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

Genome-wide Association Studies-GWAS01:11

Genome-wide Association Studies-GWAS

13.6K
Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
13.6K
Comparing Copy Number Variations and SNPs02:26

Comparing Copy Number Variations and SNPs

17.8K
Sequencing of the human genome has opened up several best-kept secrets of the genome. Scientists have identified thousands of genome variations that exist within a population. These variations can be a single nucleotide or a larger chromosomal variation.
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
17.8K
Single Nucleotide Polymorphisms-SNPs01:05

Single Nucleotide Polymorphisms-SNPs

15.3K
A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
15.3K
Cardiomyopathy I: Introduction and Classification01:25

Cardiomyopathy I: Introduction and Classification

19
Cardiomyopathy, or CMP, is a group of diseases affecting the myocardial structure, impairing its ability to pump blood effectively. This condition can lead to arrhythmias, heart failure, or sudden cardiac death.Cardiomyopathies are classified into primary and secondary categories:Primary Cardiomyopathy refers to conditions involving only the heart muscle that are often idiopathic (of unknown cause) or genetic. They primarily affect the myocardium without the involvement of other systemic...
19

You might also read

Related Articles

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

Sort by
Same author

Spectroscopic correlation tomography (SpCT) for visualization of spatial correlations in volumetric OCT scans.

Biomedical optics express·2026
Same author

The Cardiac Sarcomere: From development of heritable cardiomyopathies to gene and precision therapies.

Journal of cardiovascular pharmacology·2026
Same author

Author Correction: Ventricular assist device unloading reverses microvascular senescence in single ventricle disease.

Nature cardiovascular research·2026
Same author

Perm1 Gene Therapy Mitigates PRDM16-Associated Cardiomyopathy.

bioRxiv : the preprint server for biology·2026
Same author

Scalable System-Wide CYP2C19 Pharmacogenomic Testing Reveals 38% Excess Incidence of Adverse Events in Metabolizers Receiving Inappropriate Prescriptions.

Circulation. Genomic and precision medicine·2026
Same author

A Hypoxia-reoxygenation Injury Model in Self-assembling Human Cardioids.

Journal of visualized experiments : JoVE·2026

Related Experiment Video

Updated: Jul 24, 2025

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

11.0K

DiscoVari: A Web-Based Precision Medicine Tool for Predicting Variant Pathogenicity in Cardiomyopathy- and

Leonie M Kurzlechner1, Sujata Kishnani1, Shawon Chowdhury1

  • 1Department of Pediatrics, Division of Pediatric Cardiology (LMK, SK, SC, SLA, MEM-M, LEP, MBR, LAP, APL), Duke University School of Medicine, Durham, NC.

Circulation. Genomic and Precision Medicine
|July 6, 2023
PubMed
Summary

Advancements in genetic testing increase incidentally found cardiac disease variants. A new tool, DiscoVari, uses signal-to-noise analysis to identify pathogenic hotspots, improving variant interpretation for sudden cardiac death risk.

Keywords:
channelopathyexome sequencinglong QT syndromeprobabilitysyncope

More Related Videos

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
00:06

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila

Published on: August 20, 2019

13.7K
Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information
09:37

Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information

Published on: August 15, 2019

9.8K

Related Experiment Videos

Last Updated: Jul 24, 2025

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

11.0K
In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
00:06

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila

Published on: August 20, 2019

13.7K
Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information
09:37

Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information

Published on: August 15, 2019

9.8K

Area of Science:

  • Genetics and Genomics
  • Cardiovascular Medicine
  • Bioinformatics

Background:

  • Genetic testing increasingly identifies incidental cardiac disease-associated gene variants.
  • These variants can pose a risk for sudden cardiac death, necessitating accurate diagnostic interpretation.
  • There is a growing need for tools to evaluate the pathogenicity of these variants.

Purpose of the Study:

  • To identify pathogenic hotspots in genes associated with sudden cardiac death.
  • To develop a web-based precision medicine tool, DiscoVari, for improved variant evaluation.
  • To leverage amino acid-level signal-to-noise (S:N) analysis for variant interpretation.

Main Methods:

  • Calculated amino acid-level S:N ratios by normalizing minor allele frequencies of pathogenic variants to healthy populations.
  • Defined pathogenic hotspots as amino acids exceeding a gene-specific S:N threshold.
  • Developed DiscoVari using JavaScript, ReactJS, Next.js, and NodeJS; validated with ClinVar and clinical cohort data.

Main Results:

  • DiscoVari identified a higher proportion of likely pathogenic/pathogenic variants in hotspots (43.1%) compared to benign variants (17.8%).
  • A significant majority of variants reclassified to pathogenic (75.3%) and clinical pathogenic variants (73.1%) were located within identified hotspots.
  • No likely benign/benign variants from the clinical cohort were found in hotspots, indicating high specificity.

Conclusions:

  • DiscoVari effectively identifies disease-susceptible amino acid residues using amino acid-specific S:N ratios.
  • The tool aids in the reliable evaluation of genetic variants associated with cardiac diseases.
  • DiscoVari represents a valuable resource for precision medicine in cardiology.