Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 4738 | 14437;14438;14439 | chr2:178738241;178738240;178738239 | chr2:179602968;179602967;179602966 |
| N2AB | 4421 | 13486;13487;13488 | chr2:178738241;178738240;178738239 | chr2:179602968;179602967;179602966 |
| N2A | 3494 | 10705;10706;10707 | chr2:178738241;178738240;178738239 | chr2:179602968;179602967;179602966 |
| N2B | 4375 | 13348;13349;13350 | chr2:178738241;178738240;178738239 | chr2:179602968;179602967;179602966 |
| Novex-1 | 4500 | 13723;13724;13725 | chr2:178738241;178738240;178738239 | chr2:179602968;179602967;179602966 |
| Novex-2 | 4567 | 13924;13925;13926 | chr2:178738241;178738240;178738239 | chr2:179602968;179602967;179602966 |
| Novex-3 | None | None | chr2:None | chr2:None |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | None | None | 0.13 | N | 0.34 | 0.221 | 0.310147130316 | gnomAD-4.0.0 | 1.59182E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43303E-05 | 0 |
| R/Q | rs553541436  |
0.22 | 0.142 | N | 0.285 | 0.094 | 0.19670166235 | gnomAD-2.1.1 | 2.5E-05 | None | None | None | None | I | None | 8.27E-05 | 0 | None | 0 | 5.16E-05 | None | 3.27E-05 | None | 0 | 2.34E-05 | 0 |
| R/Q | rs553541436 |
0.22 | 0.142 | N | 0.285 | 0.094 | 0.19670166235 | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | I | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 9.42E-05 | 0 | 7.35E-05 | 0 | 0 |
| R/Q | rs553541436 |
0.22 | 0.142 | N | 0.285 | 0.094 | 0.19670166235 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/Q | rs553541436 |
0.22 | 0.142 | N | 0.285 | 0.094 | 0.19670166235 | gnomAD-4.0.0 | 1.03497E-04 | None | None | None | None | I | None | 5.33262E-05 | 1.667E-05 | None | 0 | 6.70181E-05 | None | 3.12578E-05 | 0 | 1.25452E-04 | 3.29475E-05 | 9.60523E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.565 | likely_pathogenic | 0.6816 | pathogenic | 0.058 | Stabilizing | 0.016 | N | 0.317 | neutral | None | None | None | None | I |
| R/C | 0.4145 | ambiguous | 0.5308 | ambiguous | -0.222 | Destabilizing | 0.864 | D | 0.245 | neutral | None | None | None | None | I |
| R/D | 0.8034 | likely_pathogenic | 0.8725 | pathogenic | -0.226 | Destabilizing | 0.072 | N | 0.391 | neutral | None | None | None | None | I |
| R/E | 0.4169 | ambiguous | 0.5347 | ambiguous | -0.176 | Destabilizing | 0.016 | N | 0.272 | neutral | None | None | None | None | I |
| R/F | 0.7562 | likely_pathogenic | 0.8295 | pathogenic | -0.231 | Destabilizing | 0.356 | N | 0.321 | neutral | None | None | None | None | I |
| R/G | 0.4283 | ambiguous | 0.5604 | ambiguous | -0.1 | Destabilizing | 0.13 | N | 0.34 | neutral | N | 0.511657503 | None | None | I |
| R/H | 0.1763 | likely_benign | 0.215 | benign | -0.568 | Destabilizing | None | N | 0.193 | neutral | None | None | None | None | I |
| R/I | 0.3795 | ambiguous | 0.4887 | ambiguous | 0.431 | Stabilizing | 0.001 | N | 0.259 | neutral | None | None | None | None | I |
| R/K | 0.0903 | likely_benign | 0.11 | benign | -0.114 | Destabilizing | None | N | 0.204 | neutral | None | None | None | None | I |
| R/L | 0.4153 | ambiguous | 0.5263 | ambiguous | 0.431 | Stabilizing | 0.03 | N | 0.308 | neutral | N | 0.508561728 | None | None | I |
| R/M | 0.3356 | likely_benign | 0.4534 | ambiguous | -0.026 | Destabilizing | 0.356 | N | 0.278 | neutral | None | None | None | None | I |
| R/N | 0.6545 | likely_pathogenic | 0.7469 | pathogenic | -0.017 | Destabilizing | 0.072 | N | 0.269 | neutral | None | None | None | None | I |
| R/P | 0.9592 | likely_pathogenic | 0.9748 | pathogenic | 0.325 | Stabilizing | 0.232 | N | 0.365 | neutral | D | 0.642347882 | None | None | I |
| R/Q | 0.1318 | likely_benign | 0.1664 | benign | -0.065 | Destabilizing | 0.142 | N | 0.285 | neutral | N | 0.497957901 | None | None | I |
| R/S | 0.6263 | likely_pathogenic | 0.7512 | pathogenic | -0.241 | Destabilizing | 0.016 | N | 0.345 | neutral | None | None | None | None | I |
| R/T | 0.3355 | likely_benign | 0.454 | ambiguous | -0.076 | Destabilizing | 0.001 | N | 0.212 | neutral | None | None | None | None | I |
| R/V | 0.4607 | ambiguous | 0.5725 | pathogenic | 0.325 | Stabilizing | None | N | 0.248 | neutral | None | None | None | None | I |
| R/W | 0.3294 | likely_benign | 0.4092 | ambiguous | -0.382 | Destabilizing | 0.864 | D | 0.242 | neutral | None | None | None | None | I |
| R/Y | 0.626 | likely_pathogenic | 0.7067 | pathogenic | 0.032 | Stabilizing | 0.214 | N | 0.343 | neutral | None | None | None | None | I |
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.