Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 4753 | 14482;14483;14484 | chr2:178738196;178738195;178738194 | chr2:179602923;179602922;179602921 |
| N2AB | 4436 | 13531;13532;13533 | chr2:178738196;178738195;178738194 | chr2:179602923;179602922;179602921 |
| N2A | 3509 | 10750;10751;10752 | chr2:178738196;178738195;178738194 | chr2:179602923;179602922;179602921 |
| N2B | 4390 | 13393;13394;13395 | chr2:178738196;178738195;178738194 | chr2:179602923;179602922;179602921 |
| Novex-1 | 4515 | 13768;13769;13770 | chr2:178738196;178738195;178738194 | chr2:179602923;179602922;179602921 |
| Novex-2 | 4582 | 13969;13970;13971 | chr2:178738196;178738195;178738194 | chr2:179602923;179602922;179602921 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs752678561  |
0.06 | 0.978 | N | 0.472 | 0.345 | 0.528461186488 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| Y/C | rs752678561 |
0.06 | 0.978 | N | 0.472 | 0.345 | 0.528461186488 | 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 |
| Y/C | rs752678561 |
0.06 | 0.978 | N | 0.472 | 0.345 | 0.528461186488 | gnomAD-4.0.0 | 2.47889E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.56226E-05 | 0 | 1.69522E-06 | 1.09789E-05 | 0 |
| Y/F | None | None | 0.001 | N | 0.2 | 0.267 | 0.27855597813 | gnomAD-4.0.0 | 1.36851E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52398E-05 | None | 0 | 0 | 0 | 0 | 1.65689E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.5956 | likely_pathogenic | 0.6768 | pathogenic | -1.844 | Destabilizing | 0.228 | N | 0.478 | neutral | None | None | None | None | N |
| Y/C | 0.2537 | likely_benign | 0.3487 | ambiguous | -0.7 | Destabilizing | 0.978 | D | 0.472 | neutral | N | 0.443044416 | None | None | N |
| Y/D | 0.2675 | likely_benign | 0.3263 | benign | -0.373 | Destabilizing | 0.351 | N | 0.519 | neutral | N | 0.440604188 | None | None | N |
| Y/E | 0.6929 | likely_pathogenic | 0.7644 | pathogenic | -0.284 | Destabilizing | 0.264 | N | 0.505 | neutral | None | None | None | None | N |
| Y/F | 0.134 | likely_benign | 0.1389 | benign | -0.599 | Destabilizing | 0.001 | N | 0.2 | neutral | N | 0.442889034 | None | None | N |
| Y/G | 0.3483 | ambiguous | 0.4108 | ambiguous | -2.156 | Highly Destabilizing | 0.418 | N | 0.513 | neutral | None | None | None | None | N |
| Y/H | 0.2493 | likely_benign | 0.2975 | benign | -0.618 | Destabilizing | 0.002 | N | 0.176 | neutral | N | 0.442620588 | None | None | N |
| Y/I | 0.6804 | likely_pathogenic | 0.7452 | pathogenic | -0.915 | Destabilizing | 0.264 | N | 0.495 | neutral | None | None | None | None | N |
| Y/K | 0.7361 | likely_pathogenic | 0.8047 | pathogenic | -0.934 | Destabilizing | 0.264 | N | 0.497 | neutral | None | None | None | None | N |
| Y/L | 0.555 | ambiguous | 0.6227 | pathogenic | -0.915 | Destabilizing | 0.129 | N | 0.449 | neutral | None | None | None | None | N |
| Y/M | 0.6926 | likely_pathogenic | 0.7438 | pathogenic | -0.693 | Destabilizing | 0.836 | D | 0.474 | neutral | None | None | None | None | N |
| Y/N | 0.1344 | likely_benign | 0.1611 | benign | -1.315 | Destabilizing | 0.213 | N | 0.513 | neutral | N | 0.440857277 | None | None | N |
| Y/P | 0.8883 | likely_pathogenic | 0.9231 | pathogenic | -1.218 | Destabilizing | 0.836 | D | 0.491 | neutral | None | None | None | None | N |
| Y/Q | 0.6134 | likely_pathogenic | 0.7101 | pathogenic | -1.174 | Destabilizing | 0.716 | D | 0.482 | neutral | None | None | None | None | N |
| Y/R | 0.6055 | likely_pathogenic | 0.7039 | pathogenic | -0.62 | Destabilizing | 0.002 | N | 0.383 | neutral | None | None | None | None | N |
| Y/S | 0.2812 | likely_benign | 0.3552 | ambiguous | -1.818 | Destabilizing | 0.213 | N | 0.473 | neutral | N | 0.441132102 | None | None | N |
| Y/T | 0.5282 | ambiguous | 0.6091 | pathogenic | -1.632 | Destabilizing | 0.004 | N | 0.261 | neutral | None | None | None | None | N |
| Y/V | 0.5754 | likely_pathogenic | 0.6412 | pathogenic | -1.218 | Destabilizing | 0.418 | N | 0.419 | neutral | None | None | None | None | N |
| Y/W | 0.5582 | ambiguous | 0.6163 | pathogenic | -0.268 | Destabilizing | 0.94 | D | 0.481 | 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.