Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17569 | 52930;52931;52932 | chr2:178608178;178608081;178608080 | chr2:179472905;179472808;179472807 |
| N2AB | 15928 | 48007;48008;48009 | chr2:178608178;178608081;178608080 | chr2:179472905;179472808;179472807 |
| N2A | 15001 | 45226;45227;45228 | chr2:178608178;178608081;178608080 | chr2:179472905;179472808;179472807 |
| N2B | 8504 | 25735;25736;25737 | chr2:178608178;178608081;178608080 | chr2:179472905;179472808;179472807 |
| Novex-1 | 8629 | 26110;26111;26112 | chr2:178608178;178608081;178608080 | chr2:179472905;179472808;179472807 |
| Novex-2 | 8696 | 26311;26312;26313 | chr2:178608178;178608081;178608080 | chr2:179472905;179472808;179472807 |
| 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/Y | rs756689649  |
-0.68 | 0.855 | N | 0.517 | None | 0.415690173769 | gnomAD-2.1.1 | 1.64E-05 | None | None | None | None | I | None | 0 | 2.93E-05 | None | 0 | 0 | None | 0 | None | 0 | 2.73E-05 | 0 |
| S/Y | rs756689649 |
-0.68 | 0.855 | N | 0.517 | None | 0.415690173769 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 4.42E-05 | 0 | 0 |
| S/Y | rs756689649 |
-0.68 | 0.855 | N | 0.517 | None | 0.415690173769 | gnomAD-4.0.0 | 9.92872E-06 | None | None | None | None | I | None | 0 | 3.34919E-05 | None | 0 | 0 | None | 0 | 0 | 1.10285E-05 | 0 | 1.60462E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0704 | likely_benign | 0.0741 | benign | -0.295 | Destabilizing | 0.13 | N | 0.161 | neutral | N | 0.410436112 | None | None | I |
| S/C | 0.086 | likely_benign | 0.0878 | benign | -0.33 | Destabilizing | 0.947 | D | 0.277 | neutral | N | 0.453934595 | None | None | I |
| S/D | 0.3101 | likely_benign | 0.3388 | benign | 0.414 | Stabilizing | 0.872 | D | 0.172 | neutral | None | None | None | None | I |
| S/E | 0.3231 | likely_benign | 0.3681 | ambiguous | 0.318 | Stabilizing | 0.691 | D | 0.171 | neutral | None | None | None | None | I |
| S/F | 0.1099 | likely_benign | 0.1119 | benign | -0.949 | Destabilizing | 0.454 | N | 0.465 | neutral | N | 0.46888977 | None | None | I |
| S/G | 0.1219 | likely_benign | 0.1248 | benign | -0.379 | Destabilizing | 0.479 | N | 0.17 | neutral | None | None | None | None | I |
| S/H | 0.2434 | likely_benign | 0.254 | benign | -0.768 | Destabilizing | 0.96 | D | 0.297 | neutral | None | None | None | None | I |
| S/I | 0.1087 | likely_benign | 0.1076 | benign | -0.208 | Destabilizing | 0.185 | N | 0.294 | neutral | None | None | None | None | I |
| S/K | 0.446 | ambiguous | 0.4687 | ambiguous | -0.321 | Destabilizing | 0.524 | D | 0.173 | neutral | None | None | None | None | I |
| S/L | 0.0544 | likely_benign | 0.0536 | benign | -0.208 | Destabilizing | None | N | 0.095 | neutral | None | None | None | None | I |
| S/M | 0.1118 | likely_benign | 0.1162 | benign | -0.121 | Destabilizing | 0.018 | N | 0.088 | neutral | None | None | None | None | I |
| S/N | 0.1425 | likely_benign | 0.1416 | benign | -0.109 | Destabilizing | 0.872 | D | 0.183 | neutral | None | None | None | None | I |
| S/P | 0.5688 | likely_pathogenic | 0.6254 | pathogenic | -0.209 | Destabilizing | 0.837 | D | 0.431 | neutral | N | 0.462617158 | None | None | I |
| S/Q | 0.306 | likely_benign | 0.3361 | benign | -0.309 | Destabilizing | 0.691 | D | 0.172 | neutral | None | None | None | None | I |
| S/R | 0.4007 | ambiguous | 0.4033 | ambiguous | -0.134 | Destabilizing | 0.691 | D | 0.438 | neutral | None | None | None | None | I |
| S/T | 0.0814 | likely_benign | 0.0767 | benign | -0.238 | Destabilizing | 0.255 | N | 0.186 | neutral | N | 0.415380572 | None | None | I |
| S/V | 0.1096 | likely_benign | 0.1145 | benign | -0.209 | Destabilizing | 0.09 | N | 0.275 | neutral | None | None | None | None | I |
| S/W | 0.2302 | likely_benign | 0.246 | benign | -0.985 | Destabilizing | 0.989 | D | 0.363 | neutral | None | None | None | None | I |
| S/Y | 0.1087 | likely_benign | 0.1109 | benign | -0.681 | Destabilizing | 0.855 | D | 0.517 | neutral | N | 0.457942057 | 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.