Pathogenic germline variants in ACVRL1, ENG, and SMAD4 are associated with hereditary hemorrhagic telangiectasia (HHT, MIM: 600376, 187300) and juvenile polyposis syndrome/HHT (JPS/HHT, MIM: 175050). HHT is an autosomal dominant vascular dysplasia characterized by small vascular lesions (telangiectases) and larger vascular legions (arteriovenous malformations (AVMs)) in characteristic locations (telangiectases in the oral and nasal mucosa, lips, fingers, upper intestinal tract; AVMs in the lungs, liver and brain). This expert panel will provide assessment regarding the pathogenicity of variants in ACVRL1, ENG, and SMAD4 with respect to HHT disease. Specifically, we will develop a set of HHT rule specifications of the ACMG/AMP guidelines with individual gene specifications where needed. We will first focus our efforts on curating variants that are currently in ClinVar, and then we will expand our efforts to curating variants from other HHT databases and submit those to ClinVar.
|Pinar Bayrak-Toydemir, MD, PhD, FACMG||Executive Leadership|
|Jamie McDonald, MS, LCGC||Executive Leadership|
|Desiree DeMille, PhD||Coordinator|
|Helen M. Arthur, PhD||Member|
|Carmelo Bernabéu, PhD||Member|
|Murray Brillant, PhD||Member|
|Sophie Dupuis-Girod, MD, PhD||Member|
|Arupa Ganguly, PhD, FACMG||Member|
|Sophie Giraud, MD, PhD||Member|
|Jaime Jessen, BSc, MSc, CGC, CCGC||Member|
|Raj Kasthuri, MBBS, MD||Member|
|Hans Kristian Ploos van Amstel, PhD, VKGL, ErCLG/EBMG||Member|
|Carla Olivieri, PhD||Member|
|Reed E. Pyeritz, MD, PhD, ABIM/ABMG||Member|
|Hilary Racher, PhD, DABMGG, FACMG, FCCMG||Member|
|Pernille Tørring, MD, PhD||Member|
|Claire L. Shovlin, MB BChir, PhD, FRCP||Member|
Please contact a coordinator if you have questions.
A systematic process of evaluating evidence to classify a genomic variant on a spectrum from pathogenic to benign with respect to a particular disease and inheritance pattern.