Exploring concordance and discordance for return of incidental findings from clinical sequencing.
Exploring concordance and discordance for return of incidental findings from clinical sequencing.
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DOI：
10.1038/gim.2012.21
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发表时间：
2012-04
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
探索特定的条件和遗传变异的类型，在遗传学专家建议应返回作为偶然发现在临床测序。16位临床遗传学和/或分子医学专家选择了99种常见疾病的变异，如果在全基因组测序中偶然发现，则返回给订购医生。对于大多数情况，专家们独立考虑了成人和未成年儿童的3种分子情景：已知的致病性突变，假定致病性的截短变异（已知其他截短变异是致病性的），或计算机预测的致病性错义变异。平均而言，对于成人和儿童，每个专家分别在已知的99个致病突变类别中选择83.5个和79.0个条件或基因，在72个截断变异类别中选择57.0个和53.5个，在72个错义变异类别中选择33.4个和29.7个。在成人/已知致病突变类别中，21种情况或基因的一致性为100%，64种情况或基因的一致性为80%或更高。如果在全外显子组或全基因组测序过程中偶然发现64种情况或基因，专家们对结果的回报高度一致。
To explore specific conditions and types of genetic variants that specialists in genetics recommend should be returned as incidental findings in clinical sequencing. Sixteen specialists in clinical genetics and/or molecular medicine selected variants in 99 common conditions to return to the ordering physician if discovered incidentally through whole genome sequencing. For most conditions, the specialists independently considered 3 molecular scenarios for both adults and minor children: a known pathogenic mutation, a truncating variant presumed pathogenic (where other truncating variants were known to be pathogenic), or a missense variant predicted in silico to be pathogenic. On average, for adults and children respectively, each specialist selected 83.5 and 79.0 conditions or genes out of 99 in the known pathogenic mutation categories, 57.0 and 53.5 out of 72 in the truncating variant categories, and 33.4 and 29.7 out of 72 in the missense variant categories. Concordance in favor of disclosure within the adult/known pathogenic mutation category was 100% for 21 conditions or genes and 80% or higher for 64 conditions or genes. Specialists were highly concordant for the return of findings in 64 conditions or genes if discovered incidentally during whole exome or whole genome sequencing.
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影响因子：
8.8
作者：
Worthey, Elizabeth A.;Mayer, Alan N.;Dimmock, David P.
通讯作者：
Dimmock, David P.
DOI：
10.1097/gim.0b013e318203cff2
发表时间：
2011-03
期刊：
Genetics in medicine : official journal of the American College of Medical Genetics
影响因子：
--
作者：
Berg JS;Evans JP;Leigh MW;Omran H;Bizon C;Mane K;Knowles MR;Weck KE;Zariwala MA
通讯作者：
Zariwala MA
DOI：
10.1056/nejmoa0908094
发表时间：
2010-04-01
期刊：
The New England journal of medicine
影响因子：
--
作者：
Lupski JR;Reid JG;Gonzaga-Jauregui C;Rio Deiros D;Chen DC;Nazareth L;Bainbridge M;Dinh H;Jing C;Wheeler DA;McGuire AL;Zhang F;Stankiewicz P;Halperin JJ;Yang C;Gehman C;Guo D;Irikat RK;Tom W;Fantin NJ;Muzny DM;Gibbs RA
通讯作者：
Gibbs RA
影响因子：
120.7
作者：
Link, Daniel C.;Schuettpelz, Laura G.;Shen, Dong;Wang, Jinling;Walter, Matthew J.;Kulkarni, Shashikant;Payton, Jacqueline E.;Ivanovich, Jennifer;Goodfellow, Paul J.;Le Beau, Michelle;Koboldt, Daniel C.;Dooling, David J.;Fulton, Robert S.;Bender, R. Hugh F.;Fulton, Lucinda L.;Delehaunty, Kimberly D.;Fronick, Catrina C.;Appelbaum, Elizabeth L.;Schmidt, Heather;Abbott, Rachel;O'Laughlin, Michelle;Chen, Ken;McLellan, Michael D.;Varghese, Nobish;Nagarajan, Rakesh;Heath, Sharon;Graubert, Timothy A.;Ding, Li;Ley, Timothy J.;Zambetti, Gerard P.;Wilson, Richard K.;Mardis, Elaine R.
通讯作者：
Mardis, Elaine R.
影响因子：
64.8
作者：
Green, Eric D.;Guyer, Mark S.
通讯作者：
Guyer, Mark S.