Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 34274 | 103045;103046;103047 | chr2:178533795;178533794;178533793 | chr2:179398522;179398521;179398520 |
| N2AB | 32633 | 98122;98123;98124 | chr2:178533795;178533794;178533793 | chr2:179398522;179398521;179398520 |
| N2A | 31706 | 95341;95342;95343 | chr2:178533795;178533794;178533793 | chr2:179398522;179398521;179398520 |
| N2B | 25209 | 75850;75851;75852 | chr2:178533795;178533794;178533793 | chr2:179398522;179398521;179398520 |
| Novex-1 | 25334 | 76225;76226;76227 | chr2:178533795;178533794;178533793 | chr2:179398522;179398521;179398520 |
| Novex-2 | 25401 | 76426;76427;76428 | chr2:178533795;178533794;178533793 | chr2:179398522;179398521;179398520 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/H | rs748399505  |
-0.85 | 0.004 | N | 0.203 | 0.097 | 0.0954503805726 | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.63388E-04 | None | 0 | 0 | 0 |
| N/H | rs748399505 |
-0.85 | 0.004 | N | 0.203 | 0.097 | 0.0954503805726 | gnomAD-4.0.0 | 1.11369E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.00289E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.2773 | likely_benign | 0.3068 | benign | -0.561 | Destabilizing | 0.129 | N | 0.387 | neutral | None | None | None | None | N |
| N/C | 0.417 | ambiguous | 0.5013 | ambiguous | 0.277 | Stabilizing | 0.983 | D | 0.461 | neutral | None | None | None | None | N |
| N/D | 0.1069 | likely_benign | 0.1154 | benign | -0.28 | Destabilizing | 0.001 | N | 0.15 | neutral | N | 0.383120933 | None | None | N |
| N/E | 0.4008 | ambiguous | 0.4199 | ambiguous | -0.281 | Destabilizing | 0.129 | N | 0.255 | neutral | None | None | None | None | N |
| N/F | 0.7008 | likely_pathogenic | 0.7478 | pathogenic | -0.767 | Destabilizing | 0.836 | D | 0.46 | neutral | None | None | None | None | N |
| N/G | 0.3896 | ambiguous | 0.437 | ambiguous | -0.791 | Destabilizing | 0.001 | N | 0.137 | neutral | None | None | None | None | N |
| N/H | 0.1489 | likely_benign | 0.1715 | benign | -0.792 | Destabilizing | 0.004 | N | 0.203 | neutral | N | 0.465912888 | None | None | N |
| N/I | 0.3228 | likely_benign | 0.3698 | ambiguous | -0.025 | Destabilizing | 0.487 | N | 0.486 | neutral | N | 0.484498648 | None | None | N |
| N/K | 0.3153 | likely_benign | 0.3534 | ambiguous | -0.017 | Destabilizing | 0.351 | N | 0.223 | neutral | N | 0.438110211 | None | None | N |
| N/L | 0.3995 | ambiguous | 0.4348 | ambiguous | -0.025 | Destabilizing | 0.264 | N | 0.437 | neutral | None | None | None | None | N |
| N/M | 0.4193 | ambiguous | 0.461 | ambiguous | 0.532 | Stabilizing | 0.951 | D | 0.421 | neutral | None | None | None | None | N |
| N/P | 0.5373 | ambiguous | 0.5407 | ambiguous | -0.175 | Destabilizing | 0.836 | D | 0.457 | neutral | None | None | None | None | N |
| N/Q | 0.403 | ambiguous | 0.4314 | ambiguous | -0.632 | Destabilizing | 0.836 | D | 0.366 | neutral | None | None | None | None | N |
| N/R | 0.3906 | ambiguous | 0.4431 | ambiguous | 0.068 | Stabilizing | 0.418 | N | 0.321 | neutral | None | None | None | None | N |
| N/S | 0.1064 | likely_benign | 0.1145 | benign | -0.389 | Destabilizing | 0.101 | N | 0.313 | neutral | N | 0.411190181 | None | None | N |
| N/T | 0.1344 | likely_benign | 0.1468 | benign | -0.229 | Destabilizing | 0.001 | N | 0.133 | neutral | N | 0.367554047 | None | None | N |
| N/V | 0.33 | likely_benign | 0.367 | ambiguous | -0.175 | Destabilizing | 0.264 | N | 0.472 | neutral | None | None | None | None | N |
| N/W | 0.8489 | likely_pathogenic | 0.8779 | pathogenic | -0.638 | Destabilizing | 0.983 | D | 0.511 | neutral | None | None | None | None | N |
| N/Y | 0.2434 | likely_benign | 0.2907 | benign | -0.401 | Destabilizing | 0.655 | D | 0.436 | neutral | N | 0.493830208 | 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.