Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29626 | 89101;89102;89103 | chr2:178554471;178554470;178554469 | chr2:179419198;179419197;179419196 |
| N2AB | 27985 | 84178;84179;84180 | chr2:178554471;178554470;178554469 | chr2:179419198;179419197;179419196 |
| N2A | 27058 | 81397;81398;81399 | chr2:178554471;178554470;178554469 | chr2:179419198;179419197;179419196 |
| N2B | 20561 | 61906;61907;61908 | chr2:178554471;178554470;178554469 | chr2:179419198;179419197;179419196 |
| Novex-1 | 20686 | 62281;62282;62283 | chr2:178554471;178554470;178554469 | chr2:179419198;179419197;179419196 |
| Novex-2 | 20753 | 62482;62483;62484 | chr2:178554471;178554470;178554469 | chr2:179419198;179419197;179419196 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs766178585  |
-1.09 | 0.012 | N | 0.391 | 0.19 | 0.392547445146 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| V/A | rs766178585 |
-1.09 | 0.012 | N | 0.391 | 0.19 | 0.392547445146 | gnomAD-4.0.0 | 2.73772E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.50836E-05 | 0 | 1.65722E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1867 | likely_benign | 0.1878 | benign | -0.898 | Destabilizing | 0.012 | N | 0.391 | neutral | N | 0.483580328 | None | None | N |
| V/C | 0.6781 | likely_pathogenic | 0.6904 | pathogenic | -0.854 | Destabilizing | 0.869 | D | 0.481 | neutral | None | None | None | None | N |
| V/D | 0.5329 | ambiguous | 0.532 | ambiguous | -0.327 | Destabilizing | 0.221 | N | 0.649 | prob.neutral | None | None | None | None | N |
| V/E | 0.3304 | likely_benign | 0.3284 | benign | -0.375 | Destabilizing | 0.177 | N | 0.576 | neutral | N | 0.471970534 | None | None | N |
| V/F | 0.1662 | likely_benign | 0.1726 | benign | -0.733 | Destabilizing | 0.221 | N | 0.543 | neutral | None | None | None | None | N |
| V/G | 0.3926 | ambiguous | 0.3805 | ambiguous | -1.14 | Destabilizing | 0.177 | N | 0.631 | neutral | N | 0.485101266 | None | None | N |
| V/H | 0.5499 | ambiguous | 0.5541 | ambiguous | -0.575 | Destabilizing | 0.869 | D | 0.635 | neutral | None | None | None | None | N |
| V/I | 0.0586 | likely_benign | 0.0602 | benign | -0.374 | Destabilizing | None | N | 0.088 | neutral | N | 0.418255879 | None | None | N |
| V/K | 0.3556 | ambiguous | 0.3423 | ambiguous | -0.752 | Destabilizing | 0.221 | N | 0.585 | neutral | None | None | None | None | N |
| V/L | 0.1151 | likely_benign | 0.1136 | benign | -0.374 | Destabilizing | None | N | 0.173 | neutral | N | 0.456427478 | None | None | N |
| V/M | 0.1045 | likely_benign | 0.1104 | benign | -0.417 | Destabilizing | 0.221 | N | 0.502 | neutral | None | None | None | None | N |
| V/N | 0.3265 | likely_benign | 0.3227 | benign | -0.556 | Destabilizing | 0.221 | N | 0.673 | prob.neutral | None | None | None | None | N |
| V/P | 0.4945 | ambiguous | 0.5046 | ambiguous | -0.512 | Destabilizing | 0.366 | N | 0.627 | neutral | None | None | None | None | N |
| V/Q | 0.3206 | likely_benign | 0.3208 | benign | -0.727 | Destabilizing | 0.366 | N | 0.57 | neutral | None | None | None | None | N |
| V/R | 0.3358 | likely_benign | 0.3236 | benign | -0.255 | Destabilizing | 0.221 | N | 0.647 | neutral | None | None | None | None | N |
| V/S | 0.2667 | likely_benign | 0.2571 | benign | -1.079 | Destabilizing | 0.039 | N | 0.571 | neutral | None | None | None | None | N |
| V/T | 0.1241 | likely_benign | 0.127 | benign | -1.01 | Destabilizing | None | N | 0.279 | neutral | None | None | None | None | N |
| V/W | 0.7393 | likely_pathogenic | 0.7802 | pathogenic | -0.838 | Destabilizing | 0.869 | D | 0.691 | prob.delet. | None | None | None | None | N |
| V/Y | 0.4943 | ambiguous | 0.5147 | ambiguous | -0.546 | Destabilizing | 0.366 | N | 0.532 | 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.