Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31159 | 93700;93701;93702 | chr2:178548151;178548150;178548149 | chr2:179412878;179412877;179412876 |
| N2AB | 29518 | 88777;88778;88779 | chr2:178548151;178548150;178548149 | chr2:179412878;179412877;179412876 |
| N2A | 28591 | 85996;85997;85998 | chr2:178548151;178548150;178548149 | chr2:179412878;179412877;179412876 |
| N2B | 22094 | 66505;66506;66507 | chr2:178548151;178548150;178548149 | chr2:179412878;179412877;179412876 |
| Novex-1 | 22219 | 66880;66881;66882 | chr2:178548151;178548150;178548149 | chr2:179412878;179412877;179412876 |
| Novex-2 | 22286 | 67081;67082;67083 | chr2:178548151;178548150;178548149 | chr2:179412878;179412877;179412876 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/L | rs765476463  |
-0.312 | None | N | 0.071 | 0.194 | 0.270001397563 | gnomAD-2.1.1 | 8.03E-06 | None | None | None | None | I | None | 0 | 2.9E-05 | None | 0 | 5.56E-05 | None | 0 | None | 0 | 0 | 0 |
| F/L | rs765476463 |
-0.312 | None | N | 0.071 | 0.194 | 0.270001397563 | gnomAD-4.0.0 | 1.11375E-05 | None | None | None | None | I | None | 0 | 2.28634E-05 | None | 0 | 1.66352E-04 | None | 0 | 0 | 0 | 0 | 0 |
| F/S | rs1469115773 |
None | 0.086 | N | 0.383 | 0.216 | 0.37568098594 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| F/V | None | None | None | N | 0.151 | 0.207 | 0.337378238328 | gnomAD-4.0.0 | 1.59107E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85796E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.1415 | likely_benign | 0.1183 | benign | -0.601 | Destabilizing | 0.051 | N | 0.336 | neutral | None | None | None | None | I |
| F/C | 0.1048 | likely_benign | 0.0991 | benign | -0.282 | Destabilizing | 0.958 | D | 0.263 | neutral | N | 0.437460503 | None | None | I |
| F/D | 0.2278 | likely_benign | 0.1904 | benign | 0.662 | Stabilizing | 0.223 | N | 0.331 | neutral | None | None | None | None | I |
| F/E | 0.2932 | likely_benign | 0.2654 | benign | 0.623 | Stabilizing | 0.111 | N | 0.418 | neutral | None | None | None | None | I |
| F/G | 0.278 | likely_benign | 0.2444 | benign | -0.728 | Destabilizing | 0.2 | N | 0.408 | neutral | None | None | None | None | I |
| F/H | 0.1648 | likely_benign | 0.1602 | benign | 0.343 | Stabilizing | 0.004 | N | 0.245 | neutral | None | None | None | None | I |
| F/I | 0.0722 | likely_benign | 0.068 | benign | -0.309 | Destabilizing | 0.086 | N | 0.249 | neutral | N | 0.395805881 | None | None | I |
| F/K | 0.2111 | likely_benign | 0.2267 | benign | 0.016 | Stabilizing | 0.002 | N | 0.183 | neutral | None | None | None | None | I |
| F/L | 0.431 | ambiguous | 0.4353 | ambiguous | -0.309 | Destabilizing | None | N | 0.071 | neutral | N | 0.379142918 | None | None | I |
| F/M | 0.2036 | likely_benign | 0.2021 | benign | -0.403 | Destabilizing | 0.83 | D | 0.243 | neutral | None | None | None | None | I |
| F/N | 0.1445 | likely_benign | 0.134 | benign | -0.002 | Destabilizing | 0.008 | N | 0.197 | neutral | None | None | None | None | I |
| F/P | 0.849 | likely_pathogenic | 0.8211 | pathogenic | -0.389 | Destabilizing | 0.738 | D | 0.382 | neutral | None | None | None | None | I |
| F/Q | 0.2032 | likely_benign | 0.2124 | benign | -0.01 | Destabilizing | 0.022 | N | 0.215 | neutral | None | None | None | None | I |
| F/R | 0.1661 | likely_benign | 0.1738 | benign | 0.306 | Stabilizing | 0.002 | N | 0.206 | neutral | None | None | None | None | I |
| F/S | 0.1 | likely_benign | 0.0809 | benign | -0.532 | Destabilizing | 0.086 | N | 0.383 | neutral | N | 0.36215188 | None | None | I |
| F/T | 0.1126 | likely_benign | 0.0949 | benign | -0.486 | Destabilizing | 0.008 | N | 0.171 | neutral | None | None | None | None | I |
| F/V | 0.0711 | likely_benign | 0.0653 | benign | -0.389 | Destabilizing | None | N | 0.151 | neutral | N | 0.373371739 | None | None | I |
| F/W | 0.3475 | ambiguous | 0.3417 | ambiguous | -0.388 | Destabilizing | 0.968 | D | 0.285 | neutral | None | None | None | None | I |
| F/Y | 0.0832 | likely_benign | 0.0743 | benign | -0.311 | Destabilizing | 0.302 | N | 0.297 | neutral | N | 0.39813411 | 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.