Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25359 | 76300;76301;76302 | chr2:178570057;178570056;178570055 | chr2:179434784;179434783;179434782 |
| N2AB | 23718 | 71377;71378;71379 | chr2:178570057;178570056;178570055 | chr2:179434784;179434783;179434782 |
| N2A | 22791 | 68596;68597;68598 | chr2:178570057;178570056;178570055 | chr2:179434784;179434783;179434782 |
| N2B | 16294 | 49105;49106;49107 | chr2:178570057;178570056;178570055 | chr2:179434784;179434783;179434782 |
| Novex-1 | 16419 | 49480;49481;49482 | chr2:178570057;178570056;178570055 | chr2:179434784;179434783;179434782 |
| Novex-2 | 16486 | 49681;49682;49683 | chr2:178570057;178570056;178570055 | chr2:179434784;179434783;179434782 |
| 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/N | None | None | 0.99 | N | 0.707 | 0.4 | 0.83719327144 | gnomAD-4.0.0 | 6.84349E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99594E-07 | 0 | 0 |
| I/T | rs779076165  |
-2.226 | 0.822 | N | 0.497 | 0.253 | 0.584582053011 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 9.81E-05 | None | 0 | 0 | 0 |
| I/T | rs779076165 |
-2.226 | 0.822 | N | 0.497 | 0.253 | 0.584582053011 | gnomAD-4.0.0 | 4.1061E-06 | None | None | None | None | N | None | 0 | 2.23684E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 5.79737E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.2605 | likely_benign | 0.2306 | benign | -2.39 | Highly Destabilizing | 0.559 | D | 0.457 | neutral | None | None | None | None | N |
| I/C | 0.7521 | likely_pathogenic | 0.7497 | pathogenic | -1.4 | Destabilizing | 0.998 | D | 0.622 | neutral | None | None | None | None | N |
| I/D | 0.9656 | likely_pathogenic | 0.9449 | pathogenic | -2.603 | Highly Destabilizing | 0.993 | D | 0.681 | prob.neutral | None | None | None | None | N |
| I/E | 0.9166 | likely_pathogenic | 0.8838 | pathogenic | -2.364 | Highly Destabilizing | 0.978 | D | 0.649 | neutral | None | None | None | None | N |
| I/F | 0.3921 | ambiguous | 0.3322 | benign | -1.403 | Destabilizing | 0.942 | D | 0.56 | neutral | N | 0.481635453 | None | None | N |
| I/G | 0.7991 | likely_pathogenic | 0.7471 | pathogenic | -2.937 | Highly Destabilizing | 0.978 | D | 0.637 | neutral | None | None | None | None | N |
| I/H | 0.8768 | likely_pathogenic | 0.8312 | pathogenic | -2.356 | Highly Destabilizing | 0.998 | D | 0.703 | prob.neutral | None | None | None | None | N |
| I/K | 0.8915 | likely_pathogenic | 0.8521 | pathogenic | -1.76 | Destabilizing | 0.978 | D | 0.655 | neutral | None | None | None | None | N |
| I/L | 0.1105 | likely_benign | 0.1127 | benign | -0.806 | Destabilizing | 0.294 | N | 0.325 | neutral | N | 0.476786895 | None | None | N |
| I/M | 0.1558 | likely_benign | 0.1478 | benign | -0.631 | Destabilizing | 0.97 | D | 0.609 | neutral | N | 0.493156343 | None | None | N |
| I/N | 0.7088 | likely_pathogenic | 0.6415 | pathogenic | -2.1 | Highly Destabilizing | 0.99 | D | 0.707 | prob.neutral | N | 0.469933072 | None | None | N |
| I/P | 0.7659 | likely_pathogenic | 0.7053 | pathogenic | -1.316 | Destabilizing | 0.993 | D | 0.685 | prob.neutral | None | None | None | None | N |
| I/Q | 0.8203 | likely_pathogenic | 0.7832 | pathogenic | -1.948 | Destabilizing | 0.993 | D | 0.711 | prob.delet. | None | None | None | None | N |
| I/R | 0.8072 | likely_pathogenic | 0.7384 | pathogenic | -1.538 | Destabilizing | 0.978 | D | 0.71 | prob.delet. | None | None | None | None | N |
| I/S | 0.4619 | ambiguous | 0.4003 | ambiguous | -2.786 | Highly Destabilizing | 0.942 | D | 0.597 | neutral | N | 0.463171896 | None | None | N |
| I/T | 0.1586 | likely_benign | 0.1406 | benign | -2.4 | Highly Destabilizing | 0.822 | D | 0.497 | neutral | N | 0.519129376 | None | None | N |
| I/V | 0.0838 | likely_benign | 0.0851 | benign | -1.316 | Destabilizing | 0.002 | N | 0.181 | neutral | N | 0.413082133 | None | None | N |
| I/W | 0.9476 | likely_pathogenic | 0.9195 | pathogenic | -1.797 | Destabilizing | 0.998 | D | 0.716 | prob.delet. | None | None | None | None | N |
| I/Y | 0.879 | likely_pathogenic | 0.8264 | pathogenic | -1.472 | Destabilizing | 0.978 | D | 0.621 | 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.