*3.3. Penetrance of Cardiolaminopathy Indicators*

Penetrance of cardiac disorders along with abnormal levels of cardiac biomarkers was age dependent (Figure 3). During lifespan, the earliest abnormality, emerging in the second decade of life in 12% of *LMNA* variant carriers and in the third decade in 27%, was hsTnT level >14 ng/L, followed by the presence of AVB and HF (each 5% in the 2nd and 15% in the 3rd decade of life) and MVA (2% and 13%, respectively). Penetrance of cardiolaminopathy indicators was nearly complete in the 7th

decade of life with 98% of patients presenting with AVB, 100% with SVA, 90% with HF, 92% with serum biomarker hsTnT >14 ng/L, and 100% with NT-proBNP >125 pg/mL.

**Figure 3.** Penetrance of cardiolaminopathy indicators. Legend: AVB: atrioventricular block; HF: heart failure; hs: highly sensitive; MVA: malignant ventricular arrhythmia; NT-proBNP: N-terminal pro-brain natriuretic peptide; SVA: supraventricular arrhythmia.

During the follow-up, there was a modest but significant increase in the hsTnT level (Table 3), possibly reflecting progressive myocardial damage. The change in NT-proBNP level was much more noticeable, reflecting that HF was more common and advanced at the end of the follow-up period. Changes in cardiac biomarkers' concentrations measured during the initial and subsequent visits in patients with two or more measurements are shown in Figures S2 and S3.

**Table 3.** Change in circulating biomarkers' levels between baseline and last measurement.


The results are shown as median and quartiles (Q1:25th–Q2:75th percentiles). Legend: hs Troponin T: highly sensitive troponin T; NT-proBNP: N-terminal prohormone brain natriuretic peptide.
