**Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.**
Amy R. Kontorovich, MD, PhD
The Cardiovascular Research Institute, The Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, New York, NY, 10029 USA

**Main Body of the Abstract**
Purpose: Previous studies have established a set of “red flags” for hereditary transthyretin amyloidosis (hATTR) but these have not been specifically evaluated for the most common pathogenic TTR variant, c.424G>A, p.Val142Ile (V142I), found in 4% of individuals with African ancestry. Here, we evaluated clinical features among carriers of TTR V142I in an ancestrally diverse electronic health record (EHR)-linked biobank.
Methods: We evaluated nine clinical features among V142I positive and negative individuals using EHR and exome sequence data from 27,630 unrelated adult biobank participants.
Results: Among 337 V142I positive individuals (median age 63, 60% female), ten (3.0%) were diagnosed with amyloidosis. V142I was associated with an increased risk for the previously established red flags cardiomyopathy or heart failure (CM/HF), polyneuropathy (PN) and carpal tunnel syndrome, as well as atrial fibrillation and proteinuria, but only in individuals ≥ age 60. Of these, CM/HF emerged earliest. By age 50, the cumulative incidence of CM/HF was 3.5-fold higher in V142I positive vs. negative individuals. V142I positive individuals had evidence of hATTR-related clinical features 1.7 to 7.7 years earlier than variant negative individuals, with a 2-fold higher cumulative incidence of CM/HF, PN and proteinuria by age 60. Spinal stenosis, biceps tendon rupture and autonomic dysfunction were not associated with V142I or occurred at exceedingly low frequencies.
Conclusions: This study clarifies red flags that are and are not associated with V142I in an age-dependent manner. With modifying therapies available, early diagnosis of hATTR in V142I positive individuals through recognition of key clinical features is paramount.



**Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.**
Amy R. Kontorovich, MD, PhD
The Cardiovascular Research Institute, The Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, New York, NY, 10029 USA

**Main Body of the Abstract**
**Purpose:** Previous studies have established a set of “red flags” for hereditary transthyretin amyloidosis (hATTR) but these have not been specifically evaluated for the most common pathogenic _TTR_ variant, c.424G>A, p.Val142Ile (V142I), found in 4% of individuals with African ancestry. Here, we evaluated clinical features among carriers of _TTR_ V142I in an ancestrally diverse electronic health record (EHR)-linked biobank.
**Methods:** We evaluated nine clinical features among V142I positive and negative individuals using EHR and exome sequence data from 27,630 unrelated adult biobank participants.
**Results:** Among 337 V142I positive individuals (median age 63, 60% female), ten (3.0%) were diagnosed with amyloidosis. V142I was associated with an increased risk for the previously established red flags cardiomyopathy or heart failure (CM/HF), polyneuropathy (PN) and carpal tunnel syndrome, as well as atrial fibrillation and proteinuria, but only in individuals ≥ age 60. Of these, CM/HF emerged earliest. By age 50, the cumulative incidence of CM/HF was 3.5-fold higher in V142I positive _vs._ negative individuals. V142I positive individuals had evidence of hATTR-related clinical features 1.7 to 7.7 years earlier than variant negative individuals, with a 2-fold higher cumulative incidence of CM/HF, PN and proteinuria by age 60. Spinal stenosis, biceps tendon rupture and autonomic dysfunction were not associated with V142I or occurred at exceedingly low frequencies.
**Conclusions:** This study clarifies red flags that are and are not associated with V142I in an age-dependent manner. With modifying therapies available, early diagnosis of hATTR in V142I positive individuals through recognition of key clinical features is paramount.



Evolving knowledge of “red flag” clinical features associated with TTR p.Val142Ile in a diverse electronic health record-linked biobank PA13 (#544)

We invite you to attend the XIX International Symposium on Amyloidosis to be held in Rochester, MN.

This symposium is organized as a hybrid meeting (with the focus on in-person) held from Sunday, May 26 through Thursday, May 30, 2024.

Together with the ISA Board and members of Mayo Clinic, a very attractive scientific hybrid program is being planned. The program will cover a variety of types of systemic amyloidosis: ATTR (hereditary and wild-type), AL (light-chain), AA and less frequent forms. There will be key lectures, specific symposia including those company sponsored, oral presentations and poster sessions of accepted abstracts.

COURSE DESCRIPTION
This program will provide a comprehensive review of state-of-the-art education in systemic amyloidosis: basic science, pathophysiology, diagnosis, current and emerging treatments. Scientific presentations will include competitive oral and poster abstracts. The rapid evolution of scientific discovery and expanding treatment options has created tremendous interest in the field and this meeting will fill and important gap in educating scientists and clinicians.