Accès libre

In Silico Analysis of Novel Titin Non-Synonymous Missense Variants Detected by Targeted Next-Generation Sequencing in a Cohort of Romanian Index Patients with Hypertrophic Cardiomyopathy

Miruna Mihaela Micheu
Miruna Mihaela Micheu
, 
Nicoleta Oprescu
Nicoleta Oprescu
 et 
Nicoleta-Monica Popa-Fotea
Nicoleta-Monica Popa-Fotea
   | 05 mai 2022
Romanian Journal of Cardiology's Cover Image
À propos de cet article
Article précédent
Article suivant
Citez
Article Category: Original Article
Publié en ligne: 05 mai 2022
Pages: 565 - 571
DOI: https://doi.org/10.47803/rjc.2021.31.3.565
Mots clés
© 2021 Miruna Mihaela Micheu et al., published by Sciendo
This work is licensed under the Creative Commons Attribution 4.0 International License.

Figure 1

Bioinformatic filtering strategy to identify variants for further prioritization. From total TTN variants passing quality filters were retrieved the coding ones with allele frequency < 0.1% in population databases. Furthermore, only nonsynonymous missense variants were recovered and manually searched through population databases and repositories. Seven novel TTN nonsynonymous missense variants were selected for prioritization.
Bioinformatic filtering strategy to identify variants for further prioritization. From total TTN variants passing quality filters were retrieved the coding ones with allele frequency < 0.1% in population databases. Furthermore, only nonsynonymous missense variants were recovered and manually searched through population databases and repositories. Seven novel TTN nonsynonymous missense variants were selected for prioritization.

Figure 2

Variant prioritizing strategy for further experimental investigation. From 7 novel TTN nonsynonymous missense variants, 4 were predicted to be possibly pathogenic by M-CAP and entered second prediction. Finally, 3 TTN variants were identified as likely function-impacting variants.
Variant prioritizing strategy for further experimental investigation. From 7 novel TTN nonsynonymous missense variants, 4 were predicted to be possibly pathogenic by M-CAP and entered second prediction. Finally, 3 TTN variants were identified as likely function-impacting variants.

General and echocardiographic characteristics of HCM subjects

Variable Overall cohort (n = 45) TTN+ (n = 13) TTN− (n = 32) p
Age at inclusion, years 51±15.5 54.31±14 49.34±15.84 0.34
Male sex, n (%) 33 (73.3%) 10 (76.9%) 23 (71.9%) 0.72
Family history of HCM, n (%) 7 (15.56%) 4 (30.77%) 3 (9.4%) 0.47
Family history of SCD, n (%) 14 (31.1%) 3 (23.1%) 11 (34.4%) 0.45
ICD, n (%) 7 (15.56%) 3 (23.1%) 4 (12.5 %) 0.56
Atrial fibrillation, n (%) 22 (48.9%) 7 (53.8%) 15 (46.9%) 0.67
Maron classification, n (%) 0.32
  1 7 (15.56%) 1 (7.7%) 6 (18.8%)
  2 5 (11.1%) 2 (15.4%) 3 (9.4%)
  3 32 (71.1%) 9 (69.2%)) 23 (71.9%)
  4 1 (2.2%) 1 (7.7%) 0
Presence of LVOTO, n (%) 20 (44.44%) 7 (53.9%) 13 (40.6%) 0.53
LV maximal wall thickness, mm 20.8±5.2 20.61±6.58 20.69±4.58 0.32
LV mass, g 279.91±90.72 297±90.62 272.04±91.6 0.51
LVEDD, mm 41.21±7.87 42.72±7.49 40.59±8.07 0.44
LVESD, mm 25.31±9.77 24.18±5.27 25.83±111.32 0.98
LVEDV, ml 111.42±39.6 125.55±45.8 106.12±36.68 0.41
LVESV, ml 55.55±30.13 55.69±32.56 56.74±29.63 0.98
LVEF, % 57.09±7.64 56.35±5.86 57.39±7.12 0.66
LAD, mm 40.92±6.86 41.09±8.69 40.85±6.13 0.88
LAV, ml 90.32±41.75 87.5±41.06 91.42±42.75 0.68

Novel TTN nonsynonymous missense variants detected in our cohort

Gene HGVSc HGVSp Exon Region
TTN c.44530G>T p.Ala14844Ser 242 I-band
TTN c.30392G>T p.Cys10131Phe 108 I-band
TTN c.25185G>T p.Lys8395Asn 88 I-band
TTN c.16783G>T p.Val5595Leu 58 I-band
TTN c.11927A>G p.Lys3976Arg 49 I-band
TTN c.2518G>T p.Ala840Ser 16 near Z-disk
TTN c.49G>T p.Val17Leu 2 Z-disk
eISSN:
2734-6382
Langue:
Anglais
Périodicité:
4 fois par an
Sujets de la revue:
Medicine, Clinical Medicine, Internal Medicine, Cardiology, Pediatrics and Juvenile Medicine, Paediatric Cardiology, Surgery, Cardiac Surgery
RSS Feed de la revue