Inflection Genome — Frequently Asked Questions

The Inflection Genome is a rapid whole-genome sequencing (rWGS) test developed to support diagnosis across pediatric care settings. Sequencing uses a blended short-read and long-read approach, with both methodologies performed in parallel to maximize analytical sensitivity and accuracy. Analysis is phenotype-driven, prioritizing variants that contribute to the patient’s reported clinical presentation.

A results report will be returned within four calendar days of sample accession. In a small proportion of cases, this report will be preliminary, pending additional data QC, and a final report will be issued thereafter.

The Inflection Genome is conducted by our lab partner, LSMC (CLIA ID# 05D2347824). Inflection has developed this test in close partnership with LSMC. The lab’s operating systems are linked with those at Inflection, enabling the clinician to track case status within the Inflection Platform (EHR or Web App) for all orders they’ve placed.

Yes. We support proband-only testing, as well as duo and trio configurations with parents.

Yes. Submit a trio test order for each affected sibling and each will receive a report.

Please contact support@inflectionmedicine.com if you are interested in including other or additional first or second-degree relatives as comparators.

The performing laboratory, LSMC, specializes in genome sequencing and does not offer other test types at this time.

The Inflection Genome is a whole-genome assay with phenotype-driven variant prioritization. We do not offer panel-style gene testing. The HPO terms and clinical summary submitted with the order steer what variants are prioritized and considered for reporting.

All orders are placed through the Inflection Platform, either through the EHR or Web App. A licensed clinician must be associated with each order, although a delegated team member may enter the order on their behalf.

To set up an Inflection account for your institution or for assistance with ordering, please contact Inflection Support at support@inflectionmedicine.com.

Standard accepted sample types are EDTA whole blood and buccal swab (Mawi iSWAB-DNA-250). Alternative sample types, such as extracted DNA or saliva, may be accepted on a case-by-case basis. Contact Inflection Support in advance of sample shipment.

• Blood volume: 2 ml preferred, 1 ml minimum
• Blood tube: 13 x 75mm Lavender cap (EDTA)
• Buccal: Refer to instructions provided in the Mawi iSWAB-DNA-250 DNA Collection Kit

Currently, our testing scope is postnatal diagnostic rWGS. We do not accept prenatal specimens or products of conception.

All ordering institutions will be stocked with bulk blood and buccal sample collection kits provided by the laboratory. Collection kits may also be added to individual test orders directly in the Inflection Platform. Kits contain all collection and shipping materials, including a prepaid shipping label. Alternatively, individual kit components (bulk shipping labels and packaging) are available from the lab for in-office collection.

To order buccal kits for home collection of comparator samples, enter the recipient’s shipping address in the Inflection Platform when placing the test order. A complete sample collection kit with instructions and a pre-paid shipping label will be sent directly to the entered address.

EDTA blood should be refrigerated at 4 °C and shipped at ambient temperature within 48 hours of collection.

Buccal swabs should be stored at room temperature and shipped within 60 days of collection.

We only conduct analysis on data generated by our laboratory partner so we can attest to the full analytical chain under their CLIA oversight.

Currently, we accept orders from the US and Canada. Please contact Inflection Support if you are outside of this region and are interested in our services.

Our lab partner operates 7 days per week. Samples can be delivered and accessioned Monday through Saturday.

Contact Inflection Support. We will send a replacement kit at no cost and document the event for carrier follow-up. Do not attempt to use a damaged collection device — specimen integrity cannot be guaranteed.

Our lab partner signs for chain of custody on receipt; carrier proof-of-delivery records are retained. For hospital-to-carrier handoff, please follow your institution’s own chain-of-custody protocol. Every specimen’s accessioning event is timestamped and traceable.

All Inflection Genome cases have a turnaround time of 4 or fewer calendar days; there is no separate, expedited track.

Reports will be issued within 4 days of sample accessioning. Real-time case status is visible in the Inflection Platform for every active order.

HPO terms can be edited (added/removed/changed) in the order anytime up until the interpretation stage of testing. Changes made before that time will be incorporated into analysis and reflected on the report. If the patient’s phenotype changes meaningfully after a report has been issued, consider requesting a reanalysis.

The Inflection Genome combines Illumina short-read and Oxford Nanopore long-read sequencing technologies. More details on this blended approach can be found in Hu et al. 2026.

Most whole genome sequencing is conducted using short-read sequencing alone, which provides deep coverage for reliable variant calling. Long-read sequencing enables detection of variant types that evade detection by short-reads alone, including structural variation, complex rearrangements, and variants in repetitive regions. Hybrid sequencing combines the strengths of each sequencing approach, and further improves the alignment of short reads, resulting in even greater accuracy. Additionally, the hybrid approach offers inherent variant confirmation due to use of dual methodologies in a single assay, reducing the need for orthogonal confirmation and reducing turnaround time.

