Reassessment of Genomic Sequence Variation to Harmonize Interpretation for Personalized Medicine

被引：47

作者：

Garber, Kathryn B. ^{[1
,2
]}

Vincent, Lisa M. ^{[3
]}

Alexander, John J. ^{[1
,2
]}

Bean, Lora J. H. ^{[1
,2
]}

Bale, Sherri ^{[3
]}

Hegde, Madhuri ^{[1
,2
]}

机构：

[1] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA 30322 USA

[2] Emory Genet Lab, Decatur, GA 30033 USA

[3] GeneDx, Gaithersburg, MD 20877 USA

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2016年 / 99卷 / 05期

关键词：

VARIANT-INTERPRETATION; MUTATIONS; GENE; CARDIOMYOPATHY; CLASSIFICATION; LABORATORIES; GUIDELINES; PHENOTYPE; NONSENSE;

D O I：

10.1016/j.ajhg.2016.09.015

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Accurate interpretation of DNA sequence variation is a prerequisite for implementing personalized medicine. Discrepancies in interpretation between testing laboratories impede the effective use of genetic test results in clinical medicine. To better understand the underpinnings of these discrepancies, we quantified differences in variant classification internally over time and those between our diagnostic laboratory and other laboratories and resources. We assessed the factors that contribute to these discrepancies and those that facilitate their resolution. Our process resolved 72% of nearly 300 discrepancies between pairs of laboratories to within a one-step classification difference and identified key sources of data that facilitate changes in variant interpretation. The identification and harmonization of variant discrepancies will maximize the clinical use of genetic information; these processes will be fostered by the accumulation of additional population data as well as the sharing of data between diagnostic laboratories.

引用

页码：1140 / 1149

页数：10

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