Communicating new knowledge on previously reported genetic variants

Abstract

Genetic tests often identify variants whose significance cannot be determined at the time they are reported. In many situations, it is critical that clinicians be informed when new information emerges on these variants. It is already extremely challenging for laboratories to provide these updates. These challenges will grow rapidly as an increasing number of clinical genetic tests are ordered and as the amount of patient DNA assayed per test expands; the challenges will need to be addressed before whole-genome sequencing is used on a widespread basis.Information technology infrastructure can be useful in this context. We have deployed an infrastructure enabling clinicians to receive knowledge updates when a laboratory changes the classification of a variant. We have gathered statistics from this deployment regarding the frequency of both variant classification changes and the effects of these classification changes on patients. We report on the system's functionality as well as the statistics derived from its use.Genet Med advance online publication 5 April 2012.

Figure 1

Variant classification changes—HCM data. Geneticist-approved variant classification changes that have occurred since 2004 on variants in 11 genes on the HCM CardioChip Test. Only changes that would have affected at least one preexisting patient report were counted. The figure also reflects only classification changes relative to HCM and does not reflect data from other diseases. These 214 changes occurred over ~7 years within our knowledge base of 1,472 HCM variants. Over this period, 4,923 tests were conducted, including 2,644 probands and 2,279 family members. HCM, hypertrophic cardiomyopathy.

Figure 2

GeneInsight workflow. This figure depicts the high-level workflow enabled by GeneInsight. The solid black arrows represent the core reporting workflow that occurs each time a test is ordered and a sample received. The dashed arrows show an entirely automated ancillary workflow that occurs when the category of a variant is changed. This typically occurs in the course of reporting a test but can also occur independent of a test order. As a high-level view, this figure does not represent all system-level communication that occurs during the reporting process.

Figure 3

The GeneInsight Clinic interface. This interface image provides an example of how a screen can be assembled to manage clinical genetic test results. Users can navigate to this screen either by searching for a patient or by clicking patient-specific links in alert e-mails. (These e-mails contain no protected health information.) From this screen, users can pull up the report associated with each case or obtain additional information when clicking on a specific variant. They can also see whether the laboratory has reclassified a variant since the test was originally reported. Boxes have been added for emphasis and do not appear on the actual screen. (Adapted from ref. .)