The Inflection Genome is developed to detect:

• Single nucleotide variants (SNVs) and small insertions/deletions (indels)
• Copy number variation (CNVs)
• Larger structural variants such as deletions, insertions and inversions
• Aneuploidy
• SMN1 and SMN2 copy number
• Mitochondrial DNA variants
• Uniparental disomy (including regions of homozygosity) involving clinically-relevant imprinting regions
• Tri-nucleotide repeat expansions in ARX, PHOX2B, DMPK, ATXN7, FXN, HOXD13, SOX3, and ZIC2 (specific repeat number requires targeted testing)
• Non-coding variants with established clinical significance
• Structural rearrangements may be reported, with analytical limitations noted.

CNVs are called primarily from short-read data with supplementary signal from long-read sequencing for larger and more complex events. Size resolution and handling of variants in segmentally duplicated regions are described in the test specification. Reportable variants in challenging regions will be reported with a stated analytical limitation.

Yes. The mitochondrial genome is sequenced and analyzed as part of the WGS test and does not need to be ordered separately.

Variants are classified following ACMG/AMP guidelines and recommendations from ClinGen (Richards et al. 2015; Riggs et al. 2020; McCormick et al. 2020; SVI WG). Multiple sources are accessed for evidence curation, including ClinVar, gnomAD, in-silico prediction tools, published literature, and internal case data. Interpretation and case sign out are conducted by analysts and licensed laboratory directors, respectively.

Pathogenic, likely pathogenic, and certain variants of uncertain significance involving genes associated with the patient’s reported phenotype are considered reportable. Secondary and incidental findings may be reported (see below for details).

Variants associated with malignant hyperthermia and aminoglycoside-induced ototoxicity in RYR1, CACNA1S, and MT-RNR1 will be reported, even if unrelated to the patient’s reported phenotype. Additionally, chromosome aneuploidy will be reported regardless of overlap with the patient’s reported phenotype. We will not specifically analyze the ACMG secondary findings gene list or otherwise report variants unrelated to the patient’s phenotype that are incidentally discovered.

Evidence used to classify each reported variant is summarized in the genetic report, along with source references.

We do not issue clinical reports for comparators.

New evidence supporting or refuting a reported variant’s clinical significance may emerge after the variant has been reported and may or may not affect its classification. Please contact Inflection Support for guidance on requesting re-curation of a reported variant.

Different laboratories may classify the same variant differently based on how they apply ACMG/AMP variant classification guidelines (Richards et al. 2015), the evidence available at the time of interpretation, and laboratory-specific case data.

Gene-level coverage metrics are available for every case. Contact Inflection Support with the order ID and gene(s) of interest, and we’ll provide the coverage information.

We do not offer targeted variant testing at this time.

If parental testing will clarify the proband’s results (e.g. resolve a VUS or determine phase), parental samples can be added to the initial order in the Inflection Platform up to 7 days after the proband report is issued. Samples must be received by the lab within 30 days. Genome sequencing will be conducted and an updated proband report issued, reflecting the new configuration and any updates to interpretation.

For other family members or to test parents after the 7-day window, we recommend consulting the NIH’s Genetic Testing Registry to find a lab offering targeted testing of the reported variant.

At this time, each test order includes one reanalysis, which can be requested any time after the proband’s initial report is issued.

It is part of Inflection’s vision to enable ongoing variant re-prioritization to support a patient’s care over time. Therefore, this policy will expand in the coming months to support reanalysis in the context of new phenotypic information and/or new indications, such as disease prevention.

This is a whole genome sequencing test in which variants are prioritized based on patient phenotype rather than a gene list or panel. Reported variants have undergone robust quality assessment as part of the standard analysis process. Any variant meeting reporting criteria, including quality metric, will be included on the report, and informal look-backs will not be supported.

If the patient’s phenotype has changed meaningfully since the initial test report was issued, we suggest updating the Clinical Summary and requesting reanalysis through the Inflection Platform.

If you’re interested in exploring variants in the patient that do not meet our criteria for reporting, please consider placing a request for raw data release.

Inflection accommodates requests for raw sequencing data upon request and with family consent. Please contact Inflection Support with your request.

PHI is stored in HIPAA-compliant infrastructure with encryption at rest and in transit. Data is shared only with contracted workflow partners under Business Associate Agreements. Research use of data requires separate opt-in consent. Data is not sold. See our Notice of Privacy Practices for additional details.

Reports only include clinically relevant findings within the test’s reportable range. If you need access to raw variant data, see the raw data request process above.

Physical specimens are retained by our sequencing lab partner under CAP/CLIA baseline policies (approximately 60 days for routine specimens; edge cases per the lab’s retention policy). Sequencing data (raw CRAM and VCF files) is held long-term under our genomic data storage policy. Reports are retained per CLIA/CAP requirements, which are a minimum of 10 years for most states and longer in some jurisdictions.

Please contact Inflection Support by email (support@inflectionmedicine.com) or phone ((774) 229-4004) with questions regarding the Inflection Genome.

To find a lab, we suggest using the NIH’s Genetic Testing Registry.

We do not offer direct-to-consumer ordering or telehealth. We suggest referencing the National Genetic Counselor Directory to find a clinician (in person or via telehealth) who can answer your questions and aid in test ordering, if indicated.

Inflection does not provide pre- or post-test counseling directly to patients. Educational and support resources for families are available through our Family App. Genetic counselors (in-person and telehealth) can be found through the National Genetic Counselor Directory.