Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31354 | 94285;94286;94287 | chr2:178547566;178547565;178547564 | chr2:179412293;179412292;179412291 |
| N2AB | 29713 | 89362;89363;89364 | chr2:178547566;178547565;178547564 | chr2:179412293;179412292;179412291 |
| N2A | 28786 | 86581;86582;86583 | chr2:178547566;178547565;178547564 | chr2:179412293;179412292;179412291 |
| N2B | 22289 | 67090;67091;67092 | chr2:178547566;178547565;178547564 | chr2:179412293;179412292;179412291 |
| Novex-1 | 22414 | 67465;67466;67467 | chr2:178547566;178547565;178547564 | chr2:179412293;179412292;179412291 |
| Novex-2 | 22481 | 67666;67667;67668 | chr2:178547566;178547565;178547564 | chr2:179412293;179412292;179412291 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs930361700  |
None | 0.998 | N | 0.579 | 0.364 | 0.383921772103 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.78011E-04 |
| T/I | rs930361700 |
None | 0.998 | N | 0.579 | 0.364 | 0.383921772103 | gnomAD-4.0.0 | 3.7181E-06 | None | None | None | None | N | None | 5.33832E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.47593E-07 | 0 | 1.60113E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0857 | likely_benign | 0.0761 | benign | -0.175 | Destabilizing | 0.333 | N | 0.345 | neutral | N | 0.451179161 | None | None | N |
| T/C | 0.6473 | likely_pathogenic | 0.5685 | pathogenic | -0.363 | Destabilizing | 1.0 | D | 0.577 | neutral | None | None | None | None | N |
| T/D | 0.638 | likely_pathogenic | 0.5659 | pathogenic | 0.038 | Stabilizing | 0.999 | D | 0.576 | neutral | None | None | None | None | N |
| T/E | 0.5346 | ambiguous | 0.4801 | ambiguous | -0.049 | Destabilizing | 0.999 | D | 0.555 | neutral | None | None | None | None | N |
| T/F | 0.5118 | ambiguous | 0.4596 | ambiguous | -0.832 | Destabilizing | 1.0 | D | 0.593 | neutral | None | None | None | None | N |
| T/G | 0.2917 | likely_benign | 0.2451 | benign | -0.239 | Destabilizing | 0.992 | D | 0.519 | neutral | None | None | None | None | N |
| T/H | 0.4976 | ambiguous | 0.4236 | ambiguous | -0.346 | Destabilizing | 1.0 | D | 0.59 | neutral | None | None | None | None | N |
| T/I | 0.3222 | likely_benign | 0.2762 | benign | -0.129 | Destabilizing | 0.998 | D | 0.579 | neutral | N | 0.473690662 | None | None | N |
| T/K | 0.404 | ambiguous | 0.3658 | ambiguous | -0.268 | Destabilizing | 0.998 | D | 0.561 | neutral | N | 0.453256674 | None | None | N |
| T/L | 0.1402 | likely_benign | 0.1243 | benign | -0.129 | Destabilizing | 0.992 | D | 0.56 | neutral | None | None | None | None | N |
| T/M | 0.1061 | likely_benign | 0.0985 | benign | -0.219 | Destabilizing | 1.0 | D | 0.567 | neutral | None | None | None | None | N |
| T/N | 0.212 | likely_benign | 0.1845 | benign | -0.053 | Destabilizing | 1.0 | D | 0.582 | neutral | None | None | None | None | N |
| T/P | 0.1556 | likely_benign | 0.1299 | benign | -0.12 | Destabilizing | 0.998 | D | 0.573 | neutral | N | 0.485310378 | None | None | N |
| T/Q | 0.382 | ambiguous | 0.3305 | benign | -0.252 | Destabilizing | 1.0 | D | 0.563 | neutral | None | None | None | None | N |
| T/R | 0.3652 | ambiguous | 0.3368 | benign | 0.042 | Stabilizing | 0.998 | D | 0.566 | neutral | N | 0.456817054 | None | None | N |
| T/S | 0.1459 | likely_benign | 0.1264 | benign | -0.223 | Destabilizing | 0.978 | D | 0.55 | neutral | N | 0.447157421 | None | None | N |
| T/V | 0.1887 | likely_benign | 0.16 | benign | -0.12 | Destabilizing | 0.992 | D | 0.528 | neutral | None | None | None | None | N |
| T/W | 0.8403 | likely_pathogenic | 0.7936 | pathogenic | -0.925 | Destabilizing | 1.0 | D | 0.643 | neutral | None | None | None | None | N |
| T/Y | 0.6033 | likely_pathogenic | 0.5236 | ambiguous | -0.598 | Destabilizing | 1.0 | D | 0.588 | 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.