Richards C Sue, Bale Sherri, Bellissimo Daniel B, Das Soma, Grody Wayne W, Hegde Madhuri R, Lyon Elaine, Ward Brian E
Department of Molecular and Medical Genetics, Oregon Health Science University, Portland, Oregon 97239, USA.
Genet Med. 2008 Apr;10(4):294-300. doi: 10.1097/GIM.0b013e31816b5cae.
ACMG previously developed recommendations for standards for interpretation of sequence variations. We now present the updated revised recommendations. Here, we describe six interpretative categories of sequence variations: (1) sequence variation is previously reported and is a recognized cause of the disorder; (2) sequence variation is previously unreported and is of the type which is expected to cause the disorder; (3) sequence variation is previously unreported and is of the type which may or may not be causative of the disorder; (4) sequence variation is previously unreported and is probably not causative of disease; (5) sequence variation is previously reported and is a recognized neutral variant; and (6) sequence variation is previously not known or expected to be causative of disease, but is found to be associated with a clinical presentation. We emphasize the importance of appropriate reporting of sequence variations using standardized terminology and established databases, and of clearly reporting the limitations of sequence-based testing. We discuss follow-up studies that may be used to ascertain the clinical significance of sequence variations, including the use of additional tools (such as predictive software programs) that may be useful in variant classification. As more information becomes available allowing the interpretation of a new sequence variant, it is recommended that the laboratory amend previous reports and provide updated results to the physician. The ACMG strongly recommends that the clinical and technical validation of sequence variation detection be performed in a CLIA-approved laboratory and interpreted by a board-certified clinical molecular geneticist or equivalent.
美国医学遗传学与基因组学学会（ACMG）此前制定了序列变异解读标准的建议。我们现在公布更新后的修订建议。在此，我们描述序列变异的六种解读类别：（1）序列变异先前已被报道，且是该疾病的公认病因；（2）序列变异先前未被报道，且属于预期会导致该疾病的类型；（3）序列变异先前未被报道，且属于可能是或可能不是该疾病病因的类型；（4）序列变异先前未被报道，且可能不是疾病的病因；（5）序列变异先前已被报道，且是公认的中性变异；（6）序列变异先前未知或预期不是疾病的病因，但被发现与临床表现相关。我们强调使用标准化术语和既定数据库适当报告序列变异的重要性，以及清楚报告基于序列检测的局限性。我们讨论了可用于确定序列变异临床意义的后续研究，包括使用可能有助于变异分类的其他工具（如预测软件程序）。随着有更多信息可用于解读新的序列变异，建议实验室修改先前的报告并向医生提供更新的结果。ACMG强烈建议在经临床实验室改进修正案（CLIA）认可的实验室中进行序列变异检测的临床和技术验证，并由具有委员会认证的临床分子遗传学家或同等人员进行解读。
