Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Genome sequencing identifies monogenic causes in adults with metabolic diseases.

Journal of the Endocrine Society·2026
Same author

Exome sequencing early in outpatient evaluation in NCGENES 2: Changing the course of the diagnostic odyssey?

HGG advances·2026
Same author

Direct-to-Consumer Genetic Testing.

NEJM evidence·2025
Same author

Primary Care Provider Perspectives on Expanded Genomic Screening in Children.

Research square·2025
Same author

When families bridge the research-clinical divide: An exploration of values regarding cascade screening in genomic research.

Genetics in medicine open·2025
Same author

Age-Based Genomic Screening: Pediatric Providers' Perspectives on Implementation.

Public health genomics·2025

Related Experiment Video

Updated: Dec 3, 2025

Identification and Classification of Position-specific GABAA Receptor Subunit Missense Variants for Their Role In Hippocampal Pyramidal Neurons
08:04

Identification and Classification of Position-specific GABAA Receptor Subunit Missense Variants for Their Role In Hippocampal Pyramidal Neurons

Published on: June 6, 2025

911

Variant Classification Concordance using the ACMG-AMP Variant Interpretation Guidelines across Nine Genomic

Laura M Amendola1, Kathleen Muenzen2, Leslie G Biesecker3

  • 1Department of Medicine, Division of Medical Genetics, University of Washington Medical Center, Seattle, WA 98195, USA.

American Journal of Human Genetics
|October 27, 2020
PubMed
Summary

Harmonizing variant classification across clinical genomics laboratories is crucial. This study found 54% concordance, with discordance affecting clinical recommendations in 11%, highlighting the need for shared evidence and guidance.

Keywords:
ACMG-AMP recommendationsgenomic implementationgermline variant classification

More Related Videos

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
09:34

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

Published on: April 4, 2018

34.4K
Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
07:15

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation

Published on: January 16, 2019

11.2K

Related Experiment Videos

Last Updated: Dec 3, 2025

Identification and Classification of Position-specific GABAA Receptor Subunit Missense Variants for Their Role In Hippocampal Pyramidal Neurons
08:04

Identification and Classification of Position-specific GABAA Receptor Subunit Missense Variants for Their Role In Hippocampal Pyramidal Neurons

Published on: June 6, 2025

911
Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
09:34

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

Published on: April 4, 2018

34.4K
Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
07:15

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation

Published on: January 16, 2019

11.2K

Area of Science:

  • Genomics
  • Clinical Genetics
  • Bioinformatics

Background:

  • Harmonizing variant pathogenicity classification is essential for advancing clinical genomics.
  • Discordance in variant classification can impact patient care and genetic testing interpretation.

Purpose of the Study:

  • To explore current sources of discordance in variant pathogenicity classification across multiple laboratories.
  • To assess the level of concordance in variant classification using standardized guidelines.

Main Methods:

  • Eight CLIA-accredited laboratories submitted 158 classified variants in ACMG secondary finding genes.
  • Variants were independently re-annotated and classified by two additional laboratories using ACMG-AMP guidelines.
  • Discordant variants underwent teleconference and email review for further assessment.

Main Results:

  • Overall five-category concordance was achieved for 54% of variants.
  • Eleven percent of variants showed discordance that could alter clinical recommendations (Pathogenic/Likely Pathogenic vs. VUS/Likely Benign/Benign).
  • Post-review concordance reached 84% for initially discordant variants.

Conclusions:

  • This study provides an updated estimate of variant concordance in clinical genomics.
  • Identified discordance highlights the need for improved sharing of variant classifications and evidence.
  • Ongoing efforts by ClinGen and inter-laboratory collaboration are vital for increasing concordance and standardizing clinical genomics practices.