Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35504 | 106735;106736;106737 | chr2:178529981;178529980;178529979 | chr2:179394708;179394707;179394706 |
| N2AB | 33863 | 101812;101813;101814 | chr2:178529981;178529980;178529979 | chr2:179394708;179394707;179394706 |
| N2A | 32936 | 99031;99032;99033 | chr2:178529981;178529980;178529979 | chr2:179394708;179394707;179394706 |
| N2B | 26439 | 79540;79541;79542 | chr2:178529981;178529980;178529979 | chr2:179394708;179394707;179394706 |
| Novex-1 | 26564 | 79915;79916;79917 | chr2:178529981;178529980;178529979 | chr2:179394708;179394707;179394706 |
| Novex-2 | 26631 | 80116;80117;80118 | chr2:178529981;178529980;178529979 | chr2:179394708;179394707;179394706 |
| 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/I | None | None | 0.857 | D | 0.689 | 0.374 | 0.774508433761 | gnomAD-4.0.0 | 6.91209E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.02156E-07 | 0 | 0 |
| S/N | None | None | 0.011 | N | 0.331 | 0.143 | 0.176091768786 | gnomAD-4.0.0 | 6.91209E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.02156E-07 | 0 | 0 |
| S/T | rs575070622  |
-0.106 | 0.458 | N | 0.497 | 0.112 | 0.221734844693 | gnomAD-2.1.1 | 6.75E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 8.05E-05 | 1.28178E-04 | 0 |
| S/T | rs575070622 |
-0.106 | 0.458 | N | 0.497 | 0.112 | 0.221734844693 | gnomAD-3.1.2 | 7.23E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 9.43E-05 | 0 | 1.46985E-04 | 0 | 0 |
| S/T | rs575070622 |
-0.106 | 0.458 | N | 0.497 | 0.112 | 0.221734844693 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| S/T | rs575070622 |
-0.106 | 0.458 | N | 0.497 | 0.112 | 0.221734844693 | gnomAD-4.0.0 | 3.43962E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.12891E-05 | 0 | 4.33496E-05 | 0 | 3.22935E-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 | 0.1122 | likely_benign | 0.1148 | benign | -0.612 | Destabilizing | 0.316 | N | 0.51 | neutral | None | None | None | None | N |
| S/C | 0.2807 | likely_benign | 0.2794 | benign | -0.303 | Destabilizing | 0.986 | D | 0.609 | neutral | D | 0.522754348 | None | None | N |
| S/D | 0.4687 | ambiguous | 0.4739 | ambiguous | 0.054 | Stabilizing | 0.359 | N | 0.507 | neutral | None | None | None | None | N |
| S/E | 0.5794 | likely_pathogenic | 0.5785 | pathogenic | -0.036 | Destabilizing | 0.528 | D | 0.499 | neutral | None | None | None | None | N |
| S/F | 0.2432 | likely_benign | 0.2541 | benign | -1.206 | Destabilizing | 0.96 | D | 0.695 | prob.neutral | None | None | None | None | N |
| S/G | 0.145 | likely_benign | 0.1527 | benign | -0.725 | Destabilizing | 0.258 | N | 0.497 | neutral | N | 0.491861756 | None | None | N |
| S/H | 0.4078 | ambiguous | 0.408 | ambiguous | -1.303 | Destabilizing | 0.888 | D | 0.631 | neutral | None | None | None | None | N |
| S/I | 0.1983 | likely_benign | 0.2125 | benign | -0.437 | Destabilizing | 0.857 | D | 0.689 | prob.neutral | D | 0.531232747 | None | None | N |
| S/K | 0.6895 | likely_pathogenic | 0.6927 | pathogenic | -0.461 | Destabilizing | 0.188 | N | 0.489 | neutral | None | None | None | None | N |
| S/L | 0.1649 | likely_benign | 0.1744 | benign | -0.437 | Destabilizing | 0.528 | D | 0.641 | neutral | None | None | None | None | N |
| S/M | 0.339 | likely_benign | 0.3548 | ambiguous | 0.023 | Stabilizing | 0.989 | D | 0.617 | neutral | None | None | None | None | N |
| S/N | 0.1647 | likely_benign | 0.1743 | benign | -0.184 | Destabilizing | 0.011 | N | 0.331 | neutral | N | 0.459967295 | None | None | N |
| S/P | 0.6841 | likely_pathogenic | 0.7032 | pathogenic | -0.468 | Destabilizing | 0.96 | D | 0.616 | neutral | None | None | None | None | N |
| S/Q | 0.5318 | ambiguous | 0.5342 | ambiguous | -0.512 | Destabilizing | 0.797 | D | 0.529 | neutral | None | None | None | None | N |
| S/R | 0.5567 | ambiguous | 0.5554 | ambiguous | -0.255 | Destabilizing | 0.003 | N | 0.379 | neutral | N | 0.5013712 | None | None | N |
| S/T | 0.0944 | likely_benign | 0.0988 | benign | -0.332 | Destabilizing | 0.458 | N | 0.497 | neutral | N | 0.475011318 | None | None | N |
| S/V | 0.2253 | likely_benign | 0.2389 | benign | -0.468 | Destabilizing | 0.888 | D | 0.669 | neutral | None | None | None | None | N |
| S/W | 0.5376 | ambiguous | 0.5481 | ambiguous | -1.141 | Destabilizing | 0.989 | D | 0.729 | prob.delet. | None | None | None | None | N |
| S/Y | 0.25 | likely_benign | 0.2551 | benign | -0.883 | Destabilizing | 0.96 | D | 0.695 | prob.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.