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Classification ofPTENgermline non-truncating variants: a new approach to interpretation

Authors: Henri Margot,Natalie Jones,Thibaut Matis,Dominique Bonneau,Tiffany Busa,Françoise Bonnet,Solene Conrad,Louise Crivelli,Pauline Monin,Sandra Fert-Ferrer,Isabelle Mortemousque,Sabine Raad,Didier Lacombe,Frédéric Caux,Nicolas Sevenet,Virginie Bubien,Michel Longy
Publisher: BMJ
Publish date: 2024-10-2
ISSN: 0022-2593,1468-6244 DOI: 10.1136/jmg-2024-109982
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The introduction of a relaxed classification system for PTEN germline variants is a notable advancement. One aspect I found intriguing is how the relaxed criteria adjust the thresholds for variant pathogenicity. Would it be possible to discuss how these adjustments impact clinical decision-making in terms of specific examples from the study?

Another point of curiosity is the clinical utility of this approach. While retrospective data demonstrates promise, could the authors share insights into how this method might be implemented in real-time clinical genetic testing laboratories? For instance, how would such reclassifications affect the current workflows or guidelines?

Lastly, the study raises important questions about patient communication, particularly in cases where a variant previously classified as uncertain is now deemed likely pathogenic. Are there frameworks in place or proposed to manage the implications of such reclassification for genetic counseling?

 

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