Collaborator: ClinVar
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Scaling resolution of variant classification differences in ClinVar between 41 clinical laboratories through an outlier approach
Abstract ClinVar provides open access to variant classifications shared from many clinical laboratories. Although most classifications are consistent across laboratories, classification differences exist. To facilitate resolution of classification differences on a large scale, clinical laboratories were encouraged to reassess outlier classifications of variants with medically significant differences (MSDs). Outliers were identified by first comparing ClinVar…
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Recommendations for interpreting the loss of function PVS1 ACMG/AMP variant criterion
Abstract The 2015 ACMG/AMP sequence variant interpretation guideline provided a framework for classifying variants based on several benign and pathogenic evidence criteria, including a pathogenic criterion (PVS1) for predicted loss of function variants. However, the guideline did not elaborate on specific considerations for the different types of loss of function variants, nor did it provide…
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Scaling the Resolution of Sequence Variant Classification Discrepancies in ClinVar
The first phase of this project involved ClinVar submissions from 41 clinical laboratories, and found that 84.6% of classifications were concordant and only 2.7% (650 variants) of variants were medically significant differences (MSDs) with potential to impact medical management. Of the discrepant results that have been reviewed, 62.3% have now been resolved through data sharing…
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A survey of current practices for genomic sequencing test interpretation and reporting processes in US laboratories
Abstract Purpose While the diagnostic success of genomic sequencing expands, the complexity of this testing should not be overlooked. Numerous laboratory processes are required to support the identification, interpretation, and reporting of clinically significant variants. This study aimed to examine the workflow and reporting procedures among US laboratories to highlight shared practices and identify areas…
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Clinical laboratories collaborate to resolve differences in variant interpretations submitted to ClinVar
Abstract Purpose Data sharing through ClinVar offers a unique opportunity to identify interpretation differences between laboratories. As part of a ClinGen initiative, four clinical laboratories (Ambry, GeneDx, Partners Healthcare Laboratory for Molecular Medicine, and University of Chicago Genetic Services Laboratory) collaborated to identify the basis of interpretation differences and to investigate if data sharing and…
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ClinGen and Genetic Testing
Abstract On autopsy, a patient is found to have hypertrophic cardiomyopathy. The patient’s family pursues genetic testing that shows a “likely pathogenic” variant for the condition on the basis of a study in an original research publication. Given the dominant inheritance of the condition and the risk of sudden cardiac death, other family members are…
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Clinical laboratories implement the ACMG/AMP guidelines to resolve differences in variant interpretations submitted to ClinVar.
Ranked as a top poster* In 2015, the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) published a joint guideline for variant interpretation that provides a framework to classify variants. As part of a ClinGen initiative, four clinical laboratories, Ambry Genetics, GeneDx, Partners Laboratory for Molecular Medicine…
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Performance of ACMG/AMP variant interpretation guidelines among nine laboratories in the Clinical Sequencing Exploratory Research consortium
Performance of ACMG/AMP variant interpretation guidelines among nine laboratories in the Clinical Sequencing Exploratory Research consortium