The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
Specifications of the ACMG/AMP variant interpretation guidelines for germline TP53 variants
Open accessAbstract
Germline pathogenic variants in TP53 are associated with Li-Fraumeni syndrome, a cancer predisposition disorder inherited in an autosomal dominant pattern associated with a high risk of malignancy, including early-onset breast cancers, sarcomas, adrenocortical carcinomas, and brain tumors. Intense cancer surveillance for individuals with TP53 germline pathogenic variants is associated with reduced cancer-related mortality. Accurate and consistent classification of germline variants across clinical and research laboratories is important to ensure appropriate cancer surveillance recommendations. Here, we describe the work performed by the Clinical Genome Resource TP53 Variant Curation Expert Panel (ClinGen TP53 VCEP) focused on specifying the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) guidelines for germline variant classification to the TP53 gene. Specifications were developed for 20 ACMG/AMP criteria, while nine were deemed not applicable. The original strength level for the 10 criteria was also adjusted due to current evidence. Use of TP53-specific guidelines and sharing of clinical data among experts and clinical laboratories led to a decrease in variants of uncertain significance from 28% to 12% compared with the original guidelines. The ClinGen TP53 VCEP recommends the use of these TP53-specific ACMG/AMP guidelines as the standard strategy for TP53 germline variant classification.
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Richards, S., Aziz, N., Bale, S., Bick, D., Das, S., Gastier-Foster, J., Grody, W. W., Hegde, M., Lyon, E., Spector, E., et al. (2015) · Genetics in Medicine · doi:10.1038/gim.2015.30 · Cited by 32,594
Lane, D. P. (1992) · Nature · doi:10.1038/358015a0 · Cited by 5,138
ClinVar: improving access to variant interpretations and supporting evidence
Landrum, M. J., Lee, J. M., Benson, M., Brown, G. R., Chao, C., Chitipiralla, S., Gu, B., Hart, J., Hoffman, D., Jang, W., et al. (2018) · Nucleic Acids Research · doi:10.1093/nar/gkx1153 · Cited by 4,196 · cited 3×
“Consistent with the ClinGen VCEP process, all of the TP53 classified variants have been submitted to the ClinVar database (Landrum et al., 2018) with a summary of the classification process.”
MethodResultInfluentialTP53 mutations in human cancers: origins, consequences, and clinical use.
Olivier, M., Hollstein, M., & Hainaut, P. (2010) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a001008 · Cited by 2,199 · cited 2×
“(Caron et al., 2016; Kratz et al., 2017; Olivier et al., 2010), the criteria were specified based only on the number of meioses of any LFS‐associated cancer type, and the number of families reported.”
BackgroundSelf-citationWhen mutants gain new powers: News from the mutant p53 field
Brosh, R., & Rotter, V. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2693 · Cited by 1,132
Revisiting Li-Fraumeni Syndrome From TP53 Mutation Carriers
Bougeard, G., Renaux-Petel, M., Flaman, J.-M., Charbonnier, C., Fermey, P., Belotti, M., Gauthier-Villars, M., Stoppa-Lyonnet, D., Consolino, E., Brugières, L., et al. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2014.59.5728 · Cited by 760
Modeling the ACMG/AMP variant classification guidelines as a Bayesian classification framework
Tavtigian, S. V., Greenblatt, M. S., Harrison, S. M., Nussbaum, R. L., Prabhu, S. A., Boucher, K. M., & Biesecker, L. G. (2018) · Genetics in Medicine · doi:10.1038/gim.2017.210 · Cited by 590
Mutational processes shape the landscape of TP53 mutations in human cancer
Giacomelli, A. O., Yang, X., Lintner, R. E., McFarland, J. M., Duby, M., Kim, J., Howard, T. P., Takeda, D. Y., Ly, S. H., Kim, E., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0204-y · Cited by 556
Villani, A., Shore, A., Wasserman, J. D., Stephens, D., Kim, R. H., Druker, H., Gallinger, B., Naumer, A., Kohlmann, W., Novokmet, A., et al. (2016) · The Lancet Oncology · doi:10.1016/s1470-2045(16)30249-2 · Cited by 546
Using high-resolution variant frequencies to empower clinical genome interpretation
Whiffin, N., Minikel, E., Walsh, R., O’Donnell-Luria, A. H., Karczewski, K., Ing, A. Y., Barton, P. J. R., Funke, B., Cook, S. A., MacArthur, D., et al. (2017) · Genetics in Medicine · doi:10.1038/gim.2017.26 · Cited by 441 · cited 2×
“(Whiffin et al., 2017).”
Method
Cited by
ClinVar: updates to support classifications of both germline and somatic variants
Landrum, M. J., Chitipiralla, S., Kaur, K., Brown, G., Chen, C., Hart, J., Hoffman, D., Jang, W., Liu, C., Maddipatla, Z., et al. (2025) · Nucleic Acids Research · doi:10.1093/nar/gkae1090 · Cited by 182
Tejura, M., Fayer, S., McEwen, A. E., Flynn, J., Starita, L. M., & Fowler, D. M. (2024) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2024.07.018 · Cited by 35
Dawood, M., Fayer, S., Pendyala, S., Post, M., Kalra, D., Patterson, K., Venner, E., Muffley, L. A., Fowler, D. M., Rubin, A. F., et al. (2024) · Genome Medicine · doi:10.1186/s13073-024-01392-7 · Cited by 31
Self-citationMontellier, E., Lemonnier, N., Penkert, J., Freycon, C., Blanchet, S., Amadou, A., Chuffart, F., Fischer, N. W., Achatz, M.-I., Levine, A. J., et al. (2024) · iScience · doi:10.1016/j.isci.2024.111296 · Cited by 29
Allen, S., Garrett, A., Muffley, L., Fayer, S., Foreman, J., Adams, D. J., Hurles, M., Rubin, A. F., Roth, F. P., Starita, L. M., et al. (2024) · European Journal of Human Genetics · doi:10.1038/s41431-024-01566-2 · Cited by 17
Metadata
- Authors
- Fortuno, C., Lee, K., Olivier, M., Pesaran, T., Mai, P. L., Andrade, K. C., Attardi, L. D., Crowley, S., Evans, D. G., Feng, B., Foreman, A. K. M., Frone, M. N., Huether, R., James, P. A., McGoldrick, K., Mester, J., Seifert, B. A., Slavin, T. P., Witkowski, L., Zhang, L., Plon, S. E., Spurdle, A. B., Savage, S. A., & Panel, T. C. T. V. C. E.
- Venue
- Human Mutation
- Publisher
- Wiley
- Published
- 2020-12-25
- Volume
- 42
- Issue
- 3
- Pages
- 223-236
- ISSN
- 1059-7794 (ISSN-L)
- 1098-1004
- OpenAlex
- W3111162271
- Cited by
- 167
- References
- 11
- FWCI
- 9.55
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Fortuno, C., Lee, K., Olivier, M., Pesaran, T., Mai, P. L., Andrade, K. C., Attardi, L. D., Crowley, S., Evans, D. G., Feng, B., Foreman, A. K. M., Frone, M. N., Huether, R., James, P. A., McGoldrick, K., Mester, J., Seifert, B. A., Slavin, T. P., Witkowski, L., . . . Panel, T. C. T. V. C. E. (2021). Specifications of the ACMG/AMP variant interpretation guidelines for germline TP53 variants. Human Mutation. https://doi.org/10.1002/humu.24152
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