Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21153 | 63682;63683;63684 | chr2:178587950;178587949;178587948 | chr2:179452677;179452676;179452675 |
| N2AB | 19512 | 58759;58760;58761 | chr2:178587950;178587949;178587948 | chr2:179452677;179452676;179452675 |
| N2A | 18585 | 55978;55979;55980 | chr2:178587950;178587949;178587948 | chr2:179452677;179452676;179452675 |
| N2B | 12088 | 36487;36488;36489 | chr2:178587950;178587949;178587948 | chr2:179452677;179452676;179452675 |
| Novex-1 | 12213 | 36862;36863;36864 | chr2:178587950;178587949;178587948 | chr2:179452677;179452676;179452675 |
| Novex-2 | 12280 | 37063;37064;37065 | chr2:178587950;178587949;178587948 | chr2:179452677;179452676;179452675 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs772411127  |
-0.712 | 0.784 | N | 0.499 | 0.163 | None | gnomAD-2.1.1 | 4.38E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 6.63E-05 | None | 0 | 8.01E-05 | 0 |
| I/T | rs772411127 |
-0.712 | 0.784 | N | 0.499 | 0.163 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 7.36E-05 | 0 | 0 |
| I/T | rs772411127 |
-0.712 | 0.784 | N | 0.499 | 0.163 | None | gnomAD-4.0.0 | 1.86321E-05 | None | None | None | None | I | None | 1.33633E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.12215E-05 | 4.41199E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.2621 | likely_benign | 0.252 | benign | -1.242 | Destabilizing | 0.495 | N | 0.479 | neutral | None | None | None | None | I |
| I/C | 0.6224 | likely_pathogenic | 0.6461 | pathogenic | -0.778 | Destabilizing | 0.995 | D | 0.591 | neutral | None | None | None | None | I |
| I/D | 0.7183 | likely_pathogenic | 0.7161 | pathogenic | -0.654 | Destabilizing | 0.981 | D | 0.628 | neutral | None | None | None | None | I |
| I/E | 0.5418 | ambiguous | 0.5277 | ambiguous | -0.723 | Destabilizing | 0.981 | D | 0.616 | neutral | None | None | None | None | I |
| I/F | 0.1246 | likely_benign | 0.1225 | benign | -1.087 | Destabilizing | 0.642 | D | 0.468 | neutral | N | 0.498412961 | None | None | I |
| I/G | 0.639 | likely_pathogenic | 0.6349 | pathogenic | -1.476 | Destabilizing | 0.828 | D | 0.605 | neutral | None | None | None | None | I |
| I/H | 0.5283 | ambiguous | 0.5229 | ambiguous | -0.636 | Destabilizing | 0.995 | D | 0.639 | neutral | None | None | None | None | I |
| I/K | 0.4171 | ambiguous | 0.4077 | ambiguous | -0.653 | Destabilizing | 0.944 | D | 0.607 | neutral | None | None | None | None | I |
| I/L | 0.0833 | likely_benign | 0.0824 | benign | -0.718 | Destabilizing | 0.001 | N | 0.186 | neutral | N | 0.433169404 | None | None | I |
| I/M | 0.0817 | likely_benign | 0.0801 | benign | -0.502 | Destabilizing | 0.139 | N | 0.271 | neutral | N | 0.441732959 | None | None | I |
| I/N | 0.3463 | ambiguous | 0.3464 | ambiguous | -0.385 | Destabilizing | 0.975 | D | 0.631 | neutral | N | 0.492524352 | None | None | I |
| I/P | 0.5111 | ambiguous | 0.4994 | ambiguous | -0.86 | Destabilizing | 0.981 | D | 0.631 | neutral | None | None | None | None | I |
| I/Q | 0.4477 | ambiguous | 0.4309 | ambiguous | -0.674 | Destabilizing | 0.944 | D | 0.631 | neutral | None | None | None | None | I |
| I/R | 0.3297 | likely_benign | 0.3222 | benign | 0.007 | Stabilizing | 0.944 | D | 0.632 | neutral | None | None | None | None | I |
| I/S | 0.3002 | likely_benign | 0.297 | benign | -0.947 | Destabilizing | 0.784 | D | 0.605 | neutral | N | 0.483616867 | None | None | I |
| I/T | 0.1576 | likely_benign | 0.1522 | benign | -0.905 | Destabilizing | 0.784 | D | 0.499 | neutral | N | 0.45937457 | None | None | I |
| I/V | 0.084 | likely_benign | 0.0843 | benign | -0.86 | Destabilizing | 0.139 | N | 0.261 | neutral | N | 0.402809211 | None | None | I |
| I/W | 0.5482 | ambiguous | 0.5506 | ambiguous | -1.049 | Destabilizing | 0.007 | N | 0.451 | neutral | None | None | None | None | I |
| I/Y | 0.4077 | ambiguous | 0.4168 | ambiguous | -0.823 | Destabilizing | 0.704 | D | 0.577 | neutral | None | None | None | None | I |
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.