Hereditary Transthyretin Amyloidosis in Patients Referred to a Genetic Testing Program
Bibliographic record
Abstract
Background Diagnosis of hereditary amyloid transthyretin (hATTR) amyloidosis with cardiomyopathy is frequently delayed, in large part because of symptom overlap with other cardiovascular diseases and limited provider knowledge of this disease. The sponsored and provider referred hATTR Compass Genetic Testing Program (Ionis, Carlsbad, CA; Ambry Genetics, Aliso Viejo, CA) provided no‐cost genetic testing to adults with a family history or clinical suspicion of hATTR amyloidosis. This study aims to characterize patients with hATTR amyloidosis and increase awareness of genetic testing for hATTR. Methods and Results Patients were referred to the hATTR genetic testing program, and a cross‐sectional post hoc analysis was performed. A pathogenic TTR variant was identified in 1503 (6.6%) of 22 886 patients referred for genetic testing between June 2018 and March 2022. Patients were identified in all US states, 3 US territories, and Canada. Median age at testing was 63 years, and 44% were female. The p.V142I TTR variant was the most common (n=1263, 84.0%). Only 32% of patients with a pathogenic TTR variant reported a known family history; a lower percentage of Black individuals reported a known family history compared with other racial and ethnic groups. Black patients accounted for 23.7% of all patients referred and 81.9% of patients with the p.V142I variant. Conclusions This sponsored genetic testing program identified a large number of patients with a pathogenic TTR variant, notably, in geographic regions not previously reported, and demographic groups that are historically underrepresented in the literature.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".