Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16998 | 51217;51218;51219 | chr2:178611137;178611136;178611135 | chr2:179475864;179475863;179475862 |
| N2AB | 15357 | 46294;46295;46296 | chr2:178611137;178611136;178611135 | chr2:179475864;179475863;179475862 |
| N2A | 14430 | 43513;43514;43515 | chr2:178611137;178611136;178611135 | chr2:179475864;179475863;179475862 |
| N2B | 7933 | 24022;24023;24024 | chr2:178611137;178611136;178611135 | chr2:179475864;179475863;179475862 |
| Novex-1 | 8058 | 24397;24398;24399 | chr2:178611137;178611136;178611135 | chr2:179475864;179475863;179475862 |
| Novex-2 | 8125 | 24598;24599;24600 | chr2:178611137;178611136;178611135 | chr2:179475864;179475863;179475862 |
| 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/N | rs749043514  |
-0.072 | None | N | 0.139 | 0.087 | 0.0806252709748 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 3.27E-05 | None | 4.65E-05 | 0 | 0 |
| S/N | rs749043514 |
-0.072 | None | N | 0.139 | 0.087 | 0.0806252709748 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07125E-04 | 4.78469E-04 |
| S/N | rs749043514 |
-0.072 | None | N | 0.139 | 0.087 | 0.0806252709748 | gnomAD-4.0.0 | 8.97889E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.56897E-05 | 0 | 2.39617E-06 | 5.36207E-05 | 2.84852E-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 | 0.106 | likely_benign | 0.1411 | benign | -0.182 | Destabilizing | None | N | 0.131 | neutral | None | None | None | None | N |
| S/C | 0.1504 | likely_benign | 0.1612 | benign | -0.307 | Destabilizing | 0.946 | D | 0.301 | neutral | N | 0.475645772 | None | None | N |
| S/D | 0.2625 | likely_benign | 0.3552 | ambiguous | 0.088 | Stabilizing | None | N | 0.091 | neutral | None | None | None | None | N |
| S/E | 0.518 | ambiguous | 0.6556 | pathogenic | -0.02 | Destabilizing | 0.055 | N | 0.255 | neutral | None | None | None | None | N |
| S/F | 0.3617 | ambiguous | 0.5167 | ambiguous | -0.901 | Destabilizing | 0.859 | D | 0.395 | neutral | None | None | None | None | N |
| S/G | 0.0719 | likely_benign | 0.0811 | benign | -0.242 | Destabilizing | None | N | 0.113 | neutral | N | 0.445143215 | None | None | N |
| S/H | 0.4821 | ambiguous | 0.5769 | pathogenic | -0.652 | Destabilizing | 0.497 | N | 0.317 | neutral | None | None | None | None | N |
| S/I | 0.2737 | likely_benign | 0.4205 | ambiguous | -0.16 | Destabilizing | 0.427 | N | 0.469 | neutral | N | 0.497187849 | None | None | N |
| S/K | 0.7484 | likely_pathogenic | 0.8455 | pathogenic | -0.391 | Destabilizing | 0.055 | N | 0.235 | neutral | None | None | None | None | N |
| S/L | 0.1483 | likely_benign | 0.2151 | benign | -0.16 | Destabilizing | 0.22 | N | 0.331 | neutral | None | None | None | None | N |
| S/M | 0.265 | likely_benign | 0.349 | ambiguous | -0.081 | Destabilizing | 0.859 | D | 0.305 | neutral | None | None | None | None | N |
| S/N | 0.1255 | likely_benign | 0.1731 | benign | -0.134 | Destabilizing | None | N | 0.139 | neutral | N | 0.437973066 | None | None | N |
| S/P | 0.5652 | likely_pathogenic | 0.6586 | pathogenic | -0.142 | Destabilizing | 0.364 | N | 0.433 | neutral | None | None | None | None | N |
| S/Q | 0.6248 | likely_pathogenic | 0.7193 | pathogenic | -0.364 | Destabilizing | 0.22 | N | 0.311 | neutral | None | None | None | None | N |
| S/R | 0.7156 | likely_pathogenic | 0.8131 | pathogenic | -0.169 | Destabilizing | 0.175 | N | 0.426 | neutral | N | 0.451923347 | None | None | N |
| S/T | 0.0802 | likely_benign | 0.0911 | benign | -0.234 | Destabilizing | 0.081 | N | 0.333 | neutral | N | 0.432350525 | None | None | N |
| S/V | 0.2458 | likely_benign | 0.3484 | ambiguous | -0.142 | Destabilizing | 0.124 | N | 0.392 | neutral | None | None | None | None | N |
| S/W | 0.5435 | ambiguous | 0.6409 | pathogenic | -0.976 | Destabilizing | 0.958 | D | 0.403 | neutral | None | None | None | None | N |
| S/Y | 0.3693 | ambiguous | 0.4877 | ambiguous | -0.661 | Destabilizing | 0.859 | D | 0.394 | 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.