Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33376 | 100351;100352;100353 | chr2:178536983;178536982;178536981 | chr2:179401710;179401709;179401708 |
| N2AB | 31735 | 95428;95429;95430 | chr2:178536983;178536982;178536981 | chr2:179401710;179401709;179401708 |
| N2A | 30808 | 92647;92648;92649 | chr2:178536983;178536982;178536981 | chr2:179401710;179401709;179401708 |
| N2B | 24311 | 73156;73157;73158 | chr2:178536983;178536982;178536981 | chr2:179401710;179401709;179401708 |
| Novex-1 | 24436 | 73531;73532;73533 | chr2:178536983;178536982;178536981 | chr2:179401710;179401709;179401708 |
| Novex-2 | 24503 | 73732;73733;73734 | chr2:178536983;178536982;178536981 | chr2:179401710;179401709;179401708 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs1691887188  |
None | None | N | 0.161 | 0.04 | 0.0297737177859 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.78927E-04 |
| D/E | rs1691887188 |
None | None | N | 0.161 | 0.04 | 0.0297737177859 | gnomAD-4.0.0 | 6.84438E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.16074E-05 | 0 |
| D/H | None | None | 0.295 | N | 0.494 | 0.137 | 0.177238962908 | gnomAD-4.0.0 | 6.84445E-07 | None | None | None | None | I | None | 2.98954E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | None | None | None | N | 0.185 | 0.103 | 0.158396225186 | gnomAD-4.0.0 | 6.84445E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65722E-05 |
| D/Y | None | None | 0.56 | N | 0.455 | 0.22 | 0.495038369364 | gnomAD-4.0.0 | 6.84445E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.16082E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1866 | likely_benign | 0.1482 | benign | -0.383 | Destabilizing | 0.012 | N | 0.429 | neutral | N | 0.516705146 | None | None | I |
| D/C | 0.6891 | likely_pathogenic | 0.5203 | ambiguous | 0.096 | Stabilizing | 0.864 | D | 0.473 | neutral | None | None | None | None | I |
| D/E | 0.1212 | likely_benign | 0.1147 | benign | -0.387 | Destabilizing | None | N | 0.161 | neutral | N | 0.422890908 | None | None | I |
| D/F | 0.7275 | likely_pathogenic | 0.6111 | pathogenic | -0.431 | Destabilizing | 0.628 | D | 0.459 | neutral | None | None | None | None | I |
| D/G | 0.2864 | likely_benign | 0.2099 | benign | -0.578 | Destabilizing | 0.012 | N | 0.469 | neutral | N | 0.469261509 | None | None | I |
| D/H | 0.3576 | ambiguous | 0.2457 | benign | -0.435 | Destabilizing | 0.295 | N | 0.494 | neutral | N | 0.483024124 | None | None | I |
| D/I | 0.3781 | ambiguous | 0.2752 | benign | 0.081 | Stabilizing | 0.356 | N | 0.468 | neutral | None | None | None | None | I |
| D/K | 0.2764 | likely_benign | 0.2073 | benign | 0.221 | Stabilizing | 0.016 | N | 0.451 | neutral | None | None | None | None | I |
| D/L | 0.3858 | ambiguous | 0.2927 | benign | 0.081 | Stabilizing | 0.072 | N | 0.472 | neutral | None | None | None | None | I |
| D/M | 0.6106 | likely_pathogenic | 0.5111 | ambiguous | 0.37 | Stabilizing | 0.628 | D | 0.448 | neutral | None | None | None | None | I |
| D/N | 0.1304 | likely_benign | 0.1006 | benign | -0.009 | Destabilizing | None | N | 0.185 | neutral | N | 0.514243631 | None | None | I |
| D/P | 0.5223 | ambiguous | 0.427 | ambiguous | -0.052 | Destabilizing | 0.136 | N | 0.496 | neutral | None | None | None | None | I |
| D/Q | 0.2922 | likely_benign | 0.2263 | benign | 0.005 | Stabilizing | 0.003 | N | 0.217 | neutral | None | None | None | None | I |
| D/R | 0.4266 | ambiguous | 0.3068 | benign | 0.296 | Stabilizing | 0.038 | N | 0.43 | neutral | None | None | None | None | I |
| D/S | 0.1472 | likely_benign | 0.1156 | benign | -0.125 | Destabilizing | 0.016 | N | 0.459 | neutral | None | None | None | None | I |
| D/T | 0.2626 | likely_benign | 0.2002 | benign | 0.023 | Stabilizing | 0.072 | N | 0.449 | neutral | None | None | None | None | I |
| D/V | 0.2477 | likely_benign | 0.1804 | benign | -0.052 | Destabilizing | 0.055 | N | 0.467 | neutral | N | 0.469728808 | None | None | I |
| D/W | 0.9148 | likely_pathogenic | 0.8635 | pathogenic | -0.32 | Destabilizing | 0.864 | D | 0.502 | neutral | None | None | None | None | I |
| D/Y | 0.3339 | likely_benign | 0.2353 | benign | -0.205 | Destabilizing | 0.56 | D | 0.455 | neutral | N | 0.497747791 | 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.