Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 66 | 421;422;423 | chr2:178802237;178802236;178802235 | chr2:179666964;179666963;179666962 |
| N2AB | 66 | 421;422;423 | chr2:178802237;178802236;178802235 | chr2:179666964;179666963;179666962 |
| N2A | 66 | 421;422;423 | chr2:178802237;178802236;178802235 | chr2:179666964;179666963;179666962 |
| N2B | 66 | 421;422;423 | chr2:178802237;178802236;178802235 | chr2:179666964;179666963;179666962 |
| Novex-1 | 66 | 421;422;423 | chr2:178802237;178802236;178802235 | chr2:179666964;179666963;179666962 |
| Novex-2 | 66 | 421;422;423 | chr2:178802237;178802236;178802235 | chr2:179666964;179666963;179666962 |
| Novex-3 | 66 | 421;422;423 | chr2:178802237;178802236;178802235 | chr2:179666964;179666963;179666962 |
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/M | rs372755739  |
-0.086 | 0.014 | D | 0.383 | 0.124 | None | gnomAD-2.1.1 | 4.24E-05 | None | None | None | 0.005(TCAP) | N | None | 0 | 0 | None | 9.65E-05 | 0 | None | 9.8E-05 | None | 1.19408E-04 | 3.87E-05 | 0 |
| T/M | rs372755739 |
-0.086 | 0.014 | D | 0.383 | 0.124 | None | gnomAD-3.1.2 | 3.94E-05 | None | None | None | 0.005(TCAP) | N | None | 0 | 0 | 0 | 0 | 0 | None | 9.42E-05 | 0 | 7.35E-05 | 0 | 0 |
| T/M | rs372755739 |
-0.086 | 0.014 | D | 0.383 | 0.124 | None | gnomAD-4.0.0 | 4.58489E-05 | None | None | None | 0.005(TCAP) | N | None | 0 | 0 | None | 3.37769E-05 | 0 | None | 1.09327E-04 | 0 | 4.74569E-05 | 9.88056E-05 | 1.60041E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1209 | likely_benign | 0.1217 | benign | -1.006 | Destabilizing | 0.003 | N | 0.513 | neutral | D | 0.557084038 | None | -0.012(TCAP) | N |
| T/C | 0.7342 | likely_pathogenic | 0.6964 | pathogenic | -0.891 | Destabilizing | 0.76 | D | 0.612 | neutral | None | None | None | -0.726(TCAP) | N |
| T/D | 0.4741 | ambiguous | 0.5047 | ambiguous | -1.229 | Destabilizing | 0.114 | N | 0.625 | neutral | None | None | None | -0.489(TCAP) | N |
| T/E | 0.2798 | likely_benign | 0.2985 | benign | -1.121 | Destabilizing | 0.081 | N | 0.557 | neutral | None | None | None | -0.629(TCAP) | N |
| T/F | 0.2474 | likely_benign | 0.2434 | benign | -0.725 | Destabilizing | 0.849 | D | 0.653 | neutral | None | None | None | -0.191(TCAP) | N |
| T/G | 0.422 | ambiguous | 0.435 | ambiguous | -1.361 | Destabilizing | 0.307 | N | 0.577 | neutral | None | None | None | 0.042(TCAP) | N |
| T/H | 0.293 | likely_benign | 0.2953 | benign | -1.584 | Destabilizing | 0.81 | D | 0.593 | neutral | None | None | None | 0.305(TCAP) | N |
| T/I | 0.115 | likely_benign | 0.119 | benign | -0.112 | Destabilizing | 0.041 | N | 0.525 | neutral | None | None | None | -0.247(TCAP) | N |
| T/K | 0.2389 | likely_benign | 0.242 | benign | -0.921 | Destabilizing | 0.002 | N | 0.384 | neutral | N | 0.516507466 | None | -1.247(TCAP) | N |
| T/L | 0.0904 | likely_benign | 0.0907 | benign | -0.112 | Destabilizing | 0.018 | N | 0.475 | neutral | None | None | None | -0.247(TCAP) | N |
| T/M | 0.0744 | likely_benign | 0.0718 | benign | -0.03 | Destabilizing | 0.014 | N | 0.383 | neutral | D | 0.551557329 | None | 0.005(TCAP) | N |
| T/N | 0.1761 | likely_benign | 0.1796 | benign | -1.257 | Destabilizing | 0.114 | N | 0.59 | neutral | None | None | None | -0.867(TCAP) | N |
| T/P | 0.8769 | likely_pathogenic | 0.8462 | pathogenic | -0.377 | Destabilizing | 0.164 | N | 0.635 | neutral | D | 0.642148367 | None | -0.158(TCAP) | N |
| T/Q | 0.194 | likely_benign | 0.2 | benign | -1.244 | Destabilizing | 0.123 | N | 0.629 | neutral | None | None | None | -0.84(TCAP) | N |
| T/R | 0.1769 | likely_benign | 0.178 | benign | -0.873 | Destabilizing | 0.004 | N | 0.369 | neutral | N | 0.476849636 | None | -1.182(TCAP) | N |
| T/S | 0.1352 | likely_benign | 0.1438 | benign | -1.459 | Destabilizing | 0.006 | N | 0.507 | neutral | N | 0.518285091 | None | -0.758(TCAP) | N |
| T/V | 0.0933 | likely_benign | 0.0978 | benign | -0.377 | Destabilizing | None | N | 0.303 | neutral | None | None | None | -0.158(TCAP) | N |
| T/W | 0.605 | likely_pathogenic | 0.5944 | pathogenic | -0.778 | Destabilizing | 0.992 | D | 0.617 | neutral | None | None | None | -0.31(TCAP) | N |
| T/Y | 0.3737 | ambiguous | 0.3657 | ambiguous | -0.481 | Destabilizing | 0.919 | D | 0.635 | neutral | None | None | None | -0.029(TCAP) | 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.