Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19832 | 59719;59720;59721 | chr2:178592511;178592510;178592509 | chr2:179457238;179457237;179457236 |
| N2AB | 18191 | 54796;54797;54798 | chr2:178592511;178592510;178592509 | chr2:179457238;179457237;179457236 |
| N2A | 17264 | 52015;52016;52017 | chr2:178592511;178592510;178592509 | chr2:179457238;179457237;179457236 |
| N2B | 10767 | 32524;32525;32526 | chr2:178592511;178592510;178592509 | chr2:179457238;179457237;179457236 |
| Novex-1 | 10892 | 32899;32900;32901 | chr2:178592511;178592510;178592509 | chr2:179457238;179457237;179457236 |
| Novex-2 | 10959 | 33100;33101;33102 | chr2:178592511;178592510;178592509 | chr2:179457238;179457237;179457236 |
| 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/I | rs1405596883  |
None | 0.029 | N | 0.493 | 0.141 | 0.365509141856 | gnomAD-4.0.0 | 3.18366E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.88253E-05 | 0 | 2.8594E-06 | 0 | 0 |
| R/K | rs1405596883 |
-0.781 | 0.005 | N | 0.16 | 0.085 | 0.112648838833 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| R/K | rs1405596883 |
-0.781 | 0.005 | N | 0.16 | 0.085 | 0.112648838833 | gnomAD-4.0.0 | 1.59183E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8594E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.1595 | likely_benign | 0.1727 | benign | -0.344 | Destabilizing | 0.007 | N | 0.234 | neutral | None | None | None | None | N |
| R/C | 0.1149 | likely_benign | 0.1017 | benign | -0.273 | Destabilizing | 0.676 | D | 0.379 | neutral | None | None | None | None | N |
| R/D | 0.2316 | likely_benign | 0.266 | benign | 0.094 | Stabilizing | None | N | 0.146 | neutral | None | None | None | None | N |
| R/E | 0.1545 | likely_benign | 0.1747 | benign | 0.209 | Stabilizing | None | N | 0.093 | neutral | None | None | None | None | N |
| R/F | 0.2885 | likely_benign | 0.2639 | benign | -0.227 | Destabilizing | 0.356 | N | 0.455 | neutral | None | None | None | None | N |
| R/G | 0.1534 | likely_benign | 0.1569 | benign | -0.642 | Destabilizing | 0.024 | N | 0.231 | neutral | N | 0.496252516 | None | None | N |
| R/H | 0.072 | likely_benign | 0.0695 | benign | -1.093 | Destabilizing | 0.214 | N | 0.229 | neutral | None | None | None | None | N |
| R/I | 0.117 | likely_benign | 0.1122 | benign | 0.443 | Stabilizing | 0.029 | N | 0.493 | neutral | N | 0.502602485 | None | None | N |
| R/K | 0.075 | likely_benign | 0.0745 | benign | -0.359 | Destabilizing | 0.005 | N | 0.16 | neutral | N | 0.477106608 | None | None | N |
| R/L | 0.1237 | likely_benign | 0.1223 | benign | 0.443 | Stabilizing | 0.016 | N | 0.287 | neutral | None | None | None | None | N |
| R/M | 0.1485 | likely_benign | 0.1387 | benign | 0.021 | Stabilizing | 0.356 | N | 0.319 | neutral | None | None | None | None | N |
| R/N | 0.1884 | likely_benign | 0.202 | benign | 0.11 | Stabilizing | 0.016 | N | 0.174 | neutral | None | None | None | None | N |
| R/P | 0.6773 | likely_pathogenic | 0.7504 | pathogenic | 0.203 | Stabilizing | 0.136 | N | 0.316 | neutral | None | None | None | None | N |
| R/Q | 0.0656 | likely_benign | 0.0687 | benign | -0.009 | Destabilizing | None | N | 0.109 | neutral | None | None | None | None | N |
| R/S | 0.1762 | likely_benign | 0.1908 | benign | -0.492 | Destabilizing | 0.005 | N | 0.282 | neutral | N | 0.475954602 | None | None | N |
| R/T | 0.099 | likely_benign | 0.1031 | benign | -0.201 | Destabilizing | None | N | 0.171 | neutral | N | 0.481880496 | None | None | N |
| R/V | 0.127 | likely_benign | 0.1347 | benign | 0.203 | Stabilizing | 0.016 | N | 0.325 | neutral | None | None | None | None | N |
| R/W | 0.1355 | likely_benign | 0.1249 | benign | -0.018 | Destabilizing | 0.864 | D | 0.385 | neutral | None | None | None | None | N |
| R/Y | 0.2102 | likely_benign | 0.1976 | benign | 0.313 | Stabilizing | 0.356 | N | 0.43 | 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.