Collaborator: Albert Einstein College of Medicine
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Exploration of germline mutation burden in a hereditary cancer panel cohort identifies gaps in cancer risk associations and testing and management guidelines.
In a large multigene panel testing cohort, genes commonly mutated among patients with breast, colorectal, ovarian, and endometrial cancers generally have established cancer risk estimates and management recommendations for the respective cancer types. In contrast, genes commonly mutated among pancreatic and prostate cancer patients are lacking associated cancer risk and management data. Research efforts focused…
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Combined genetic and splicing analysis of BRCA1 c.[594-2A>C; 641A>G] highlights the relevance of naturally occurring in-frame transcripts for developing disease gene variant classification algorithms.
Abstract A recent analysis using family history weighting and co-observation classification modeling indicated that BRCA1 c.594-2A > C (IVS9-2A > C), previously described to cause exon 10 skipping (a truncating alteration), displays characteristics inconsistent with those of a high risk pathogenic BRCA1 variant. We used large-scale genetic and clinical resources from the ENIGMA, CIMBA 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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Cancer risks associated with predisposition gene mutations identified by hereditary cancer panel testing of 85,000 patients
Abstract Clinical genetic testing of individuals with a personal or family history of breast and ovarian cancer using panels for BRCA1/2 and other candidate cancer predisposition genes have become routine clinical practice. While the cumulative lifetime and age specific risks associated with mutations in BRCA1/2 in high-risk families and in the general population are well…
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Breast cancer risks associated with mutations in cancer predisposition genes identified by clinical genetic testing of 50,000 breast cancer patients
Clinical genetic testing panels are broadly used to gather information about cancer predisposition in individuals with personal and/or family history of breast cancer. However, the involvement of several of the genes that are included on clinical testing panels in predisposition to breast cancer has recently come into question. In addition, accurate risk estimates for breast…
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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…