Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1754 | 5485;5486;5487 | chr2:178776604;178776603;178776602 | chr2:179641331;179641330;179641329 |
| N2AB | 1754 | 5485;5486;5487 | chr2:178776604;178776603;178776602 | chr2:179641331;179641330;179641329 |
| N2A | 1754 | 5485;5486;5487 | chr2:178776604;178776603;178776602 | chr2:179641331;179641330;179641329 |
| N2B | 1708 | 5347;5348;5349 | chr2:178776604;178776603;178776602 | chr2:179641331;179641330;179641329 |
| Novex-1 | 1708 | 5347;5348;5349 | chr2:178776604;178776603;178776602 | chr2:179641331;179641330;179641329 |
| Novex-2 | 1708 | 5347;5348;5349 | chr2:178776604;178776603;178776602 | chr2:179641331;179641330;179641329 |
| Novex-3 | 1754 | 5485;5486;5487 | chr2:178776604;178776603;178776602 | chr2:179641331;179641330;179641329 |
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/F | rs780379544  |
-0.757 | 0.984 | N | 0.437 | 0.351 | 0.513674172182 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| I/F | rs780379544 |
-0.757 | 0.984 | N | 0.437 | 0.351 | 0.513674172182 | gnomAD-4.0.0 | 6.84116E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15931E-05 | 0 |
| I/N | None | None | 0.995 | N | 0.603 | 0.568 | 0.848516524615 | gnomAD-4.0.0 | 1.59077E-06 | None | None | None | None | I | None | 0 | 2.28686E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs780379544 |
-0.226 | 0.004 | N | 0.103 | 0.212 | 0.525258673147 | gnomAD-2.1.1 | 7.98E-06 | None | None | None | None | I | None | 0 | 2.89E-05 | None | 0 | 0 | None | 0 | None | 0 | 8.83E-06 | 0 |
| I/V | rs780379544 |
-0.226 | 0.004 | N | 0.103 | 0.212 | 0.525258673147 | gnomAD-4.0.0 | 2.05235E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69789E-06 | 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 | 0.6858 | likely_pathogenic | 0.6755 | pathogenic | -1.682 | Destabilizing | 0.702 | D | 0.413 | neutral | None | None | None | None | I |
| I/C | 0.9133 | likely_pathogenic | 0.9287 | pathogenic | -0.737 | Destabilizing | 0.999 | D | 0.526 | neutral | None | None | None | None | I |
| I/D | 0.9332 | likely_pathogenic | 0.9318 | pathogenic | -1.298 | Destabilizing | 0.996 | D | 0.605 | neutral | None | None | None | None | I |
| I/E | 0.8338 | likely_pathogenic | 0.8119 | pathogenic | -1.309 | Destabilizing | 0.988 | D | 0.583 | neutral | None | None | None | None | I |
| I/F | 0.4025 | ambiguous | 0.4128 | ambiguous | -1.252 | Destabilizing | 0.984 | D | 0.437 | neutral | N | 0.50121464 | None | None | I |
| I/G | 0.9103 | likely_pathogenic | 0.9049 | pathogenic | -1.999 | Destabilizing | 0.988 | D | 0.541 | neutral | None | None | None | None | I |
| I/H | 0.8112 | likely_pathogenic | 0.8133 | pathogenic | -1.301 | Destabilizing | 0.999 | D | 0.598 | neutral | None | None | None | None | I |
| I/K | 0.6982 | likely_pathogenic | 0.7032 | pathogenic | -1.083 | Destabilizing | 0.988 | D | 0.591 | neutral | None | None | None | None | I |
| I/L | 0.217 | likely_benign | 0.2175 | benign | -0.882 | Destabilizing | 0.437 | N | 0.181 | neutral | N | 0.439375313 | None | None | I |
| I/M | 0.176 | likely_benign | 0.18 | benign | -0.52 | Destabilizing | 0.984 | D | 0.499 | neutral | N | 0.429412314 | None | None | I |
| I/N | 0.5409 | ambiguous | 0.5433 | ambiguous | -0.798 | Destabilizing | 0.995 | D | 0.603 | neutral | N | 0.506836666 | None | None | I |
| I/P | 0.981 | likely_pathogenic | 0.9832 | pathogenic | -1.118 | Destabilizing | 0.996 | D | 0.607 | neutral | None | None | None | None | I |
| I/Q | 0.6967 | likely_pathogenic | 0.6789 | pathogenic | -1.013 | Destabilizing | 0.996 | D | 0.612 | neutral | None | None | None | None | I |
| I/R | 0.6291 | likely_pathogenic | 0.6193 | pathogenic | -0.464 | Destabilizing | 0.996 | D | 0.607 | neutral | None | None | None | None | I |
| I/S | 0.629 | likely_pathogenic | 0.6347 | pathogenic | -1.353 | Destabilizing | 0.984 | D | 0.497 | neutral | N | 0.478358811 | None | None | I |
| I/T | 0.4015 | ambiguous | 0.4215 | ambiguous | -1.257 | Destabilizing | 0.896 | D | 0.428 | neutral | N | 0.421962001 | None | None | I |
| I/V | 0.0937 | likely_benign | 0.0932 | benign | -1.118 | Destabilizing | 0.004 | N | 0.103 | neutral | N | 0.43093337 | None | None | I |
| I/W | 0.9376 | likely_pathogenic | 0.9377 | pathogenic | -1.352 | Destabilizing | 0.999 | D | 0.669 | neutral | None | None | None | None | I |
| I/Y | 0.8049 | likely_pathogenic | 0.8086 | pathogenic | -1.14 | Destabilizing | 0.996 | D | 0.526 | 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.