MAUDE Adverse Event Report: SEQUENCING INC. GENOME DISCOVERY WGS BUNDLE; GENETIC VARIANT DETECTION AND HEALTH RISK ASSESSMENT SYSTEM

Health Effect - Clinical Code	Insufficient Information (4580)
Date of Event	08/02/2024
Type of Reportable Event	Malfunction
Event or Problem Description
Hello.I am a phd clinical genetics and genomics expert.A genetic counselor just made me aware of an ivd offered as an ldt that she saw advertised online that is highly suspect for both false positives and false negatives.It's a whole genome sequencing test called "sequencing.Com", see https://sequencing.Com/.It reports on health, rare disease, wellness, and family findings.Page https://sequencing.Com/rare-disease-dna-analysis-list?page=1 lists thousands of genetic conditions and says, "sequencing's next generation rare disease screen v3 provides a single, comprehensive analysis of more than 17,000 diseases, conditions, and traits." after just a quick review of the test on the website i have two major concerns: 1) the ldt is not following best practices for clinical variant classification and report generation and is likely reporting many false positive and false negative variant classifications in clinically important genes.2) the ldt is presenting itself on its website as if it's direct-to-consumer when it has not received fda premarket approval, and therefore has no verified special controls required for dtc ivds.I can't find the clia # on their website for where the sequencing part of the test is done.However, a picture in this detailed product review https://www.Dnaweekly.Com/reviews/sequencing-com/, taken at an unknown date, showed that the saliva collection kit was branded by "living dna" and was mailed to akesogen, 3155 northwoods pl nw, peachtree corners, ga 30071.Akesogen seems to have closed, but the address now has a clia certificate held by tempus ai, inc, clia # 11d2050537 (effective 09/27/2023 - 09/26/2025).(note that this is not the same tempus location running cdx tests, which is in chicago).I suspect that sequencing.Com does their own data processing and report generation.A member of the two-person leadership team was previously a scientist at the nih's ncbi, the division of the nih that developed clinvar.This brings me to my concern that the ldt is likely not following best practices for variant classification and reporting.This page describes the company's disease-specific results reporting approach: https://sequencing.Com/knowledge-center/faqs/guide-disease-specific-results-next-gen-screening.I suspect that the company has simply made a web interface pulling from research-use-only variant classification databases, primarily clinvar, and is using clinvar's "review status" star rating system for variant classifications to allow the patient/consumer to toggle the confidence level of the clinvar classifications between "all" or "high only".But clinvar and other research-use-only variant classification databases are rife with poorly done variant classifications, and the databases are nowhere near exhaustive.Which is why protocols based on the variant classifications standards and guidelines set by acmg, amp, cap, and clingen require time-consuming and often very manual variant classification procedures to reduce both false positive and false negative classifications.Sequencing.Com does not appear to be following such protocols since they seem extremely automated.And they're not just using clinvar "expert panel" fda approved variant classifications, since they report variants in thousands more genes than there are fda approved expert gene-disease classification panels.I strongly suspect that sequencing.Com has very few, if any, quality control measures in place to ensure the accuracy of the variant classifications they report.I also suspect that the format and oversight of their ever-changeable report (https://sequencing.Com/knowledge-center/faqs/guide-disease-specific-results-next-genscreening) is not even following clia regulations for test reports (https://www.Ecfr.Gov/current/title-42/chapter-iv/subchapter-g/part-493/subpart-k/subject-group).In summary, i believe sequencing.Com is passing off a research-use only product as an ldt and is presenting it on its website like a dtc ivd.Sequencing.Com.Whole genome sequencing bundle.

• Brand Name: GENOME DISCOVERY WGS BUNDLE
• Common Device Name: GENETIC VARIANT DETECTION AND HEALTH RISK ASSESSMENT SYSTEM
• Manufacturer (Section D): SEQUENCING INC.; 680 e colorado blvd.; suite 180; pasadena CA 91101
• MDR Report Key: 19961742
• Report Number: MW5158298
• Device Sequence Number: 8402089
• Product Code: PTA
• Combination Product (Y/N): N
• Initial Reporter State: UT
• Initial Reporter Country: US
• Number of Events Summarized: 1
• Summary Report (Y/N): N
• Reporter Type: Voluntary
• Initial Reporter Occupation: Other Health Care Professional
• Type of Report: Initial
• Report Date (Section B): 08/02/2024

1 Device was Involved in the Event

1 Patient was Involved in the Event

• Is this an Adverse Event Report?: No
• Is this a Product Problem Report?: Yes
• Was Device Available for Evaluation?: No
• Initial Date Received by Manufacturer: Not provided
• Initial Report FDA Received Date: 08/09/2024
• Patient Sequence Number: 1
• Patient Sex: Unknown