Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16472 | 49639;49640;49641 | chr2:178613869;178613868;178613867 | chr2:179478596;179478595;179478594 |
| N2AB | 14831 | 44716;44717;44718 | chr2:178613869;178613868;178613867 | chr2:179478596;179478595;179478594 |
| N2A | 13904 | 41935;41936;41937 | chr2:178613869;178613868;178613867 | chr2:179478596;179478595;179478594 |
| N2B | 7407 | 22444;22445;22446 | chr2:178613869;178613868;178613867 | chr2:179478596;179478595;179478594 |
| Novex-1 | 7532 | 22819;22820;22821 | chr2:178613869;178613868;178613867 | chr2:179478596;179478595;179478594 |
| Novex-2 | 7599 | 23020;23021;23022 | chr2:178613869;178613868;178613867 | chr2:179478596;179478595;179478594 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/Y | rs766554662  |
-1.053 | 0.002 | N | 0.211 | 0.262 | 0.429435026966 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| C/Y | rs766554662 |
-1.053 | 0.002 | N | 0.211 | 0.262 | 0.429435026966 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| C/Y | rs766554662 |
-1.053 | 0.002 | N | 0.211 | 0.262 | 0.429435026966 | gnomAD-4.0.0 | 3.72256E-06 | None | None | None | None | N | None | 1.33701E-05 | 0 | None | 1.01695E-04 | 0 | None | 0 | 0 | 1.69653E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/A | 0.3447 | ambiguous | 0.3064 | benign | -1.926 | Destabilizing | 0.111 | N | 0.251 | neutral | None | None | None | None | N |
| C/D | 0.5635 | ambiguous | 0.5152 | ambiguous | -0.993 | Destabilizing | 0.223 | N | 0.357 | neutral | None | None | None | None | N |
| C/E | 0.6172 | likely_pathogenic | 0.5761 | pathogenic | -0.879 | Destabilizing | 0.365 | N | 0.355 | neutral | None | None | None | None | N |
| C/F | 0.1816 | likely_benign | 0.1601 | benign | -1.201 | Destabilizing | 0.178 | N | 0.349 | neutral | N | 0.433426314 | None | None | N |
| C/G | 0.2124 | likely_benign | 0.1805 | benign | -2.246 | Highly Destabilizing | 0.178 | N | 0.256 | neutral | N | 0.403048499 | None | None | N |
| C/H | 0.3835 | ambiguous | 0.324 | benign | -2.258 | Highly Destabilizing | 0.83 | D | 0.584 | neutral | None | None | None | None | N |
| C/I | 0.4445 | ambiguous | 0.4266 | ambiguous | -1.089 | Destabilizing | 0.223 | N | 0.305 | neutral | None | None | None | None | N |
| C/K | 0.6867 | likely_pathogenic | 0.6472 | pathogenic | -1.491 | Destabilizing | 0.365 | N | 0.357 | neutral | None | None | None | None | N |
| C/L | 0.3514 | ambiguous | 0.3225 | benign | -1.089 | Destabilizing | 0.111 | N | 0.237 | neutral | None | None | None | None | N |
| C/M | 0.4081 | ambiguous | 0.3817 | ambiguous | 0.065 | Stabilizing | 0.908 | D | 0.461 | neutral | None | None | None | None | N |
| C/N | 0.2734 | likely_benign | 0.2425 | benign | -1.484 | Destabilizing | 0.001 | N | 0.381 | neutral | None | None | None | None | N |
| C/P | 0.97 | likely_pathogenic | 0.9599 | pathogenic | -1.343 | Destabilizing | 0.896 | D | 0.555 | neutral | None | None | None | None | N |
| C/Q | 0.4524 | ambiguous | 0.3937 | ambiguous | -1.383 | Destabilizing | 0.738 | D | 0.515 | neutral | None | None | None | None | N |
| C/R | 0.4387 | ambiguous | 0.385 | ambiguous | -1.294 | Destabilizing | 0.512 | D | 0.496 | neutral | N | 0.358464525 | None | None | N |
| C/S | 0.2144 | likely_benign | 0.189 | benign | -1.993 | Destabilizing | 0.178 | N | 0.279 | neutral | N | 0.334827674 | None | None | N |
| C/T | 0.3378 | likely_benign | 0.2954 | benign | -1.707 | Destabilizing | 0.365 | N | 0.277 | neutral | None | None | None | None | N |
| C/V | 0.3626 | ambiguous | 0.3343 | benign | -1.343 | Destabilizing | 0.002 | N | 0.141 | neutral | None | None | None | None | N |
| C/W | 0.4367 | ambiguous | 0.3812 | ambiguous | -1.241 | Destabilizing | 0.882 | D | 0.486 | neutral | N | 0.479234529 | None | None | N |
| C/Y | 0.2176 | likely_benign | 0.1907 | benign | -1.253 | Destabilizing | 0.002 | N | 0.211 | neutral | N | 0.368846251 | 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.