Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26904 | 80935;80936;80937 | chr2:178565422;178565421;178565420 | chr2:179430149;179430148;179430147 |
| N2AB | 25263 | 76012;76013;76014 | chr2:178565422;178565421;178565420 | chr2:179430149;179430148;179430147 |
| N2A | 24336 | 73231;73232;73233 | chr2:178565422;178565421;178565420 | chr2:179430149;179430148;179430147 |
| N2B | 17839 | 53740;53741;53742 | chr2:178565422;178565421;178565420 | chr2:179430149;179430148;179430147 |
| Novex-1 | 17964 | 54115;54116;54117 | chr2:178565422;178565421;178565420 | chr2:179430149;179430148;179430147 |
| Novex-2 | 18031 | 54316;54317;54318 | chr2:178565422;178565421;178565420 | chr2:179430149;179430148;179430147 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | rs773395582  |
-0.251 | 0.81 | N | 0.351 | 0.134 | 0.531873083431 | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 4.44E-05 | 0 |
| I/M | rs773395582 |
-0.251 | 0.81 | N | 0.351 | 0.134 | 0.531873083431 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| I/M | rs773395582 |
-0.251 | 0.81 | N | 0.351 | 0.134 | 0.531873083431 | gnomAD-4.0.0 | 3.65691E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.00149E-05 | 0 | 0 |
| I/T | rs991499250 |
None | 0.549 | N | 0.26 | 0.257 | 0.638307893888 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs991499250 |
None | 0.549 | N | 0.26 | 0.257 | 0.638307893888 | gnomAD-4.0.0 | 6.57367E-06 | None | None | None | None | I | None | 0 | 6.55652E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.1345 | likely_benign | 0.1254 | benign | -0.678 | Destabilizing | 0.4 | N | 0.271 | neutral | None | None | None | None | I |
| I/C | 0.5912 | likely_pathogenic | 0.5814 | pathogenic | -0.712 | Destabilizing | 0.992 | D | 0.294 | neutral | None | None | None | None | I |
| I/D | 0.5653 | likely_pathogenic | 0.563 | ambiguous | -0.009 | Destabilizing | 0.92 | D | 0.371 | neutral | None | None | None | None | I |
| I/E | 0.408 | ambiguous | 0.4221 | ambiguous | -0.065 | Destabilizing | 0.617 | D | 0.355 | neutral | None | None | None | None | I |
| I/F | 0.1082 | likely_benign | 0.1126 | benign | -0.48 | Destabilizing | 0.002 | N | 0.109 | neutral | None | None | None | None | I |
| I/G | 0.4825 | ambiguous | 0.4486 | ambiguous | -0.883 | Destabilizing | 0.766 | D | 0.356 | neutral | None | None | None | None | I |
| I/H | 0.3505 | ambiguous | 0.3411 | ambiguous | -0.082 | Destabilizing | 0.992 | D | 0.329 | neutral | None | None | None | None | I |
| I/K | 0.2569 | likely_benign | 0.2669 | benign | -0.409 | Destabilizing | 0.016 | N | 0.248 | neutral | N | 0.406650098 | None | None | I |
| I/L | 0.1002 | likely_benign | 0.0909 | benign | -0.245 | Destabilizing | 0.002 | N | 0.122 | neutral | N | 0.477608906 | None | None | I |
| I/M | 0.0782 | likely_benign | 0.0732 | benign | -0.435 | Destabilizing | 0.81 | D | 0.351 | neutral | N | 0.516031221 | None | None | I |
| I/N | 0.2227 | likely_benign | 0.2122 | benign | -0.259 | Destabilizing | 0.92 | D | 0.367 | neutral | None | None | None | None | I |
| I/P | 0.7902 | likely_pathogenic | 0.7664 | pathogenic | -0.356 | Destabilizing | 0.972 | D | 0.369 | neutral | None | None | None | None | I |
| I/Q | 0.3029 | likely_benign | 0.2994 | benign | -0.416 | Destabilizing | 0.85 | D | 0.366 | neutral | None | None | None | None | I |
| I/R | 0.1748 | likely_benign | 0.1842 | benign | 0.092 | Stabilizing | 0.681 | D | 0.37 | neutral | N | 0.41909932 | None | None | I |
| I/S | 0.1481 | likely_benign | 0.1385 | benign | -0.778 | Destabilizing | 0.617 | D | 0.294 | neutral | None | None | None | None | I |
| I/T | 0.0703 | likely_benign | 0.0657 | benign | -0.718 | Destabilizing | 0.549 | D | 0.26 | neutral | N | 0.441224032 | None | None | I |
| I/V | 0.0794 | likely_benign | 0.0766 | benign | -0.356 | Destabilizing | 0.099 | N | 0.169 | neutral | N | 0.44645928 | None | None | I |
| I/W | 0.5932 | likely_pathogenic | 0.5878 | pathogenic | -0.506 | Destabilizing | 0.992 | D | 0.341 | neutral | None | None | None | None | I |
| I/Y | 0.3746 | ambiguous | 0.3963 | ambiguous | -0.268 | Destabilizing | 0.447 | N | 0.328 | neutral | 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.