Synonymous Variants of Uncertain Silence
Synonymous variants, traditionally regarded as silent mutations due to their lack of impact on protein sequence, structure and function, have been the subject of increasing scrutiny. This commentary explores the emerging evidence challenging the notion of synonymous variants as functionally inert. A...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-06-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/13/10556 |
| _version_ | 1797591661222559744 |
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| author | Christopher J. Giacoletto Jerome I. Rotter Wayne W. Grody Martin R. Schiller |
| author_facet | Christopher J. Giacoletto Jerome I. Rotter Wayne W. Grody Martin R. Schiller |
| author_sort | Christopher J. Giacoletto |
| collection | DOAJ |
| description | Synonymous variants, traditionally regarded as silent mutations due to their lack of impact on protein sequence, structure and function, have been the subject of increasing scrutiny. This commentary explores the emerging evidence challenging the notion of synonymous variants as functionally inert. Analysis of the activity of 70 synonymous variants in the HIV Tat transcription factor revealed that 50% of the variants exhibited significant deviations from wild-type activity. Our analysis supports previous work and raises important questions about the broader impact of non-silent synonymous variants in human genes. Considering the potential functional implications, the authors propose classifying such variants as “synonymous variants of uncertain silence” (sVUS), highlighting the need for cautious interpretation and further investigations in clinical and genetic testing settings. |
| first_indexed | 2024-03-11T01:40:27Z |
| format | Article |
| id | doaj.art-d6cb7298f93b4359a495ce307e91db8a |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T01:40:27Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d6cb7298f93b4359a495ce307e91db8a2023-11-18T16:39:57ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-06-0124131055610.3390/ijms241310556Synonymous Variants of Uncertain SilenceChristopher J. Giacoletto0Jerome I. Rotter1Wayne W. Grody2Martin R. Schiller3Nevada Institute of Personalized Medicine, University of Nevada Las Vegas, 4505 S. Maryland Parkway, Las Vegas, NV 89154, USAHeligenics Inc., 10530 Discovery Drive, Las Vegas, NV 89135, USADepartment of Pathology and Laboratory Medicine, University of California Los Angeles School of Medicine, 10833 Le Conte Ave., 705, Los Angeles, CA 90095, USANevada Institute of Personalized Medicine, University of Nevada Las Vegas, 4505 S. Maryland Parkway, Las Vegas, NV 89154, USASynonymous variants, traditionally regarded as silent mutations due to their lack of impact on protein sequence, structure and function, have been the subject of increasing scrutiny. This commentary explores the emerging evidence challenging the notion of synonymous variants as functionally inert. Analysis of the activity of 70 synonymous variants in the HIV Tat transcription factor revealed that 50% of the variants exhibited significant deviations from wild-type activity. Our analysis supports previous work and raises important questions about the broader impact of non-silent synonymous variants in human genes. Considering the potential functional implications, the authors propose classifying such variants as “synonymous variants of uncertain silence” (sVUS), highlighting the need for cautious interpretation and further investigations in clinical and genetic testing settings.https://www.mdpi.com/1422-0067/24/13/10556synonymous variantsilent variantsequencevariant interpretation |
| spellingShingle | Christopher J. Giacoletto Jerome I. Rotter Wayne W. Grody Martin R. Schiller Synonymous Variants of Uncertain Silence International Journal of Molecular Sciences synonymous variant silent variant sequence variant interpretation |
| title | Synonymous Variants of Uncertain Silence |
| title_full | Synonymous Variants of Uncertain Silence |
| title_fullStr | Synonymous Variants of Uncertain Silence |
| title_full_unstemmed | Synonymous Variants of Uncertain Silence |
| title_short | Synonymous Variants of Uncertain Silence |
| title_sort | synonymous variants of uncertain silence |
| topic | synonymous variant silent variant sequence variant interpretation |
| url | https://www.mdpi.com/1422-0067/24/13/10556 |
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