Austin, Rachel and Brown, Jaye S. and Casauria, Sarah and Madelli, Evanthia O. and Mattiske, Tessa and Boughtwood, Tiffany and Metke, Alejandro and Davis, Andrew and Horton, Ari E. and Winlaw, David and Das, Debjani and Soka, Magdalena and Giannoulatou, Eleni and Rath, Emma M. and Haan, Eric and Blue, Gillian M. and Vohra, Jitendra and Atherton, John J. and van Spaendonck-Zwarts, Karin and Cox, Kathy and Burnett, Leslie and Wallis, Mathew and Haas, Matilda and Quinn, Michael C.J. and Pachter, Nicholas and Poplawski, Nicola K. and Stark, Zornitza and Bagnall, Richard D. and Weintraub, Robert G. and Pantaleo, Sarah-Jane and Lunke, Sebastian and De Fazio, Paul and Thompson, Tina and James, Paul and Chang, Yuchen and Fatkin, Diane and Macciocca, Ivan and Ingles, Jodie and Dunwoodie, Sally L. and Semsarian, Chris and McGaughran, Julie and Ades, Lesley and Enriquez, Annabel and McLean, Alison and Smyth, Renee and Alankarage, Dimithu and Fatkin, Diane and McNamara, James and Soka, Magdalena and Almog, Morgan and Fear, Vanessa and Medi, Caroline and Stark, Zornitza and Al-Shinnag, Mohammad and Fine, Miriam and Metke, Alejandro and Sy, Raymond and Atherton, John J. and Finlay, Keri and Milnes, Di and Tang, Dotti and Austin, Rachel and Garza, Denisse and Milward, Michael and Taylor, Jessica and Bagnall, Richard D. and Giannoulatou, Eleni and Morrish, Ansley and Taylor, Shelby and Barnett, Chris and Gongolidis, Laura and Morwood, Jim and Tchan, Michel and Blue, Gillian M. and Gray, Belinda and Mountain, Helen and Thompson, Tina and Bodek, Simon and Greer, Cassie and Mowat, David and Thorpe, Jordan and Boggs, Kirsten and Haan, Eric and Ng, Chai-Ann and Trainer, Alison and Bogwitz, Michael and Haas, Mathilda and Nowak, Natalie and Trivedi, Gunjan and Boughtwood, Tiffany and Hanna, Bernadette and Martinez, Noelia Nunez and Valente, Giulia and Bray, Alessandra and Harvey, Richard and Ohanian, Monique and van Spaendonck-Zwarts, Karin and Brion, Marie-Jo and Hayward, Janette and O’Sullivan, Sinead and Vandenberg, Jamie and Brown, Jaye and Herrera, Carmen and Overkov, Angela and Verma, Kunal and Richardson, Rob Bryson and Hill, Adam and Pachter, Nicholas and Vidgen, Miranda and Burnett, Leslie and Hollingsworth, Georgie and Patel, Chirag and Vohra, Jitendra and Burns, Charlotte and Hollway, Georgina and Perrin, Mark and Waddel-Smith, Kathryn and Cao, Michelle and Horton, Ari E. and Perry, Matthew and Wallis, Mathew and Carr, Will and Howting, Denise and Pflaumer, Andreas and Weintraub, Robert G. and Casauria, Sarah and Ingles, Jodie and Phillips, Peta and Wilson, Meredith and Chalinor, Heather and Isbister, Joanne and Phuong, Thuan and Winlaw, David and Chang, Yuchen and Jackson, Matilda and Pope-Couston, Rachel and Worgan, Lisa and Chapman, Gavin and James, Paul and Poplawski, Nicola K. and Wornham, Linda and Charitou, Theosodia and Jane-Pantaleo, Sarah and Punni, Preeti and Wu, Kathy and Chong, Belinda and Johnson, Renee and Quinn, Michael C.J. and Yeates, Laura and Collins, Felicity and Kelly, Andrew and Quinn, Michael and Zentner, Dominica and Correnti, Gemma and King-Smith, Sarah and Rajagopalan, Sulekha and Cox, Kathy and Kirk, Edwin and Raju, Hariharan and Cunningham, Fiona and Kummerfeld, Sarah and Rath, Emma M. and Das, Debjani and Lassman, Timo and Regan, Matthew and Davis, Jason and Lipton, Jonathon and Rogers, Jonathan and Davis, Andrew and Lunke, Sebastian and Ryan, Mark and De Fazio, Paul and Macciocca, Ivan and Sandaradura, Sarah and de Silva, Michelle and MacIntyre, Paul and Schonrock, Nicole and Den Elzen, Nicola and Madelli, Evanthia O. and Scuffham, Paul and Devery, Sophie and Mallawaarachchi, Amali and Semsarian, Chris and Dobbins, Julia and Mansour, Julia and Sherburn, Isabella and Dunwoodie, Sally L. and Martin, Ellenore and Sherlock, Mary-Clare and Dwyer, Nathan and Mathew, Jacob and Singer, Emma and Elbracht-Leong, Stefanie and Mattiske, Tessa and Smerdon, Carla and Elliott, David and McGaughran, Julie and Smith, Janine (2024) A multitiered analysis platform for genome sequencing: Design and initial findings of the Australian Genomics Cardiovascular Disorders Flagship. Genetics in Medicine Open, 2. p. 101842. ISSN 29497744
Full text not available from this repository.Abstract
PURPOSE: The Australian Genomics Cardiovascular Disorders Flagship was a national multidisciplinary collaboration. It aimed to investigate the feasibility of genome sequencing (GS) and functional genomics to resolve variants of uncertain significance (VUS) in the clinical management of patients and families with cardiomyopathies, primary arrhythmias, and congenital heart disease (CHD). METHODS: Between April 2019 and December 2021, 600 probands meeting cardiovascular disorder criteria from 17 cardiology and genetics clinics across Australia were enrolled in the Flagship and underwent GS. The Flagship adopted a tiered approach to GS analysis. Tier 1 analysis assessed genes with established clinical validity for each cardiovascular condition. Tier 2 analysis assessed lesser-evidenced research-based genes. Tier 3 analysis assessed the functional impact of VUS that remained after tier 1 and tier 2 analysis. RESULTS: Overall, a pathogenic or likely pathogenic variant was identified in 41% of participants with a cardiomyopathy, 40% with an arrhythmia syndrome, and 15% with a familial CHD/CHD+Extra Cardiac Anomalies. A VUS outcome ranged from 13% for arrhythmias to 34% for CHD/CHD+Extra Cardiac Anomalies participants. Tier 2 research analysis identified a likely pathogenic/pathogenic variant for a further 15 participants and a VUS for an additional 15 participants. CONCLUSION: The Flagship successfully facilitated a model of care that harnesses clinical GS and functional genomics for the resolution of VUS in the clinical setting. This valuable data set can be used to inform clinical practice and facilitate research into the future.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 02 May 2025 04:35 |
| Last Modified: | 02 May 2025 04:35 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/1629 |
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