Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31644 | 95155;95156;95157 | chr2:178546401;178546400;178546399 | chr2:179411128;179411127;179411126 |
| N2AB | 30003 | 90232;90233;90234 | chr2:178546401;178546400;178546399 | chr2:179411128;179411127;179411126 |
| N2A | 29076 | 87451;87452;87453 | chr2:178546401;178546400;178546399 | chr2:179411128;179411127;179411126 |
| N2B | 22579 | 67960;67961;67962 | chr2:178546401;178546400;178546399 | chr2:179411128;179411127;179411126 |
| Novex-1 | 22704 | 68335;68336;68337 | chr2:178546401;178546400;178546399 | chr2:179411128;179411127;179411126 |
| Novex-2 | 22771 | 68536;68537;68538 | chr2:178546401;178546400;178546399 | chr2:179411128;179411127;179411126 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/D | rs1281349835  |
-0.378 | 0.999 | N | 0.541 | 0.185 | 0.46017455471 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| E/D | rs1281349835 |
-0.378 | 0.999 | N | 0.541 | 0.185 | 0.46017455471 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| E/D | rs1281349835 |
-0.378 | 0.999 | N | 0.541 | 0.185 | 0.46017455471 | gnomAD-4.0.0 | 1.85912E-05 | None | None | None | None | I | None | 1.33483E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.45813E-05 | 0 | 0 |
| E/K | rs958594083 |
0.168 | 0.999 | N | 0.699 | 0.43 | 0.457286136841 | gnomAD-2.1.1 | 1.79E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.91E-05 | 0 |
| E/K | rs958594083 |
0.168 | 0.999 | N | 0.699 | 0.43 | 0.457286136841 | gnomAD-3.1.2 | 3.95E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 7.35E-05 | 0 | 0 |
| E/K | rs958594083 |
0.168 | 0.999 | N | 0.699 | 0.43 | 0.457286136841 | gnomAD-4.0.0 | 2.04513E-05 | None | None | None | None | I | None | 1.33518E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.71243E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.1537 | likely_benign | 0.1467 | benign | -0.235 | Destabilizing | 0.999 | D | 0.703 | prob.neutral | N | 0.457196349 | None | None | I |
| E/C | 0.8853 | likely_pathogenic | 0.8769 | pathogenic | -0.007 | Destabilizing | 1.0 | D | 0.673 | neutral | None | None | None | None | I |
| E/D | 0.1545 | likely_benign | 0.1538 | benign | -0.289 | Destabilizing | 0.999 | D | 0.541 | neutral | N | 0.518012734 | None | None | I |
| E/F | 0.7868 | likely_pathogenic | 0.7785 | pathogenic | -0.168 | Destabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | I |
| E/G | 0.3101 | likely_benign | 0.3089 | benign | -0.41 | Destabilizing | 1.0 | D | 0.675 | prob.neutral | N | 0.512207737 | None | None | I |
| E/H | 0.6284 | likely_pathogenic | 0.6238 | pathogenic | 0.146 | Stabilizing | 1.0 | D | 0.615 | neutral | None | None | None | None | I |
| E/I | 0.3438 | ambiguous | 0.3319 | benign | 0.183 | Stabilizing | 1.0 | D | 0.68 | prob.neutral | None | None | None | None | I |
| E/K | 0.2501 | likely_benign | 0.2503 | benign | 0.423 | Stabilizing | 0.999 | D | 0.699 | prob.neutral | N | 0.464679681 | None | None | I |
| E/L | 0.355 | ambiguous | 0.3576 | ambiguous | 0.183 | Stabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | I |
| E/M | 0.4628 | ambiguous | 0.4506 | ambiguous | 0.185 | Stabilizing | 1.0 | D | 0.633 | neutral | None | None | None | None | I |
| E/N | 0.3743 | ambiguous | 0.3574 | ambiguous | 0.138 | Stabilizing | 1.0 | D | 0.692 | prob.neutral | None | None | None | None | I |
| E/P | 0.4539 | ambiguous | 0.4413 | ambiguous | 0.063 | Stabilizing | 1.0 | D | 0.628 | neutral | None | None | None | None | I |
| E/Q | 0.1781 | likely_benign | 0.1749 | benign | 0.164 | Stabilizing | 1.0 | D | 0.622 | neutral | N | 0.496560026 | None | None | I |
| E/R | 0.3941 | ambiguous | 0.3896 | ambiguous | 0.612 | Stabilizing | 1.0 | D | 0.688 | prob.neutral | None | None | None | None | I |
| E/S | 0.2668 | likely_benign | 0.2538 | benign | -0.013 | Destabilizing | 0.999 | D | 0.692 | prob.neutral | None | None | None | None | I |
| E/T | 0.2916 | likely_benign | 0.2752 | benign | 0.132 | Stabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | I |
| E/V | 0.1988 | likely_benign | 0.1961 | benign | 0.063 | Stabilizing | 1.0 | D | 0.695 | prob.neutral | N | 0.506913093 | None | None | I |
| E/W | 0.9381 | likely_pathogenic | 0.9348 | pathogenic | -0.051 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | I |
| E/Y | 0.6781 | likely_pathogenic | 0.6698 | pathogenic | 0.074 | Stabilizing | 1.0 | D | 0.647 | 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.