An Educational Assessment of Evidence Used for Variant Classification: A Report of the Association for Molecular Pathology.

Autor:	Lyon E; The Variant Interpretation Testing Among Laboratories (VITAL) Working Group of the Clinical Practice Committee, Association for Molecular Pathology (AMP), Rockville, Maryland; HudsonAlpha Institute for Biotechnology, Huntsville, Alabama., Temple-Smolkin RL; Association for Molecular Pathology (AMP), Rockville, Maryland., Hegde M; The Variant Interpretation Testing Among Laboratories (VITAL) Working Group of the Clinical Practice Committee, Association for Molecular Pathology (AMP), Rockville, Maryland; Global Genetics Laboratory, PerkinElmer Genomics, Pittsburgh, Pennsylvania., Gastier-Foster JM; The Variant Interpretation Testing Among Laboratories (VITAL) Working Group of the Clinical Practice Committee, Association for Molecular Pathology (AMP), Rockville, Maryland; Departments of Pediatrics and Pathology/Immunology, Baylor College of Medicine, Houston, Texas; Pathology Department, Texas Children's Hospital, Houston, Texas; Department of Pathology, The Ohio State University College of Medicine, Columbus, Ohio., Palomaki GE; The Variant Interpretation Testing Among Laboratories (VITAL) Working Group of the Clinical Practice Committee, Association for Molecular Pathology (AMP), Rockville, Maryland; Department of Pathology and Laboratory Medicine, Women & Infants Hospital and the Alpert Medical School at Brown University, Providence, Rhode Island., Richards CS; The Variant Interpretation Testing Among Laboratories (VITAL) Working Group of the Clinical Practice Committee, Association for Molecular Pathology (AMP), Rockville, Maryland; Department of Molecular and Medical Genetics and Knight Diagnostic Laboratories, Oregon Health & Science University, Portland, Oregon. Electronic address: richarsu@ohsu.edu.
Jazyk:	angličtina
Zdroj:	The Journal of molecular diagnostics : JMD [J Mol Diagn] 2022 Jun; Vol. 24 (6), pp. 555-565. Date of Electronic Publication: 2022 Apr 13.
DOI:	10.1016/j.jmoldx.2021.12.014
Abstrakt:	The Association for Molecular Pathology Variant Interpretation Testing Among Laboratories (VITAL) Working Group convened to evaluate the Standards and Guidelines for the Interpretation of Sequence Variants implementation into clinical practice, identify problematic classification rules, and define implementation challenges. Variants and associated clinical information were provided to volunteer respondents. Participant variant classifications were compared with intended consensus-derived classifications of the Working Group. The 24 variant challenges received 1379 responses; 1119 agreed with the intended response (81%; 95% CI, 79% to 83%). Agreement ranged from 44% to 100%, with 16 challenges (67%; 47% to 82%) reaching consensus (≥80% agreement). Participant classifications were also compared to a calculated interpretation of the ACMG Guidelines using the participant-reported criteria as input. The 24 variant challenges had 1368 responses with specific evidence provided and 1121 (82%; 80% to 84%) agreed with the calculated interpretation. Agreement for challenges ranged from 63% to 98%; 15 (63%; 43% to 79%) reaching consensus. Among 81 individual participants, 32 (40%; 30% to 50%) reached agreement with at least 80% of the intended classifications and 42 (52%; 41% to 62%) with the calculated classifications. This study demonstrated that although variant classification remains challenging, published guidelines are being utilized and adapted to improve variant calling consensus. This study identified situations where clarifications are warranted and provides a model for competency assessment. (Copyright © 2022 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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