

What LIMS systems does VariantIQ integrate with?

LabWare LIMS v8+ is the MVP integration (bidirectional, HL7 v2 and REST API, target setup <2 weeks). StarLIMS and Orchard adapters are on the V1.1 roadmap (months 6–9). FHIR R4 export is available from day one for EHR-adjacent integrations.

What is the VUS Resolution Database and how does privacy work?

The VUS Resolution Database aggregates de-identified variant classification data across contributing CLIA labs. Only anonymized, aggregated evidence is shared — each lab's patient data remains logically isolated. When the same variant is observed at two or more labs, the system synthesizes cross-institutional evidence monthly and flags variants approaching reclassification thresholds for expedited review.

Is VariantIQ FDA-cleared?

VariantIQ is positioned as a Clinical Decision Support tool, not a software-as-a-medical-device (SaMD). The geneticist reviews and signs all reports; the platform does not make autonomous clinical decisions. The architecture is designed from day one to support a future De Novo SaMD submission if the regulatory environment requires it.

What does the concordance pilot actually involve?

You provide 500 historical, already-classified germline cases (de-identified). VariantIQ re-classifies each case independently and delivers a side-by-side concordance report comparing our output to your geneticists' determinations. No platform commitment is required. The concordance report is your purchase decision document. Typical turnaround: 2–4 weeks.

Get Started

Request a concordance study.
Let the data decide.

Submit 500 historical cases. We re-classify them using the VariantIQ deterministic rules engine and return a side-by-side concordance report — at no cost, with no platform commitment. If we hit 95% concordance with zero critical discordances, you have everything you need to make the decision.

VariantIQ is a Clinical Decision Support tool. All interpretive reports require geneticist review and sign-off before clinical use. VariantIQ does not make autonomous clinical diagnoses or treatment recommendations. Sample data throughout this site is illustrative only.

Vendor-neutral ACMG interpretation in minutes, not hours.