Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 8413 | 25462;25463;25464 | chr2:178717637;178717636;178717635 | chr2:179582364;179582363;179582362 |
| N2AB | 8096 | 24511;24512;24513 | chr2:178717637;178717636;178717635 | chr2:179582364;179582363;179582362 |
| N2A | 7169 | 21730;21731;21732 | chr2:178717637;178717636;178717635 | chr2:179582364;179582363;179582362 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/K | rs772142595  |
0.066 | 0.006 | N | 0.197 | 0.131 | 0.158396225186 | gnomAD-2.1.1 | 8.08E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.56E-05 | None | 0 | 0 | 0 |
| N/K | rs772142595 |
0.066 | 0.006 | N | 0.197 | 0.131 | 0.158396225186 | gnomAD-4.0.0 | 3.1847E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.8687E-05 | 0 |
| N/Y | rs971543383 |
None | 0.762 | D | 0.722 | 0.411 | 0.70240400353 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| N/Y | rs971543383 |
None | 0.762 | D | 0.722 | 0.411 | 0.70240400353 | gnomAD-4.0.0 | 2.56372E-06 | None | None | None | None | N | None | 1.69216E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 2.84706E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.5062 | ambiguous | 0.5247 | ambiguous | -0.884 | Destabilizing | 0.031 | N | 0.609 | neutral | None | None | None | None | N |
| N/C | 0.6166 | likely_pathogenic | 0.6063 | pathogenic | -0.049 | Destabilizing | 0.982 | D | 0.744 | deleterious | None | None | None | None | N |
| N/D | 0.2045 | likely_benign | 0.2092 | benign | -0.433 | Destabilizing | 0.128 | N | 0.483 | neutral | N | 0.512201482 | None | None | N |
| N/E | 0.6211 | likely_pathogenic | 0.6229 | pathogenic | -0.283 | Destabilizing | 0.244 | N | 0.472 | neutral | None | None | None | None | N |
| N/F | 0.848 | likely_pathogenic | 0.8574 | pathogenic | -0.537 | Destabilizing | 0.894 | D | 0.735 | prob.delet. | None | None | None | None | N |
| N/G | 0.2928 | likely_benign | 0.307 | benign | -1.261 | Destabilizing | 0.619 | D | 0.433 | neutral | None | None | None | None | N |
| N/H | 0.1263 | likely_benign | 0.1272 | benign | -0.793 | Destabilizing | 0.005 | N | 0.206 | neutral | N | 0.513155562 | None | None | N |
| N/I | 0.7937 | likely_pathogenic | 0.8218 | pathogenic | 0.096 | Stabilizing | 0.829 | D | 0.733 | prob.delet. | D | 0.524765357 | None | None | N |
| N/K | 0.4901 | ambiguous | 0.4694 | ambiguous | -0.109 | Destabilizing | 0.006 | N | 0.197 | neutral | N | 0.518396736 | None | None | N |
| N/L | 0.6214 | likely_pathogenic | 0.6409 | pathogenic | 0.096 | Stabilizing | 0.76 | D | 0.685 | prob.neutral | None | None | None | None | N |
| N/M | 0.7226 | likely_pathogenic | 0.7284 | pathogenic | 0.349 | Stabilizing | 0.987 | D | 0.711 | prob.delet. | None | None | None | None | N |
| N/P | 0.8951 | likely_pathogenic | 0.8998 | pathogenic | -0.201 | Destabilizing | 0.58 | D | 0.723 | prob.delet. | None | None | None | None | N |
| N/Q | 0.4351 | ambiguous | 0.4396 | ambiguous | -0.662 | Destabilizing | 0.613 | D | 0.531 | neutral | None | None | None | None | N |
| N/R | 0.4659 | ambiguous | 0.4699 | ambiguous | -0.198 | Destabilizing | 0.547 | D | 0.503 | neutral | None | None | None | None | N |
| N/S | 0.1201 | likely_benign | 0.1238 | benign | -0.92 | Destabilizing | 0.006 | N | 0.219 | neutral | N | 0.482730269 | None | None | N |
| N/T | 0.3728 | ambiguous | 0.3774 | ambiguous | -0.558 | Destabilizing | 0.185 | N | 0.452 | neutral | N | 0.490669987 | None | None | N |
| N/V | 0.7765 | likely_pathogenic | 0.7948 | pathogenic | -0.201 | Destabilizing | 0.21 | N | 0.703 | prob.neutral | None | None | None | None | N |
| N/W | 0.9049 | likely_pathogenic | 0.9094 | pathogenic | -0.296 | Destabilizing | 0.995 | D | 0.743 | deleterious | None | None | None | None | N |
| N/Y | 0.3736 | ambiguous | 0.3937 | ambiguous | -0.052 | Destabilizing | 0.762 | D | 0.722 | prob.delet. | D | 0.524511867 | 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.