Villani Rehan M, Terrill Bronwyn, Tudini Emma, McKenzie Maddison E, Cliffe Corrina C, Hahn Christopher N, Lundie Ben, Mattiske Tessa, Matotek Ebony, McEwen Abbye E, Nickerson Sarah L, Breen James, Fowler Douglas M, Christodoulou John, Starita Lea, Rubin Alan F, Spurdle Amanda B
QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Australian Genomics, Murdoch Children's Research Institute, Melbourne, Australia.
medRxiv. 2024 Dec 6:2024.12.04.24318523. doi: 10.1101/2024.12.04.24318523.
To determine if a variant identified by diagnostic genetic testing is causal for disease, applied genetics professionals evaluate all available evidence to assign a clinical classification. Experimental assay data can provide strong functional evidence for or against pathogenicity in variant classification, but appears to be underutilised. We surveyed genetic diagnostic professionals in Australasia to assess their application of functional evidence in clinical practice. Results indicated that survey respondents are not confident to apply functional evidence, mainly due to uncertainty around practice recommendations. Respondents also identified need for support resources, educational opportunities, and in particular requested expert recommendations and updated practice guidelines to improve translation of experimental data to curation evidence. As an initial step, we have collated a list of functional assays recommended by 19 ClinGen Variant Curation Expert Panels as a source of international expert opinion on functional evidence evaluation. Additional support resources for diagnostic practice are in development.
为了确定诊断性基因检测所鉴定的变异是否为疾病的病因，应用遗传学专业人员会评估所有可用证据以进行临床分类。实验检测数据可为变异分类中的致病性提供有力的支持或反对证据，但似乎未得到充分利用。我们对澳大拉西亚地区的基因诊断专业人员进行了调查，以评估他们在临床实践中对功能证据的应用情况。结果表明，参与调查的受访者对应用功能证据缺乏信心，主要原因是实践建议存在不确定性。受访者还指出需要支持资源、教育机会，尤其请求提供专家建议和更新的实践指南，以改善从实验数据到整理证据的转化。作为第一步，我们整理了19个临床基因组学变异整理专家小组推荐的功能检测列表，作为关于功能证据评估的国际专家意见来源。针对诊断实践的其他支持资源正在开发中。
