SARS-CoV-2 N Gene G29195T Point Mutation May Affect Diagnostic Reverse Transcription-PCR Detection

Rapid onsite whole-genome sequencing of two suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) N gene diagnostic escape samples revealed a previously unreported N gene point mutation at genome position 29195. Because the G29195T mutation occurs within a region probed by a commonl...

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Published inMicrobiology spectrum Vol. 10; no. 1; p. e0222321
Main Authors Ko, Karrie K K, Abdul Rahman, Nurdyana Binte, Tan, Shireen Yan Ling, Chan, Kenneth X L, Goh, Sui Sin, Sim, James Heng Chiak, Lim, Kun Lee, Tan, Wan Loo, Chan, Kian Sing, Oon, Lynette L E, Nagarajan, Niranjan, Suphavilai, Chayaporn
Format Journal Article
LanguageEnglish
Published United States American Society for Microbiology 23.02.2022
Subjects
Clinical Microbiology
diagnostic escape
G29195T
N gene
Observation
SARS-CoV-2
G29195T
SARS-CoV-2
N gene
diagnostic escape
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Summary:Rapid onsite whole-genome sequencing of two suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) N gene diagnostic escape samples revealed a previously unreported N gene point mutation at genome position 29195. Because the G29195T mutation occurs within a region probed by a commonly referenced U.S. CDC N gene reverse transcription (RT)-PCR assay, we hypothesize that the G29195T mutation rendered the N gene target of a proprietary commercial assay undetectable. The putative diagnostic escape G29195T mutation demonstrates the need for nearly real-time surveillance, as emergence of a novel SARS-CoV-2 variant with the potential to escape diagnostic tests continues to be a threat. Accurate diagnostic detection of SARS-CoV-2 currently depends on the large-scale deployment of RT-PCR assays. SARS-CoV-2 RT-PCR assays target predetermined regions in the viral genomes by complementary binding of primers and probes to nucleic acid sequences in the clinical samples. Potential diagnostic escapes, such as those of clinical samples harboring the G29195T mutation, may result in false-negative SARS-CoV-2 RT-PCR results. The rapid detection and sharing of potential diagnostic escapes are essential for diagnostic laboratories and manufacturers around the world, to optimize their assays as SARS-CoV-2 continues to evolve.
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The authors declare no conflict of interest.
ISSN:2165-0497
2165-0497
DOI:10.1128/spectrum.02223-21