Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24726 | 74401;74402;74403 | chr2:178571956;178571955;178571954 | chr2:179436683;179436682;179436681 |
| N2AB | 23085 | 69478;69479;69480 | chr2:178571956;178571955;178571954 | chr2:179436683;179436682;179436681 |
| N2A | 22158 | 66697;66698;66699 | chr2:178571956;178571955;178571954 | chr2:179436683;179436682;179436681 |
| N2B | 15661 | 47206;47207;47208 | chr2:178571956;178571955;178571954 | chr2:179436683;179436682;179436681 |
| Novex-1 | 15786 | 47581;47582;47583 | chr2:178571956;178571955;178571954 | chr2:179436683;179436682;179436681 |
| Novex-2 | 15853 | 47782;47783;47784 | chr2:178571956;178571955;178571954 | chr2:179436683;179436682;179436681 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs1559408209  |
None | 0.267 | N | 0.207 | 0.253 | 0.366659145958 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 6.47E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/A | rs1559408209 |
None | 0.267 | N | 0.207 | 0.253 | 0.366659145958 | gnomAD-4.0.0 | 4.1065E-06 | None | None | None | None | N | None | 2.98989E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 4.49798E-06 | 0 | 0 |
| T/I | rs975263285 |
None | 0.966 | N | 0.382 | 0.355 | 0.556105722742 | gnomAD-4.0.0 | 9.58161E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.25942E-05 | 0 | 0 |
| T/S | None | None | 0.007 | N | 0.097 | 0.218 | 0.292423486923 | gnomAD-4.0.0 | 6.84417E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99596E-07 | 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 | 0.1085 | likely_benign | 0.108 | benign | -0.397 | Destabilizing | 0.267 | N | 0.207 | neutral | N | 0.484958768 | None | None | N |
| T/C | 0.4171 | ambiguous | 0.3855 | ambiguous | -0.401 | Destabilizing | 0.998 | D | 0.393 | neutral | None | None | None | None | N |
| T/D | 0.7726 | likely_pathogenic | 0.7764 | pathogenic | 0.527 | Stabilizing | 0.842 | D | 0.351 | neutral | None | None | None | None | N |
| T/E | 0.698 | likely_pathogenic | 0.7237 | pathogenic | 0.544 | Stabilizing | 0.842 | D | 0.346 | neutral | None | None | None | None | N |
| T/F | 0.4247 | ambiguous | 0.4239 | ambiguous | -0.632 | Destabilizing | 0.991 | D | 0.437 | neutral | None | None | None | None | N |
| T/G | 0.3847 | ambiguous | 0.3624 | ambiguous | -0.623 | Destabilizing | 0.525 | D | 0.341 | neutral | None | None | None | None | N |
| T/H | 0.3397 | likely_benign | 0.335 | benign | -0.715 | Destabilizing | 0.991 | D | 0.415 | neutral | None | None | None | None | N |
| T/I | 0.3448 | ambiguous | 0.3643 | ambiguous | 0.102 | Stabilizing | 0.966 | D | 0.382 | neutral | N | 0.497773535 | None | None | N |
| T/K | 0.6157 | likely_pathogenic | 0.6492 | pathogenic | -0.15 | Destabilizing | 0.842 | D | 0.349 | neutral | None | None | None | None | N |
| T/L | 0.1764 | likely_benign | 0.1774 | benign | 0.102 | Stabilizing | 0.842 | D | 0.351 | neutral | None | None | None | None | N |
| T/M | 0.1274 | likely_benign | 0.1332 | benign | -0.097 | Destabilizing | 0.991 | D | 0.394 | neutral | None | None | None | None | N |
| T/N | 0.1789 | likely_benign | 0.1687 | benign | -0.268 | Destabilizing | 0.801 | D | 0.273 | neutral | N | 0.511164119 | None | None | N |
| T/P | 0.3405 | ambiguous | 0.316 | benign | -0.032 | Destabilizing | 0.891 | D | 0.389 | neutral | N | 0.512181284 | None | None | N |
| T/Q | 0.4515 | ambiguous | 0.46 | ambiguous | -0.285 | Destabilizing | 0.974 | D | 0.395 | neutral | None | None | None | None | N |
| T/R | 0.5102 | ambiguous | 0.5405 | ambiguous | -0.021 | Destabilizing | 0.949 | D | 0.377 | neutral | None | None | None | None | N |
| T/S | 0.0967 | likely_benign | 0.092 | benign | -0.563 | Destabilizing | 0.007 | N | 0.097 | neutral | N | 0.438013155 | None | None | N |
| T/V | 0.2321 | likely_benign | 0.2399 | benign | -0.032 | Destabilizing | 0.842 | D | 0.27 | neutral | None | None | None | None | N |
| T/W | 0.729 | likely_pathogenic | 0.7107 | pathogenic | -0.677 | Destabilizing | 0.998 | D | 0.491 | neutral | None | None | None | None | N |
| T/Y | 0.3483 | ambiguous | 0.3392 | benign | -0.342 | Destabilizing | 0.991 | D | 0.432 | neutral | 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.