Reasons and Resolutions for Inconsistent Variant Interpretation

被引：3

作者：

Lin, Liling ^{[1
,2
]}

Pan, Hong ^{[2
]}

Qi, Yu ^{[2
]}

Ma, Yinan ^{[2
]}

Qiu, Ling ^{[1
,3
,4
]}

机构：

[1] Peking Union Med Coll Hosp, Dept Lab Med, 1 Shuaifu Yuan, Beijing 100730, Peoples R China

[2] Peking Univ First Hosp, Dept Cent Lab, 8 Xishiku St, Beijing 100034, Peoples R China

[3] Peking Union Med Coll, Peking Union Med Coll Hosp, State Key Lab Complex Severe & Rare Dis, Beijing 100730, Peoples R China

[4] Chinese Acad Med Sci, Beijing 100730, Peoples R China

来源：

HUMAN MUTATION | 2023年 / 2023卷

关键词：

INTERPRETATION GUIDELINES; PATHOGENICITY CLASSIFICATION; CLINICAL INTERPRETATION; GENETIC DIAGNOSIS; SEQUENCE VARIANTS; MEDICAL GENETICS; AMERICAN-COLLEGE; LABORATORIES; CLINGEN; RECOMMENDATIONS;

D O I：

10.1155/2023/4955235

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

In the postgenomic era, variant interpretation is crucial for diagnosing monogenic diseases, which is the premise of precision medicine. The bottleneck and difficulty of genetic disease diagnosis have switched from the inaccessibility of detection technology to the interpretation of sequencing results. Multiple studies have suggested that the inconsistency rate of interlaboratory variant interpretation is approximately 10 similar to 40%. However, many clinicians have not paid enough attention to this area at present. In this review, we summarized the reasons for inconsistency, including classification methodology, information obtained by the interpreter, evidence application, and expert judgement. For clinicians, genetic counsellors, and molecular pathologists, it is necessary to reevaluate genetic reports, especially those supported by old literature and databases in clinical practice. For unresolvable cases, pedigree analysis, collaboration with research labs for functional experiments, and long-term follow-up to combine advanced clinical presentations with updated data and literature are needed.

引用

页数：11

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