Collaborator: Harvard University
-
Prevalence of germline variants in inflammatory breast cancer
Abstract Background Inflammatory breast cancer (IBC) is an uncommon and aggressive subtype of breast cancer associated with early disease recurrence and short survival. The prevalence of germline variants in cancer predisposition genes has not been systematically evaluated in women with IBC. Methods Among 301 women enrolled in the clinical IBC registry at a single institution…
-
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…
-
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…
-
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…