Key result
Healthy Russian men carry TTN missense variants at ~15% frequency with no pathogenic variants identified.
Why the study?
Data on the spectrum and frequency of TTN variants in the healthy Russian population are lacking, which complicates variant interpretation in patients with heart pathology.
Cross-Sectional (n=192)
Establishing the baseline frequency of TTN variants in a healthy population is crucial for accurately interpreting genetic testing results in patients with cardiomyopathies.
Provides reference TTN variant frequencies in healthy men; leaves open broader validation for cardiomyopathy diagnostics.
Background . Gene TTN associated with all types of cardiomyopathy, however its large size (294 b.p.) warrants a lot of individual unique genetic variants or variants with low frequency, that aggravates their interpretation. Besides that nowadays there is no data about spectrum of variants in this gene in healthy Russian population. Recognition frequency and spectrum of variants in gene TTN in healthy Russian population will allow us to use it for interpretation results of molecular genetic research for patients with different heart pathology, and define prognosis for different heart diseases. Objective . Recognize frequency and spectrum of single nucleotide and truncating variants in gene TTN in healthy Russian population and compare it with international data bases, and evaluate level of pathogenicity these variants and their distributing across titin structure. Design and methods. 192 men in age 55,8±6,6 years were tested with next-generation sequencing. Identified genetic variants were confirmed by Sanger sequencing. Results. Allele missense variant frequency (with frequency less than 0.1%) in TTN in healthy Russian population amount to 15.1 %, and truncating variants — 0.52 %. 37,9 % of them were variants of unknown significance, 62 % — likely-benign and 0.1 % — benign. There was no pathological and likely-pathological variants. Identified genetic variants distributed throughout the titin structure. Conclusion . Received result is congruent с international data bases and researches. Expended laboratory method (Next generation sequencing and confirmation with Sanger sequencing) can be used both in clinical practice, and in creating data bases of genetic variants in healthy Russian population.
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Vakhrushev et al. (2021) conducted a cross-sectional in healthy Russian population (n=192). TTN genetic variants was evaluated on Frequency of allele missense and truncating variants in the TTN gene. TTN genetic variants had an allele missense frequency of 15.1% and a truncating variant frequency of 0.52% in healthy Russian men, with no pathogenic variants identified.
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