Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15078 | 45457;45458;45459 | chr2:178621592;178621591;178621590 | chr2:179486319;179486318;179486317 |
| N2AB | 13437 | 40534;40535;40536 | chr2:178621592;178621591;178621590 | chr2:179486319;179486318;179486317 |
| N2A | 12510 | 37753;37754;37755 | chr2:178621592;178621591;178621590 | chr2:179486319;179486318;179486317 |
| N2B | 6013 | 18262;18263;18264 | chr2:178621592;178621591;178621590 | chr2:179486319;179486318;179486317 |
| Novex-1 | 6138 | 18637;18638;18639 | chr2:178621592;178621591;178621590 | chr2:179486319;179486318;179486317 |
| Novex-2 | 6205 | 18838;18839;18840 | chr2:178621592;178621591;178621590 | chr2:179486319;179486318;179486317 |
| 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/L | rs756536427  |
-0.645 | 0.004 | N | 0.276 | 0.159 | 0.492404595834 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 2.91E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/L | rs756536427 |
-0.645 | 0.004 | N | 0.276 | 0.159 | 0.492404595834 | gnomAD-4.0.0 | 6.8465E-07 | None | None | None | None | N | None | 0 | 2.24095E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | None | None | 0.028 | N | 0.293 | 0.107 | 0.433936292671 | gnomAD-4.0.0 | 6.8465E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99915E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.5042 | ambiguous | 0.4493 | ambiguous | -2.196 | Highly Destabilizing | 0.036 | N | 0.289 | neutral | None | None | None | None | N |
| I/C | 0.6861 | likely_pathogenic | 0.6474 | pathogenic | -1.317 | Destabilizing | 0.901 | D | 0.513 | neutral | None | None | None | None | N |
| I/D | 0.7578 | likely_pathogenic | 0.6852 | pathogenic | -2.275 | Highly Destabilizing | 0.148 | N | 0.435 | neutral | None | None | None | None | N |
| I/E | 0.6589 | likely_pathogenic | 0.5932 | pathogenic | -2.126 | Highly Destabilizing | 0.08 | N | 0.353 | neutral | None | None | None | None | N |
| I/F | 0.1316 | likely_benign | 0.123 | benign | -1.35 | Destabilizing | 0.174 | N | 0.426 | neutral | None | None | None | None | N |
| I/G | 0.7421 | likely_pathogenic | 0.6936 | pathogenic | -2.665 | Highly Destabilizing | 0.148 | N | 0.388 | neutral | None | None | None | None | N |
| I/H | 0.4407 | ambiguous | 0.3821 | ambiguous | -1.983 | Destabilizing | None | N | 0.304 | neutral | None | None | None | None | N |
| I/K | 0.4169 | ambiguous | 0.3631 | ambiguous | -1.725 | Destabilizing | 0.061 | N | 0.377 | neutral | N | 0.521248991 | None | None | N |
| I/L | 0.1337 | likely_benign | 0.1345 | benign | -0.889 | Destabilizing | 0.004 | N | 0.276 | neutral | N | 0.387873407 | None | None | N |
| I/M | 0.104 | likely_benign | 0.0943 | benign | -0.664 | Destabilizing | 0.004 | N | 0.224 | neutral | N | 0.473445403 | None | None | N |
| I/N | 0.2641 | likely_benign | 0.213 | benign | -1.854 | Destabilizing | 0.148 | N | 0.434 | neutral | None | None | None | None | N |
| I/P | 0.8329 | likely_pathogenic | 0.8561 | pathogenic | -1.301 | Destabilizing | 0.46 | N | 0.585 | neutral | None | None | None | None | N |
| I/Q | 0.4624 | ambiguous | 0.4139 | ambiguous | -1.848 | Destabilizing | 0.002 | N | 0.319 | neutral | None | None | None | None | N |
| I/R | 0.3396 | likely_benign | 0.293 | benign | -1.265 | Destabilizing | 0.061 | N | 0.486 | neutral | N | 0.517134822 | None | None | N |
| I/S | 0.3866 | ambiguous | 0.3205 | benign | -2.495 | Highly Destabilizing | 0.08 | N | 0.342 | neutral | None | None | None | None | N |
| I/T | 0.3441 | ambiguous | 0.2909 | benign | -2.215 | Highly Destabilizing | None | N | 0.146 | neutral | N | 0.514127773 | None | None | N |
| I/V | 0.1209 | likely_benign | 0.1124 | benign | -1.301 | Destabilizing | 0.028 | N | 0.293 | neutral | N | 0.4676362 | None | None | N |
| I/W | 0.6985 | likely_pathogenic | 0.6609 | pathogenic | -1.67 | Destabilizing | 0.749 | D | 0.566 | neutral | None | None | None | None | N |
| I/Y | 0.368 | ambiguous | 0.3375 | benign | -1.37 | Destabilizing | 0.001 | N | 0.174 | 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.