Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17270 | 52033;52034;52035 | chr2:178609502;178609501;178609500 | chr2:179474229;179474228;179474227 |
| N2AB | 15629 | 47110;47111;47112 | chr2:178609502;178609501;178609500 | chr2:179474229;179474228;179474227 |
| N2A | 14702 | 44329;44330;44331 | chr2:178609502;178609501;178609500 | chr2:179474229;179474228;179474227 |
| N2B | 8205 | 24838;24839;24840 | chr2:178609502;178609501;178609500 | chr2:179474229;179474228;179474227 |
| Novex-1 | 8330 | 25213;25214;25215 | chr2:178609502;178609501;178609500 | chr2:179474229;179474228;179474227 |
| Novex-2 | 8397 | 25414;25415;25416 | chr2:178609502;178609501;178609500 | chr2:179474229;179474228;179474227 |
| 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 | rs200650668  |
-0.081 | None | N | 0.418 | 0.095 | None | gnomAD-2.1.1 | 4.0884E-04 | None | None | None | None | N | None | 1.24141E-04 | 1.13366E-04 | None | 0 | 0 | None | 0 | None | 0 | 8.33766E-04 | 1.40964E-04 |
| S/I | rs200650668 |
-0.081 | None | N | 0.418 | 0.095 | None | gnomAD-3.1.2 | 4.54198E-04 | None | None | None | None | N | None | 1.44907E-04 | 6.57E-05 | 0 | 0 | 0 | None | 0 | 0 | 8.9801E-04 | 0 | 4.78469E-04 |
| S/I | rs200650668 |
-0.081 | None | N | 0.418 | 0.095 | None | gnomAD-4.0.0 | 8.09272E-04 | None | None | None | None | N | None | 1.33451E-04 | 1.00127E-04 | None | 0 | 0 | None | 1.56299E-05 | 0 | 1.07026E-03 | 0 | 4.16627E-04 |
| S/R | rs2055789793 |
None | 0.007 | N | 0.605 | 0.062 | 0.271763555656 | gnomAD-4.0.0 | 1.3694E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79982E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0772 | likely_benign | 0.0783 | benign | -0.42 | Destabilizing | 0.002 | N | 0.407 | neutral | None | None | None | None | N |
| S/C | 0.0836 | likely_benign | 0.0802 | benign | -0.377 | Destabilizing | 0.196 | N | 0.623 | neutral | N | 0.48242008 | None | None | N |
| S/D | 0.2942 | likely_benign | 0.2566 | benign | 0.347 | Stabilizing | 0.004 | N | 0.422 | neutral | None | None | None | None | N |
| S/E | 0.3606 | ambiguous | 0.3176 | benign | 0.277 | Stabilizing | 0.004 | N | 0.424 | neutral | None | None | None | None | N |
| S/F | 0.1086 | likely_benign | 0.1247 | benign | -0.863 | Destabilizing | None | N | 0.429 | neutral | None | None | None | None | N |
| S/G | 0.1138 | likely_benign | 0.1098 | benign | -0.572 | Destabilizing | 0.003 | N | 0.432 | neutral | N | 0.471125651 | None | None | N |
| S/H | 0.1549 | likely_benign | 0.1346 | benign | -1.038 | Destabilizing | None | N | 0.365 | neutral | None | None | None | None | N |
| S/I | 0.0914 | likely_benign | 0.0933 | benign | -0.147 | Destabilizing | None | N | 0.418 | neutral | N | 0.438802589 | None | None | N |
| S/K | 0.389 | ambiguous | 0.3358 | benign | -0.433 | Destabilizing | 0.004 | N | 0.425 | neutral | None | None | None | None | N |
| S/L | 0.0867 | likely_benign | 0.0983 | benign | -0.147 | Destabilizing | 0.001 | N | 0.585 | neutral | None | None | None | None | N |
| S/M | 0.128 | likely_benign | 0.1294 | benign | -0.012 | Destabilizing | 0.138 | N | 0.674 | neutral | None | None | None | None | N |
| S/N | 0.0848 | likely_benign | 0.0749 | benign | -0.217 | Destabilizing | None | N | 0.132 | neutral | N | 0.436146286 | None | None | N |
| S/P | 0.6348 | likely_pathogenic | 0.6455 | pathogenic | -0.207 | Destabilizing | 0.085 | N | 0.636 | neutral | None | None | None | None | N |
| S/Q | 0.2893 | likely_benign | 0.2525 | benign | -0.434 | Destabilizing | None | N | 0.251 | neutral | None | None | None | None | N |
| S/R | 0.3199 | likely_benign | 0.2836 | benign | -0.275 | Destabilizing | 0.007 | N | 0.605 | neutral | N | 0.44701664 | None | None | N |
| S/T | 0.0655 | likely_benign | 0.0653 | benign | -0.336 | Destabilizing | None | N | 0.145 | neutral | N | 0.418347172 | None | None | N |
| S/V | 0.1041 | likely_benign | 0.102 | benign | -0.207 | Destabilizing | 0.001 | N | 0.581 | neutral | None | None | None | None | N |
| S/W | 0.227 | likely_benign | 0.2496 | benign | -0.836 | Destabilizing | 0.497 | N | 0.677 | prob.neutral | None | None | None | None | N |
| S/Y | 0.0963 | likely_benign | 0.0982 | benign | -0.56 | Destabilizing | 0.009 | N | 0.628 | 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.