Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2896 | 8911;8912;8913 | chr2:178769895;178769894;178769893 | chr2:179634622;179634621;179634620 |
| N2AB | 2896 | 8911;8912;8913 | chr2:178769895;178769894;178769893 | chr2:179634622;179634621;179634620 |
| N2A | 2896 | 8911;8912;8913 | chr2:178769895;178769894;178769893 | chr2:179634622;179634621;179634620 |
| N2B | 2850 | 8773;8774;8775 | chr2:178769895;178769894;178769893 | chr2:179634622;179634621;179634620 |
| Novex-1 | 2850 | 8773;8774;8775 | chr2:178769895;178769894;178769893 | chr2:179634622;179634621;179634620 |
| Novex-2 | 2850 | 8773;8774;8775 | chr2:178769895;178769894;178769893 | chr2:179634622;179634621;179634620 |
| Novex-3 | 2896 | 8911;8912;8913 | chr2:178769895;178769894;178769893 | chr2:179634622;179634621;179634620 |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs72647884  |
-0.432 | 1.0 | D | 0.717 | 0.513 | 0.611931882649 |
Taylor (2011)
Anderson (2013)
Bogolomovas (2016)
Fleming (2021)
| None |
ARVC 
|
het | None | None | N | Genetic analysis of TTN in 38 ARVC families; complete segregation in 3-generation family (n = 7, 7 affected (total 11)); Strong destabilisation of domain in vitro; altered conformational dynamics of tandem in silico; echocardiography of knock-in mice show mild diastolic dysfunction / myocardial stiffness; MD characterisation of variants at the T2896 position | None | None | None | None | None | None | None | None | None | None | None |
| T/I | rs72647884 |
-0.432 | 1.0 | D | 0.717 | 0.513 | 0.611931882649 | gnomAD-4.0.0 | 1.59054E-06 | None | None | None | None | N | None | 5.65227E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.2043 | likely_benign | 0.2426 | benign | -0.429 | Destabilizing | 0.999 | D | 0.655 | neutral | N | 0.503754376 | None | None | N |
| T/C | 0.6623 | likely_pathogenic | 0.7371 | pathogenic | -0.215 | Destabilizing | 1.0 | D | 0.758 | deleterious | None | None | None | None | N |
| T/D | 0.525 | ambiguous | 0.614 | pathogenic | -0.019 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| T/E | 0.4629 | ambiguous | 0.5444 | ambiguous | -0.097 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| T/F | 0.5577 | ambiguous | 0.6511 | pathogenic | -0.9 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| T/G | 0.2395 | likely_benign | 0.2822 | benign | -0.566 | Destabilizing | 1.0 | D | 0.661 | neutral | None | None | None | None | N |
| T/H | 0.4564 | ambiguous | 0.534 | ambiguous | -0.866 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | N |
| T/I | 0.6473 | likely_pathogenic | 0.7082 | pathogenic | -0.186 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | D | 0.565786243 | None | None | N |
| T/K | 0.3872 | ambiguous | 0.4805 | ambiguous | -0.412 | Destabilizing | 1.0 | D | 0.718 | prob.delet. | None | None | None | None | N |
| T/L | 0.232 | likely_benign | 0.2752 | benign | -0.186 | Destabilizing | 0.999 | D | 0.727 | prob.delet. | None | None | None | None | N |
| T/M | 0.1178 | likely_benign | 0.1385 | benign | 0.108 | Stabilizing | 1.0 | D | 0.766 | deleterious | None | None | None | None | N |
| T/N | 0.135 | likely_benign | 0.1642 | benign | -0.173 | Destabilizing | 1.0 | D | 0.702 | prob.neutral | N | 0.496745121 | None | None | N |
| T/P | 0.6224 | likely_pathogenic | 0.689 | pathogenic | -0.238 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | N | 0.497868613 | None | None | N |
| T/Q | 0.345 | ambiguous | 0.4147 | ambiguous | -0.451 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| T/R | 0.3288 | likely_benign | 0.4307 | ambiguous | -0.077 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| T/S | 0.1868 | likely_benign | 0.2146 | benign | -0.383 | Destabilizing | 0.999 | D | 0.668 | neutral | N | 0.497822157 | None | None | N |
| T/V | 0.4967 | ambiguous | 0.554 | ambiguous | -0.238 | Destabilizing | 0.999 | D | 0.688 | prob.neutral | None | None | None | None | N |
| T/W | 0.8242 | likely_pathogenic | 0.8809 | pathogenic | -0.88 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| T/Y | 0.536 | ambiguous | 0.6424 | pathogenic | -0.612 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | N |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.