Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24 | 295;296;297 | chr2:178804573;178804572;178804571 | chr2:179669300;179669299;179669298 |
| N2AB | 24 | 295;296;297 | chr2:178804573;178804572;178804571 | chr2:179669300;179669299;179669298 |
| N2A | 24 | 295;296;297 | chr2:178804573;178804572;178804571 | chr2:179669300;179669299;179669298 |
| N2B | 24 | 295;296;297 | chr2:178804573;178804572;178804571 | chr2:179669300;179669299;179669298 |
| Novex-1 | 24 | 295;296;297 | chr2:178804573;178804572;178804571 | chr2:179669300;179669299;179669298 |
| Novex-2 | 24 | 295;296;297 | chr2:178804573;178804572;178804571 | chr2:179669300;179669299;179669298 |
| Novex-3 | 24 | 295;296;297 | chr2:178804573;178804572;178804571 | chr2:179669300;179669299;179669298 |
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/I | rs536235994  |
0.134 | 1.0 | N | 0.793 | 0.477 | 0.582733548269 | gnomAD-2.1.1 | 7.97E-06 | None | None | None | -0.166(TCAP) | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 8.81E-06 | 0 |
| T/I | rs536235994 |
0.134 | 1.0 | N | 0.793 | 0.477 | 0.582733548269 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | -0.166(TCAP) | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| T/I | rs536235994 |
0.134 | 1.0 | N | 0.793 | 0.477 | 0.582733548269 | gnomAD-4.0.0 | 4.33741E-06 | None | None | None | -0.166(TCAP) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.08487E-06 | 1.09844E-05 | 0 |
| T/N | None | -0.249 | 0.999 | N | 0.742 | 0.386 | 0.568214726415 | gnomAD-2.1.1 | 1.59E-05 | None | None | None | -0.757(TCAP) | N | None | 0 | 2.89E-05 | None | 0 | 5.45E-05 | None | 0 | None | 0 | 8.81E-06 | 1.63239E-04 |
| T/N | None | -0.249 | 0.999 | N | 0.742 | 0.386 | 0.568214726415 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | -0.757(TCAP) | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 2.07125E-04 | 0 |
| T/N | None | -0.249 | 0.999 | N | 0.742 | 0.386 | 0.568214726415 | gnomAD-4.0.0 | 1.05337E-05 | None | None | None | -0.757(TCAP) | N | None | 0 | 1.66678E-05 | None | 0 | 0 | None | 0 | 1.64366E-04 | 1.01697E-05 | 2.19688E-05 | 1.60067E-05 |
| T/P | rs758953324 |
-0.384 | 0.999 | D | 0.791 | 0.448 | 0.599805095821 | gnomAD-2.1.1 | 1.19E-05 | None | None | None | -0.15(TCAP) | N | None | 0 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 0 | 1.63292E-04 |
| T/P | rs758953324 |
-0.384 | 0.999 | D | 0.791 | 0.448 | 0.599805095821 | gnomAD-4.0.0 | 6.15713E-06 | None | None | None | -0.15(TCAP) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.04394E-04 | 0 |
| T/S | rs536235994 |
-0.632 | 0.993 | N | 0.597 | 0.25 | 0.389750110748 | gnomAD-2.1.1 | 7.97E-06 | None | None | None | -0.641(TCAP) | N | None | 0 | 5.79E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/S | rs536235994 |
-0.632 | 0.993 | N | 0.597 | 0.25 | 0.389750110748 | gnomAD-4.0.0 | 1.16301E-05 | None | None | None | -0.641(TCAP) | N | None | 5.97372E-05 | 8.94494E-05 | None | 0 | 0 | None | 0 | 0 | 9.8926E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0917 | likely_benign | 0.0906 | benign | -0.875 | Destabilizing | 0.993 | D | 0.617 | neutral | N | 0.457650797 | None | -0.135(TCAP) | N |
| T/C | 0.6948 | likely_pathogenic | 0.7021 | pathogenic | -0.539 | Destabilizing | 1.0 | D | 0.774 | deleterious | None | None | None | -0.254(TCAP) | N |
| T/D | 0.4164 | ambiguous | 0.4171 | ambiguous | -0.012 | Destabilizing | 0.999 | D | 0.797 | deleterious | None | None | None | -0.302(TCAP) | N |
| T/E | 0.3238 | likely_benign | 0.3235 | benign | 0.038 | Stabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | -0.371(TCAP) | N |
| T/F | 0.2999 | likely_benign | 0.3075 | benign | -0.872 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | -0.033(TCAP) | N |
| T/G | 0.3336 | likely_benign | 0.3364 | benign | -1.171 | Destabilizing | 1.0 | D | 0.744 | deleterious | None | None | None | -0.134(TCAP) | N |
| T/H | 0.3254 | likely_benign | 0.3347 | benign | -1.26 | Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | 0.445(TCAP) | N |
| T/I | 0.1442 | likely_benign | 0.1455 | benign | -0.164 | Destabilizing | 1.0 | D | 0.793 | deleterious | N | 0.453953636 | None | -0.166(TCAP) | N |
| T/K | 0.2789 | likely_benign | 0.2882 | benign | -0.561 | Destabilizing | 1.0 | D | 0.798 | deleterious | None | None | None | -0.59(TCAP) | N |
| T/L | 0.1274 | likely_benign | 0.1264 | benign | -0.164 | Destabilizing | 1.0 | D | 0.684 | prob.neutral | None | None | None | -0.166(TCAP) | N |
| T/M | 0.1155 | likely_benign | 0.1157 | benign | -0.096 | Destabilizing | 1.0 | D | 0.776 | deleterious | None | None | None | 0.279(TCAP) | N |
| T/N | 0.1564 | likely_benign | 0.1488 | benign | -0.66 | Destabilizing | 0.999 | D | 0.742 | deleterious | N | 0.444872161 | None | -0.757(TCAP) | N |
| T/P | 0.4755 | ambiguous | 0.4161 | ambiguous | -0.368 | Destabilizing | 0.999 | D | 0.791 | deleterious | D | 0.606289352 | None | -0.15(TCAP) | N |
| T/Q | 0.2471 | likely_benign | 0.2525 | benign | -0.677 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | -0.601(TCAP) | N |
| T/R | 0.2105 | likely_benign | 0.2189 | benign | -0.415 | Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | -0.483(TCAP) | N |
| T/S | 0.1114 | likely_benign | 0.1101 | benign | -0.998 | Destabilizing | 0.993 | D | 0.597 | neutral | N | 0.460072036 | None | -0.641(TCAP) | N |
| T/V | 0.1158 | likely_benign | 0.121 | benign | -0.368 | Destabilizing | 0.999 | D | 0.623 | neutral | None | None | None | -0.15(TCAP) | N |
| T/W | 0.6887 | likely_pathogenic | 0.7134 | pathogenic | -0.844 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | 0.019(TCAP) | N |
| T/Y | 0.3933 | ambiguous | 0.4027 | ambiguous | -0.577 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | 0.137(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.