Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2495 | 7708;7709;7710 | chr2:178773573;178773572;178773571 | chr2:179638300;179638299;179638298 |
| N2AB | 2495 | 7708;7709;7710 | chr2:178773573;178773572;178773571 | chr2:179638300;179638299;179638298 |
| N2A | 2495 | 7708;7709;7710 | chr2:178773573;178773572;178773571 | chr2:179638300;179638299;179638298 |
| N2B | 2449 | 7570;7571;7572 | chr2:178773573;178773572;178773571 | chr2:179638300;179638299;179638298 |
| Novex-1 | 2449 | 7570;7571;7572 | chr2:178773573;178773572;178773571 | chr2:179638300;179638299;179638298 |
| Novex-2 | 2449 | 7570;7571;7572 | chr2:178773573;178773572;178773571 | chr2:179638300;179638299;179638298 |
| Novex-3 | 2495 | 7708;7709;7710 | chr2:178773573;178773572;178773571 | chr2:179638300;179638299;179638298 |
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 | None | None | None | N | 0.235 | 0.207 | 0.485562757867 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| V/M | rs777701974  |
-0.289 | 0.427 | D | 0.497 | 0.103 | 0.416833835346 | gnomAD-2.1.1 | 4.38E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 2.94022E-04 | None | 0 | 1.76E-05 | 0 |
| V/M | rs777701974 |
-0.289 | 0.427 | D | 0.497 | 0.103 | 0.416833835346 | gnomAD-4.0.0 | 1.43662E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69794E-06 | 1.85499E-04 | 3.3117E-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 | 0.1447 | likely_benign | 0.1327 | benign | -0.844 | Destabilizing | None | N | 0.235 | neutral | N | 0.41623905 | None | None | N |
| V/C | 0.6095 | likely_pathogenic | 0.5552 | ambiguous | -0.791 | Destabilizing | 0.001 | N | 0.39 | neutral | None | None | None | None | N |
| V/D | 0.4961 | ambiguous | 0.4809 | ambiguous | -0.361 | Destabilizing | 0.22 | N | 0.587 | neutral | None | None | None | None | N |
| V/E | 0.4003 | ambiguous | 0.3925 | ambiguous | -0.436 | Destabilizing | 0.175 | N | 0.558 | neutral | N | 0.472921668 | None | None | N |
| V/F | 0.2013 | likely_benign | 0.1902 | benign | -0.823 | Destabilizing | 0.497 | N | 0.521 | neutral | None | None | None | None | N |
| V/G | 0.2092 | likely_benign | 0.1868 | benign | -1.055 | Destabilizing | 0.042 | N | 0.582 | neutral | N | 0.50782452 | None | None | N |
| V/H | 0.5825 | likely_pathogenic | 0.5519 | ambiguous | -0.604 | Destabilizing | 0.859 | D | 0.545 | neutral | None | None | None | None | N |
| V/I | 0.082 | likely_benign | 0.0808 | benign | -0.416 | Destabilizing | 0.001 | N | 0.233 | neutral | None | None | None | None | N |
| V/K | 0.4402 | ambiguous | 0.4256 | ambiguous | -0.691 | Destabilizing | 0.22 | N | 0.561 | neutral | None | None | None | None | N |
| V/L | 0.2233 | likely_benign | 0.2055 | benign | -0.416 | Destabilizing | 0.007 | N | 0.291 | neutral | N | 0.504247331 | None | None | N |
| V/M | 0.1609 | likely_benign | 0.153 | benign | -0.396 | Destabilizing | 0.427 | N | 0.497 | neutral | D | 0.533397478 | None | None | N |
| V/N | 0.2654 | likely_benign | 0.2473 | benign | -0.416 | Destabilizing | 0.22 | N | 0.574 | neutral | None | None | None | None | N |
| V/P | 0.6883 | likely_pathogenic | 0.6504 | pathogenic | -0.522 | Destabilizing | 0.364 | N | 0.571 | neutral | None | None | None | None | N |
| V/Q | 0.3317 | likely_benign | 0.3109 | benign | -0.633 | Destabilizing | 0.667 | D | 0.571 | neutral | None | None | None | None | N |
| V/R | 0.3836 | ambiguous | 0.3683 | ambiguous | -0.194 | Destabilizing | 0.497 | N | 0.581 | neutral | None | None | None | None | N |
| V/S | 0.1616 | likely_benign | 0.1464 | benign | -0.894 | Destabilizing | 0.002 | N | 0.416 | neutral | None | None | None | None | N |
| V/T | 0.1542 | likely_benign | 0.1439 | benign | -0.859 | Destabilizing | 0.055 | N | 0.386 | neutral | None | None | None | None | N |
| V/W | 0.8556 | likely_pathogenic | 0.8382 | pathogenic | -0.905 | Destabilizing | 0.958 | D | 0.551 | neutral | None | None | None | None | N |
| V/Y | 0.5795 | likely_pathogenic | 0.5472 | ambiguous | -0.616 | Destabilizing | 0.667 | D | 0.523 | 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.