Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23584 | 70975;70976;70977 | chr2:178575382;178575381;178575380 | chr2:179440109;179440108;179440107 |
| N2AB | 21943 | 66052;66053;66054 | chr2:178575382;178575381;178575380 | chr2:179440109;179440108;179440107 |
| N2A | 21016 | 63271;63272;63273 | chr2:178575382;178575381;178575380 | chr2:179440109;179440108;179440107 |
| N2B | 14519 | 43780;43781;43782 | chr2:178575382;178575381;178575380 | chr2:179440109;179440108;179440107 |
| Novex-1 | 14644 | 44155;44156;44157 | chr2:178575382;178575381;178575380 | chr2:179440109;179440108;179440107 |
| Novex-2 | 14711 | 44356;44357;44358 | chr2:178575382;178575381;178575380 | chr2:179440109;179440108;179440107 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs765545404  |
-0.385 | 0.022 | N | 0.52 | 0.104 | 0.206339911435 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| T/A | rs765545404 |
-0.385 | 0.022 | N | 0.52 | 0.104 | 0.206339911435 | gnomAD-4.0.0 | 3.18344E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.86574E-05 | 0 |
| T/I | rs1444861045 |
None | 0.917 | N | 0.697 | 0.431 | 0.406257615169 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| T/I | rs1444861045 |
None | 0.917 | N | 0.697 | 0.431 | 0.406257615169 | gnomAD-4.0.0 | 6.57479E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47067E-05 | 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 | 0.1052 | likely_benign | 0.099 | benign | -0.549 | Destabilizing | 0.022 | N | 0.52 | neutral | N | 0.465631112 | None | None | I |
| T/C | 0.5689 | likely_pathogenic | 0.5426 | ambiguous | -0.366 | Destabilizing | 0.992 | D | 0.665 | neutral | None | None | None | None | I |
| T/D | 0.6137 | likely_pathogenic | 0.6256 | pathogenic | 0.184 | Stabilizing | 0.609 | D | 0.663 | neutral | None | None | None | None | I |
| T/E | 0.4619 | ambiguous | 0.47 | ambiguous | 0.162 | Stabilizing | 0.838 | D | 0.657 | neutral | None | None | None | None | I |
| T/F | 0.475 | ambiguous | 0.3935 | ambiguous | -0.691 | Destabilizing | 0.992 | D | 0.747 | deleterious | None | None | None | None | I |
| T/G | 0.4619 | ambiguous | 0.4384 | ambiguous | -0.776 | Destabilizing | 0.788 | D | 0.617 | neutral | None | None | None | None | I |
| T/H | 0.4197 | ambiguous | 0.3967 | ambiguous | -0.974 | Destabilizing | 0.994 | D | 0.739 | prob.delet. | None | None | None | None | I |
| T/I | 0.2378 | likely_benign | 0.1764 | benign | -0.051 | Destabilizing | 0.917 | D | 0.697 | prob.neutral | N | 0.478531127 | None | None | I |
| T/K | 0.4208 | ambiguous | 0.4217 | ambiguous | -0.543 | Destabilizing | 0.879 | D | 0.673 | neutral | None | None | None | None | I |
| T/L | 0.163 | likely_benign | 0.1295 | benign | -0.051 | Destabilizing | 0.674 | D | 0.656 | neutral | None | None | None | None | I |
| T/M | 0.1159 | likely_benign | 0.1012 | benign | 0.068 | Stabilizing | 0.994 | D | 0.668 | neutral | None | None | None | None | I |
| T/N | 0.2068 | likely_benign | 0.1974 | benign | -0.415 | Destabilizing | 0.54 | D | 0.621 | neutral | N | 0.519788311 | None | None | I |
| T/P | 0.3738 | ambiguous | 0.3617 | ambiguous | -0.185 | Destabilizing | 0.001 | N | 0.397 | neutral | N | 0.504397571 | None | None | I |
| T/Q | 0.3474 | ambiguous | 0.3442 | ambiguous | -0.566 | Destabilizing | 0.873 | D | 0.697 | prob.neutral | None | None | None | None | I |
| T/R | 0.3639 | ambiguous | 0.3589 | ambiguous | -0.292 | Destabilizing | 0.975 | D | 0.7 | prob.neutral | None | None | None | None | I |
| T/S | 0.1661 | likely_benign | 0.1623 | benign | -0.704 | Destabilizing | 0.004 | N | 0.355 | neutral | N | 0.505859008 | None | None | I |
| T/V | 0.133 | likely_benign | 0.1112 | benign | -0.185 | Destabilizing | 0.596 | D | 0.584 | neutral | None | None | None | None | I |
| T/W | 0.8004 | likely_pathogenic | 0.7695 | pathogenic | -0.653 | Destabilizing | 0.998 | D | 0.763 | deleterious | None | None | None | None | I |
| T/Y | 0.4913 | ambiguous | 0.4412 | ambiguous | -0.407 | Destabilizing | 0.992 | D | 0.749 | deleterious | None | None | 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.