Skip to content Skip to footer

Use cases: Rare diseases

The Rare Disease Use Case has been the central use case demonstrating the 1+MG Infrastructure to date. The outcomes expected from the 1+MG initiative for this use case include:

  • Improved knowledge of the genetic make-up of RDs
  • Anticipation of diagnosis and solving the unsolved
  • Better understanding of the phenotypic variability and longitudinal course of RD
  • Support clinicians to make decisions on how to adapt treatment and care pathways

The scenario that was demonstrated was of a rare disease researcher who was investigating congenital myasthenic syndromes. A child patient was suspected of having a monogenic mutation which caused the clinical features observed in the child, including neonatal hypotonia and distal arthrogryposis, as well as an inability to walk and lower respiratory tract infections.

As the mutation was suspected to be monogenic, the child and parents all had their genomes sequenced and the associated bioinformatic analysis was performed which discovered a de-novo mutation in the RYR1 gene within the child.

Given this information, the researcher wanted to know:

  1. Are there any other individuals with the same mutation or allelic variant?
  2. If there are, what is their diagnosis i.e. phenotype? What can be derived from them for the prognosis?
  3. What is the variant frequency across populations?
  4. Is there an association between the gene mutation and the disease?

Rare disease Proof of Concept


Rare disease proof of concept

Proof of Concept completed for Rare Disease utilising a number of existing GA4GH Standards

  • Beacon
  • DUO
  • VCF
  • Crypt4gh
  • Htsget
  • Phenopackets
  • Passports
  • TES & WES
  • And other existing services (Matchmaker Exchange, FEGA & Life Science AAI).

Catalogue of Met and Unmet Use Case Needs


  • Planned further activities to meet the needs of the use cases as of 13/12/2022

  • Met and unmet use cases will be recorded in Zenhub

  • EJP RD Rare Disease Patient Registries Initiative:

  • EJP RD Rare Disease Patient Registries Initiative:

Rare disease survey (in progress)


It covers different aspects related to sequencing data generation/capacities, data availability for rare disease patients and info on diagnostic yield, analytical pipelines, and availability on associated clinical info. This has been sent to B1MG working group 8 experts and major rare disease sequencing centers in each member state.

We are still working on the content for this page. If you are interested in adding to the page, then:

Feel free to contribute

This is a community-driven website, so contributions are welcome! You will, of course, be listed as a contributor on the page.