ACMG previously developed recommendations for standards for interpretation of sequence variations. We now present the updated revised recommendations. Here, we describe six interpretative categories of sequence variations: (1) sequence variation is previously reported and is a recognized cause of the disorder; (2) sequence variation is previously unreported and is of the type which is expected to cause the disorder; (3) sequence variation is previously unreported and is of the type which may or may not be causative of the disorder; (4) sequence variation is previously unreported and is probably not causative of disease; (5) sequence variation is previously reported and is a recognized neutral variant; and (6) sequence variation is previously not known or expected to be causative of disease, but is found to be associated with a clinical presentation. We emphasize the importance of appropriate reporting of sequence variations using standardized terminology and established databases, and of clearly reporting the limitations of sequence-based testing. We discuss follow-up studies that may be used to ascertain the clinical significance of sequence variations, including the use of additional tools (such as predictive software programs) that may be useful in variant classification. As more information becomes available allowing the interpretation of a new sequence variant, it is recommended that the laboratory amend previous reports and provide updated results to the physician. The ACMG strongly recommends that the clinical and technical validation of sequence variation detection be performed in a CLIA-approved laboratory and interpreted by a board-certified clinical molecular geneticist or equivalent. Genet Med 2008:10(4):294-300.These recommendations for the standardization of interpretation and reporting of sequence variations identified in the course of providing clinical laboratory services are intended (1) to provide a framework for laboratories for the interpretation and reporting of such test results, and (2) to aid referring clinicians by educating them as to possible testing outcomes so that they may inform their patients and families appropriately. These revised recommendations are based on the foundation laid by the previous ACMG practice guideline recommendations in 2000. 1
I. INTERPRETATIVE CATEGORIES AND DEFINITIONS OF SEQUENCE VARIATIONSIncreasingly, clinical molecular laboratories are detecting novel sequence variations in the course of testing patient spec-
Specific features of personal and family history can be used to assess the likelihood of identifying a mutation in BRCA1 or BRCA2 in individuals tested in a clinical setting.
Specific features of personal and family history can be used to assess the likelihood of identifying a mutation in BRCA1 or BRCA2 in individuals tested in a clinical setting.
Personal and family history characteristics can accurately predict the outcome of genetic testing in a large population at risk of Lynch syndrome. The PREMM(1,2) model provides clinicians with an objective, easy-to-use tool to estimate the likelihood of finding mutations in the MLH1/MSH2 genes and may guide the strategy for molecular evaluation.
It appears that early IBTR is a significant predictor for distant metastases. Whether early breast tumor relapse is a marker for or cause of distant metastases remains a controversial and unresolved issue. Implications for adjuvant systemic therapy at the time of breast relapse are discussed.
A tactical approach: C3‐chiral ancillary ligands such as tris(oxazolinyl)ethane allow stereocontrol in olefin polymerization (see scheme). An alkyl ScIII catalyst polymerizes 1‐hexene with activities ranging from 2000 to 36 000 kg mol−1 h−1 (at −30 to +21 °C) and good tacticity control at low temperatures.
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