Partial ORF1ab Gene Target Failure with Omicron BA.2.12.1

Yale SARS-CoV-2 Genomic Surveillance Initiative

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Mutations in the genome of SARS-CoV-2 can affect the performance of molecular diagnostic assays. In some cases, such as S-gene target failure, the impact can serve as a unique indicator of a particular SARS-CoV-2 variant and provide a method for rapid detection. Here, we describe partial ORF1ab gene target failure (pOGTF) on the cobas SARS-CoV-2 assays, defined by a $2-thermocycle delay in detection of the ORF1ab gene compared to that of the E-gene. We demonstrate that pOGTF is 98.6% sensitive and 99.9% specific for SARS-CoV-2 lineage BA.2.12.1, an emerging variant in the United States with spike L452Q and S704L mutations that may affect transmission, infectivity, and/ or immune evasion. Increasing rates of pOGTF closely mirrored rates of BA.2.12.1 sequences uploaded to public databases, and, importantly, increasing local rates of pOGTF also mirrored increasing overall test positivity. Use of pOGTF as a proxy for BA.2.12.1 provides faster tracking of the variant than whole-genome sequencing and can benefit laboratories without sequencing capabilities.

Original languageEnglish
JournalJournal of clinical microbiology
Issue number6
StatePublished - Jun 2022


  • ORF1ab gene
  • RT-PCR
  • SARS-CoV-2
  • cycle threshold (CT) value
  • partial ORF1ab gene target failure (pORF1ab)
  • whole-genome sequencing (WGS)


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