Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17481 | 52666;52667;52668 | chr2:178608442;178608441;178608440 | chr2:179473169;179473168;179473167 |
| N2AB | 15840 | 47743;47744;47745 | chr2:178608442;178608441;178608440 | chr2:179473169;179473168;179473167 |
| N2A | 14913 | 44962;44963;44964 | chr2:178608442;178608441;178608440 | chr2:179473169;179473168;179473167 |
| N2B | 8416 | 25471;25472;25473 | chr2:178608442;178608441;178608440 | chr2:179473169;179473168;179473167 |
| Novex-1 | 8541 | 25846;25847;25848 | chr2:178608442;178608441;178608440 | chr2:179473169;179473168;179473167 |
| Novex-2 | 8608 | 26047;26048;26049 | chr2:178608442;178608441;178608440 | chr2:179473169;179473168;179473167 |
| 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 | None | None | 0.117 | N | 0.237 | 0.028 | 0.110078149338 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 6.07533E-05 | 0 |
| D/G | rs773362408  |
-0.214 | 0.977 | N | 0.632 | 0.492 | 0.257292322809 | gnomAD-2.1.1 | 1.26E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.02733E-04 | None | 0 | 0 | 0 |
| D/G | rs773362408 |
-0.214 | 0.977 | N | 0.632 | 0.492 | 0.257292322809 | gnomAD-4.0.0 | 3.43631E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 5.86497E-05 | 0 |
| D/H | rs975141016 |
None | 0.999 | N | 0.621 | 0.449 | 0.296329037015 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/H | rs975141016 |
None | 0.999 | N | 0.621 | 0.449 | 0.296329037015 | gnomAD-4.0.0 | 3.87762E-06 | None | None | None | None | N | None | 5.08889E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 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 | 0.1451 | likely_benign | 0.1345 | benign | -0.291 | Destabilizing | 0.993 | D | 0.594 | neutral | N | 0.49167899 | None | None | N |
| D/C | 0.5941 | likely_pathogenic | 0.5196 | ambiguous | 0.047 | Stabilizing | 1.0 | D | 0.65 | neutral | None | None | None | None | N |
| D/E | 0.1443 | likely_benign | 0.135 | benign | -0.355 | Destabilizing | 0.117 | N | 0.237 | neutral | N | 0.455891548 | None | None | N |
| D/F | 0.6008 | likely_pathogenic | 0.516 | ambiguous | -0.212 | Destabilizing | 1.0 | D | 0.642 | neutral | None | None | None | None | N |
| D/G | 0.1282 | likely_benign | 0.1208 | benign | -0.499 | Destabilizing | 0.977 | D | 0.632 | neutral | N | 0.470723675 | None | None | N |
| D/H | 0.2952 | likely_benign | 0.2616 | benign | -0.096 | Destabilizing | 0.999 | D | 0.621 | neutral | N | 0.476866194 | None | None | N |
| D/I | 0.4345 | ambiguous | 0.3681 | ambiguous | 0.211 | Stabilizing | 0.998 | D | 0.696 | prob.neutral | None | None | None | None | N |
| D/K | 0.3049 | likely_benign | 0.3004 | benign | 0.339 | Stabilizing | 0.99 | D | 0.625 | neutral | None | None | None | None | N |
| D/L | 0.4041 | ambiguous | 0.3591 | ambiguous | 0.211 | Stabilizing | 0.995 | D | 0.683 | prob.neutral | None | None | None | None | N |
| D/M | 0.5504 | ambiguous | 0.4794 | ambiguous | 0.354 | Stabilizing | 1.0 | D | 0.638 | neutral | None | None | None | None | N |
| D/N | 0.0941 | likely_benign | 0.0853 | benign | -0.006 | Destabilizing | 0.993 | D | 0.631 | neutral | N | 0.496450091 | None | None | N |
| D/P | 0.8868 | likely_pathogenic | 0.8672 | pathogenic | 0.066 | Stabilizing | 0.998 | D | 0.68 | prob.neutral | None | None | None | None | N |
| D/Q | 0.3029 | likely_benign | 0.2845 | benign | 0.026 | Stabilizing | 0.99 | D | 0.684 | prob.neutral | None | None | None | None | N |
| D/R | 0.37 | ambiguous | 0.3536 | ambiguous | 0.486 | Stabilizing | 0.995 | D | 0.667 | neutral | None | None | None | None | N |
| D/S | 0.1382 | likely_benign | 0.1265 | benign | -0.104 | Destabilizing | 0.983 | D | 0.589 | neutral | None | None | None | None | N |
| D/T | 0.256 | likely_benign | 0.2176 | benign | 0.058 | Stabilizing | 0.995 | D | 0.679 | prob.neutral | None | None | None | None | N |
| D/V | 0.2541 | likely_benign | 0.2143 | benign | 0.066 | Stabilizing | 0.997 | D | 0.692 | prob.neutral | N | 0.489588398 | None | None | N |
| D/W | 0.8491 | likely_pathogenic | 0.812 | pathogenic | -0.071 | Destabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | N |
| D/Y | 0.2195 | likely_benign | 0.1792 | benign | 0.032 | Stabilizing | 1.0 | D | 0.641 | neutral | N | 0.502212151 | 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.