Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23852 | 71779;71780;71781 | chr2:178574578;178574577;178574576 | chr2:179439305;179439304;179439303 |
| N2AB | 22211 | 66856;66857;66858 | chr2:178574578;178574577;178574576 | chr2:179439305;179439304;179439303 |
| N2A | 21284 | 64075;64076;64077 | chr2:178574578;178574577;178574576 | chr2:179439305;179439304;179439303 |
| N2B | 14787 | 44584;44585;44586 | chr2:178574578;178574577;178574576 | chr2:179439305;179439304;179439303 |
| Novex-1 | 14912 | 44959;44960;44961 | chr2:178574578;178574577;178574576 | chr2:179439305;179439304;179439303 |
| Novex-2 | 14979 | 45160;45161;45162 | chr2:178574578;178574577;178574576 | chr2:179439305;179439304;179439303 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/C | rs1177699712  |
-0.278 | 0.928 | N | 0.366 | 0.3 | 0.350964488264 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| S/C | rs1177699712 |
-0.278 | 0.928 | N | 0.366 | 0.3 | 0.350964488264 | gnomAD-4.0.0 | 1.64235E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.15901E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0982 | likely_benign | 0.0962 | benign | -0.24 | Destabilizing | 0.09 | N | 0.369 | neutral | N | 0.502181198 | None | None | I |
| S/C | 0.1145 | likely_benign | 0.1135 | benign | -0.248 | Destabilizing | 0.928 | D | 0.366 | neutral | N | 0.484215893 | None | None | I |
| S/D | 0.3651 | ambiguous | 0.3591 | ambiguous | 0.226 | Stabilizing | 0.241 | N | 0.295 | neutral | None | None | None | None | I |
| S/E | 0.5409 | ambiguous | 0.546 | ambiguous | 0.127 | Stabilizing | 0.388 | N | 0.325 | neutral | None | None | None | None | I |
| S/F | 0.1798 | likely_benign | 0.1818 | benign | -0.902 | Destabilizing | 0.773 | D | 0.488 | neutral | N | 0.483768795 | None | None | I |
| S/G | 0.1165 | likely_benign | 0.1088 | benign | -0.328 | Destabilizing | 0.116 | N | 0.302 | neutral | None | None | None | None | I |
| S/H | 0.2968 | likely_benign | 0.305 | benign | -0.807 | Destabilizing | 0.818 | D | 0.363 | neutral | None | None | None | None | I |
| S/I | 0.172 | likely_benign | 0.1711 | benign | -0.141 | Destabilizing | 0.527 | D | 0.479 | neutral | None | None | None | None | I |
| S/K | 0.7067 | likely_pathogenic | 0.6933 | pathogenic | -0.371 | Destabilizing | 0.388 | N | 0.323 | neutral | None | None | None | None | I |
| S/L | 0.096 | likely_benign | 0.0914 | benign | -0.141 | Destabilizing | 0.241 | N | 0.452 | neutral | None | None | None | None | I |
| S/M | 0.1542 | likely_benign | 0.1466 | benign | -0.002 | Destabilizing | 0.944 | D | 0.355 | neutral | None | None | None | None | I |
| S/N | 0.1101 | likely_benign | 0.1099 | benign | -0.093 | Destabilizing | 0.001 | N | 0.076 | neutral | None | None | None | None | I |
| S/P | 0.6465 | likely_pathogenic | 0.6455 | pathogenic | -0.146 | Destabilizing | 0.773 | D | 0.4 | neutral | N | 0.518420087 | None | None | I |
| S/Q | 0.4951 | ambiguous | 0.4957 | ambiguous | -0.32 | Destabilizing | 0.818 | D | 0.371 | neutral | None | None | None | None | I |
| S/R | 0.6506 | likely_pathogenic | 0.6478 | pathogenic | -0.185 | Destabilizing | 0.69 | D | 0.405 | neutral | None | None | None | None | I |
| S/T | 0.0728 | likely_benign | 0.0691 | benign | -0.196 | Destabilizing | 0.001 | N | 0.075 | neutral | N | 0.508472452 | None | None | I |
| S/V | 0.1807 | likely_benign | 0.1777 | benign | -0.146 | Destabilizing | 0.241 | N | 0.492 | neutral | None | None | None | None | I |
| S/W | 0.3405 | ambiguous | 0.339 | benign | -0.95 | Destabilizing | 0.981 | D | 0.555 | neutral | None | None | None | None | I |
| S/Y | 0.177 | likely_benign | 0.1833 | benign | -0.643 | Destabilizing | 0.773 | D | 0.479 | neutral | N | 0.464470959 | 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.