Applications close: Monday March 27th, 2023
For many disease genes there are significant numbers of potentially disease-causing variants which do not reach the current threshold for definitive genetic diagnosis. This can be burdensome for variant interpretation and clinical reporting, particularly for rare disease.
To address this:
The AFGN invites expressions of interest to develop gene-specific functional genomics platforms to resolve multiple VUS in priority genes for Australian diagnostic labs and clinicians
(link to register below).
The following list represents the rare disease genes with the highest number of VUS reported in Shariant, a cloud-based sharing platform that captures clinically curated variants from accredited labs and clinical services across Australia.
| Gene | Disease association | Inheritance pattern | # of VUS in Shariant | # of VUS in ClinVar |
|---|---|---|---|---|
| RYR1 RYR1 ryanodine receptor 1 |
Neuromuscular disease | Autosomal Dominant, Autosomal recessive |
36 (53%) |
2118 (42%) |
| PKD1 Polycystin 1 |
Kidney disease | Autosomal Dominant | 57 (41%) |
794 (33%) |
| MYH7 Myosin heavy chain 7 |
Cardiomyopathy & Myopathy | Autosomal Dominant | 34 (42%) |
1740 (50%) |
| MYBPC3 Myosin binding protein C3 |
Cardiomyopathy | Autosomal Dominant, Autosomal recessive |
28 (30%) |
1136 (40%) |
| TTN Titin |
Cardiomyopathy & Myopathy | Autosomal Dominant, Autosomal recessive |
49 (53%) |
7837 (37%) |
| ABCA4 ATP binding cassette subfamily A member 4 |
Retinal degeneration | Autosomal recessive | 29 (31%) |
815 (30%) |
| FLNC Filamin C |
Cardiomyopathy & Myopathy | Autosomal Dominant | 38 (86%) |
1587 (50%) |
| USH2A Usherin |
Usher syndrome | Autosomal recessive | 40 (38%) |
1696 (31%) |
| RP1L1 RP1-like protein 1 |
Retinal degeneration | Autosomal Dominant, Autosomal recessive |
24 (86%) |
313 (37%) |
| ADGRV1 Adhesion G protein-coupled receptor V1 |
Usher syndrome | Autosomal Dominant, Autosomal recessive |
30 (67%) |
1665 (48%) |
*Presented in order of highest to lowest priority as determined by our clinical and scientific review committees
Register your interest to receive a project proposal template and variant information about your gene of focus.
We will prioritise proposals for platforms that:
- Are already established and scalable; however new platforms will also be considered.
- Can achieve clinically relevant turnaround (6-12 months).
- Can leverage appropriate expertise as well as cash and/or in-kind contribution.
- Have the potential to be cost efficient and scaled to resolve multiple VUS identified through diagnostic testing in the future.
Applications should consider the stringency of evidence required to elevate a variant from VUS (3) to likely pathogenic/pathogenic (4/5) in their proposal (see Brnich et al. Genome Medicine (2020) 12:3).
Projects will be eligible for catalyst funding of up to $200,000. If your application is short-listed, you will be invited to participate in an interview with our panel to discuss your proposal and budget before a final decision is released.
We encourage researchers to utilise existing capabilities in their project design. Phenomics Australia is an NCRIS-funded initiative that offers services and expertise in developing animal models and non-animal technologies to assist project development and delivery.
For more information, contact John Parisot at j.parisot@therapeuticinnovation.com.au or visit:
In Vivo Genome Engineering & Disease Modelling
In Vitro Genome Engineering & Disease Modelling Service
Proposals must be submitted to functional.genomics@mcri.edu.au
Applications close at 5PM (AEDT) on Monday March 27th, 2023