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Updated: Feb 16, 2026

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
Published on: January 16, 2019
Clinical implications and considerations for evaluation of in silico algorithms for use with ACMG/AMP clinical
Lora J H Bean1,2, Madhuri R Hegde3,4,5
1Department of Human Genetics, Emory University, Atlanta, GA, USA. lorabean@eglgenetics.com.
Abstract:
Clinical genetics laboratories have recently adopted guidelines for the interpretation of sequence variants set by the American College of Medical Genetics (ACMG) and Association for Molecular Pathology (AMP). The use of in silico algorithms to predict whether amino acid substitutions result in human disease is inconsistent across clinical laboratories. The clinical genetics community must carefully consider how in silico predictions can be incorporated into variant interpretation in clinical practice.Please see related Research article: https://doi.org/10.1186/s13059-017-1353-5.

