Journal article

A quantitative model to predict pathogenicity of missense variants in the TP53 gene

Cristina Fortuno, Arcadi Cipponi, Mandy L Ballinger, Sean Tavtigian, Magali Olivier, Vatsal Ruparel, Ygal Haupt, Sue Haupt, Kathy Tucker, Amanda B Spurdle, David M Thomas, Paul A James

HUMAN MUTATION | WILEY | Published : 2019


Germline pathogenic variants in the TP53 gene cause Li-Fraumeni syndrome, a condition that predisposes individuals to a wide range of cancer types. Identification of individuals carrying a TP53 pathogenic variant is linked to clinical management decisions, such as the avoidance of radiotherapy and use of high-intensity screening programs. The aim of this study was to develop an evidence-based quantitative model that integrates independent in silico data (Align-GVGD and BayesDel) and somatic to germline ratio (SGR), to assign pathogenicity to every possible missense variant in the TP53 gene. To do this, a likelihood ratio for pathogenicity (LR) was derived from each component calibrated using..

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Awarded by National Health and Medical Research Council

Awarded by Cancer Institute NSW

Awarded by National Cancer Institute

Funding Acknowledgements

National Health and Medical Research Council, Grant/Award Numbers: 1104364, 10004017, 1061778; Cancer Institute NSW, Grant/Award Number: CDF171109; National Cancer Institute, Grant/Award Number: CA164944; Rainbows for Kate Foundation; Australian National Health and Medical Research Council; Johanna Sewell Research Foundation; Australasian Sarcoma Study Group