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Intro
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ACMG Guidelines General variant classification guideline
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Structural Data Number of structures available
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Available Lines of Evidence What can we use to assess variants?
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Protein Structure Defines the Function What is the central dogma of molecular biology?
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Information Levels DNA, RNA, and protein
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Amino Acids The basic building blocks
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Sequence Alignments & Conservation Additional data for variant assessment
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Protein Structure Four levels of protein structure
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Structural Biology & 3D Protein Structure Accounting for folding
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Biophysical Method Overview Using classical mechanics to represent proteins
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Molecular Interactions Functional disruption through lost interactions
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Structural Biology in Variant Assessment Possible outcomes
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Predicted Stability Changes Comparing energies
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Structural Motif Disruption Structural details of motif assessment
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Biomolecular Interactions Arginine finger interacts with the DNA
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BRCA2 p.D2723N Destabilizing structure
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Structural Biology Applications Tools in the toolbox Dynamics
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Acknowledgements Thank you for your contributions, insight, and help
Description:
Explore the application of structural biology in genetic variant assessment through this informative webinar presented by Ambry Genetics. Gain insights into leveraging biophysical principles to evaluate the functional impact of genetic variants, complementing traditional assessment methods. Learn about general biophysical approaches and their practical applications in determining variant deleteriousness. Discover how structural evidence can be combined with other categories of evidence to reassess variants of unknown significance. Delve into topics such as ACMG guidelines, protein structure and function, amino acids, sequence alignments, conservation, and molecular interactions. Understand the four levels of protein structure and how they relate to variant assessment. Examine case studies, including the analysis of BRCA2 p.D2723N, to see structural biology principles in action. Benefit from the expertise of Dr. Adam Chamberlin, Principal Structural Biologist at Ambry Genetics, as he shares his extensive knowledge in quantum and physical chemistry, structural biology, and mathematical modeling. Read more

Using Structural Biology to Support Variant Assessment - Webinar - Ambry Genetics

Ambry Genetics
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