Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31659 | 95200;95201;95202 | chr2:178546356;178546355;178546354 | chr2:179411083;179411082;179411081 |
| N2AB | 30018 | 90277;90278;90279 | chr2:178546356;178546355;178546354 | chr2:179411083;179411082;179411081 |
| N2A | 29091 | 87496;87497;87498 | chr2:178546356;178546355;178546354 | chr2:179411083;179411082;179411081 |
| N2B | 22594 | 68005;68006;68007 | chr2:178546356;178546355;178546354 | chr2:179411083;179411082;179411081 |
| Novex-1 | 22719 | 68380;68381;68382 | chr2:178546356;178546355;178546354 | chr2:179411083;179411082;179411081 |
| Novex-2 | 22786 | 68581;68582;68583 | chr2:178546356;178546355;178546354 | chr2:179411083;179411082;179411081 |
| 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 | rs747276133  |
-0.818 | 0.975 | N | 0.427 | 0.382 | 0.532263770911 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| C/Y | rs747276133 |
-0.818 | 0.975 | N | 0.427 | 0.382 | 0.532263770911 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| C/Y | rs747276133 |
-0.818 | 0.975 | N | 0.427 | 0.382 | 0.532263770911 | gnomAD-4.0.0 | 6.57367E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47011E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/A | 0.2148 | likely_benign | 0.2371 | benign | -0.576 | Destabilizing | 0.176 | N | 0.223 | neutral | None | None | None | None | N |
| C/D | 0.3653 | ambiguous | 0.3641 | ambiguous | 0.528 | Stabilizing | 0.704 | D | 0.451 | neutral | None | None | None | None | N |
| C/E | 0.5654 | likely_pathogenic | 0.5821 | pathogenic | 0.497 | Stabilizing | 0.704 | D | 0.485 | neutral | None | None | None | None | N |
| C/F | 0.1735 | likely_benign | 0.1911 | benign | -0.544 | Destabilizing | 0.975 | D | 0.433 | neutral | N | 0.445644764 | None | None | N |
| C/G | 0.0708 | likely_benign | 0.0676 | benign | -0.711 | Destabilizing | 0.001 | N | 0.235 | neutral | N | 0.353211818 | None | None | N |
| C/H | 0.3008 | likely_benign | 0.3113 | benign | -0.632 | Destabilizing | 0.981 | D | 0.434 | neutral | None | None | None | None | N |
| C/I | 0.4857 | ambiguous | 0.5429 | ambiguous | -0.308 | Destabilizing | 0.828 | D | 0.421 | neutral | None | None | None | None | N |
| C/K | 0.5291 | ambiguous | 0.5327 | ambiguous | 0.073 | Stabilizing | 0.704 | D | 0.445 | neutral | None | None | None | None | N |
| C/L | 0.2966 | likely_benign | 0.3198 | benign | -0.308 | Destabilizing | 0.704 | D | 0.355 | neutral | None | None | None | None | N |
| C/M | 0.4484 | ambiguous | 0.4826 | ambiguous | 0.047 | Stabilizing | 0.981 | D | 0.323 | neutral | None | None | None | None | N |
| C/N | 0.206 | likely_benign | 0.2061 | benign | 0.363 | Stabilizing | 0.704 | D | 0.446 | neutral | None | None | None | None | N |
| C/P | 0.775 | likely_pathogenic | 0.7845 | pathogenic | -0.373 | Destabilizing | 0.944 | D | 0.501 | neutral | None | None | None | None | N |
| C/Q | 0.3783 | ambiguous | 0.3979 | ambiguous | 0.237 | Stabilizing | 0.944 | D | 0.492 | neutral | None | None | None | None | N |
| C/R | 0.2542 | likely_benign | 0.262 | benign | 0.379 | Stabilizing | 0.863 | D | 0.495 | neutral | N | 0.404720861 | None | None | N |
| C/S | 0.0982 | likely_benign | 0.1039 | benign | -0.1 | Destabilizing | 0.01 | N | 0.18 | neutral | N | 0.328294731 | None | None | N |
| C/T | 0.1989 | likely_benign | 0.2094 | benign | -0.005 | Destabilizing | 0.329 | N | 0.353 | neutral | None | None | None | None | N |
| C/V | 0.3599 | ambiguous | 0.3972 | ambiguous | -0.373 | Destabilizing | 0.704 | D | 0.372 | neutral | None | None | None | None | N |
| C/W | 0.4031 | ambiguous | 0.4232 | ambiguous | -0.523 | Destabilizing | 0.993 | D | 0.392 | neutral | N | 0.464673242 | None | None | N |
| C/Y | 0.2343 | likely_benign | 0.2558 | benign | -0.383 | Destabilizing | 0.975 | D | 0.427 | neutral | N | 0.445644764 | 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.