Performance of interpreting the variants of long QT syndrome according ACMG guidelines by four clinical gene screening agencies from Beijing
10.3760/cma.j.issn.0253-3758.2018.11.008
- VernacularTitle: 北京地区应用ACMG指南在长QT综合征变异分析中的一致性评估
- Author:
Nian LIU
1
;
Linling LI
;
Yanfei RUAN
;
Qianqian ZHAO
;
Mengxia ZHANG
;
Xin LI
;
Songnan WEN
;
Rong BAI
;
Jianzeng DONG
;
Changsheng MA
Author Information
1. Cardiology Center of Beijing Anzhen Hospital, Capital Medical University, National Clinical Research Center for Cardiovascular Diseases & Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing 100029, China
- Publication Type:Journal Article
- Keywords:
Genetic variation;
Long QT syndrome;
Pathogenic classification
- From:
Chinese Journal of Cardiology
2018;46(11):857-861
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To analyze the interpretation results on the pathogenic classification of KCNH2 variants and SCN5A variants of long QT syndrome (LQTS) based on American College of Medical Genetics and Genomics (ACMG) guidelines by 4 clinical gene screening agencies from Beijing.
Methods:Pathogenic classification of 16 variants in KCNH2 and SCN5A was made by 4 clinical gene screening agencies from Beijing based on ACMG guideline. Krippendorff's alpha was used to assess the inter-agency variation consistency.
Results:All 4 agencies made pathogenic assessment on all the variants and provided the interpretation results for the classification. For the eight variants from the patients with LQTS, the consistency of classification was only 1/8 and the alpha test value was - 0.01. For the eight variables from incidental findings, the consistency of classification was 4/8 and the alpha test value was 0.407. Evidence analysis of the 4 variants with large differences in classification among agencies showed that the main reasons for the discrepancies originated from the comprehensiveness of the literature search and the inconsistency of the subjective determination of the evidence grade.
Conclusion:The consistency of the pathogenic classification of LQTS gene variants based on ACMG guidelines among clinical gene screening agencies from Beijing is poor, which will result in great impact on the clinical treatment strategies of the patients with LQTS. The standardization of pathogenic evaluation of variants in clinical gene screening agencies needs to be improved urgently.
