Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32908 | 98947;98948;98949 | chr2:178539213;178539212;178539211 | chr2:179403940;179403939;179403938 |
| N2AB | 31267 | 94024;94025;94026 | chr2:178539213;178539212;178539211 | chr2:179403940;179403939;179403938 |
| N2A | 30340 | 91243;91244;91245 | chr2:178539213;178539212;178539211 | chr2:179403940;179403939;179403938 |
| N2B | 23843 | 71752;71753;71754 | chr2:178539213;178539212;178539211 | chr2:179403940;179403939;179403938 |
| Novex-1 | 23968 | 72127;72128;72129 | chr2:178539213;178539212;178539211 | chr2:179403940;179403939;179403938 |
| Novex-2 | 24035 | 72328;72329;72330 | chr2:178539213;178539212;178539211 | chr2:179403940;179403939;179403938 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/H | None | None | 1.0 | N | 0.608 | 0.469 | 0.387366425376 | gnomAD-4.0.0 | 6.84248E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65684E-05 |
| D/N | rs267599023  |
0.419 | 1.0 | N | 0.611 | 0.376 | 0.321108458156 | 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 |
| D/N | rs267599023 |
0.419 | 1.0 | N | 0.611 | 0.376 | 0.321108458156 | gnomAD-4.0.0 | 9.57947E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.39712E-06 | 6.95652E-05 | 3.31367E-05 |
| D/Y | None | None | 1.0 | N | 0.645 | 0.482 | 0.736162974464 | gnomAD-4.0.0 | 6.84248E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.9952E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.6383 | likely_pathogenic | 0.6787 | pathogenic | -0.229 | Destabilizing | 1.0 | D | 0.686 | prob.neutral | N | 0.467405539 | None | None | N |
| D/C | 0.9484 | likely_pathogenic | 0.9542 | pathogenic | -0.018 | Destabilizing | 1.0 | D | 0.656 | neutral | None | None | None | None | N |
| D/E | 0.4264 | ambiguous | 0.4447 | ambiguous | -0.226 | Destabilizing | 1.0 | D | 0.381 | neutral | N | 0.465857825 | None | None | N |
| D/F | 0.9298 | likely_pathogenic | 0.9417 | pathogenic | -0.031 | Destabilizing | 1.0 | D | 0.665 | neutral | None | None | None | None | N |
| D/G | 0.6421 | likely_pathogenic | 0.7048 | pathogenic | -0.441 | Destabilizing | 1.0 | D | 0.682 | prob.neutral | N | 0.483561237 | None | None | N |
| D/H | 0.8194 | likely_pathogenic | 0.8535 | pathogenic | 0.168 | Stabilizing | 1.0 | D | 0.608 | neutral | N | 0.481803718 | None | None | N |
| D/I | 0.9136 | likely_pathogenic | 0.9324 | pathogenic | 0.284 | Stabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | N |
| D/K | 0.9286 | likely_pathogenic | 0.9443 | pathogenic | 0.405 | Stabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | N |
| D/L | 0.8536 | likely_pathogenic | 0.8655 | pathogenic | 0.284 | Stabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | N |
| D/M | 0.9463 | likely_pathogenic | 0.9514 | pathogenic | 0.337 | Stabilizing | 1.0 | D | 0.652 | neutral | None | None | None | None | N |
| D/N | 0.3982 | ambiguous | 0.462 | ambiguous | -0.038 | Destabilizing | 1.0 | D | 0.611 | neutral | N | 0.502914704 | None | None | N |
| D/P | 0.9922 | likely_pathogenic | 0.996 | pathogenic | 0.136 | Stabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| D/Q | 0.8466 | likely_pathogenic | 0.865 | pathogenic | 0.027 | Stabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | N |
| D/R | 0.9198 | likely_pathogenic | 0.9336 | pathogenic | 0.591 | Stabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | N |
| D/S | 0.4904 | ambiguous | 0.5568 | ambiguous | -0.125 | Destabilizing | 1.0 | D | 0.64 | neutral | None | None | None | None | N |
| D/T | 0.7665 | likely_pathogenic | 0.7971 | pathogenic | 0.052 | Stabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | N |
| D/V | 0.7715 | likely_pathogenic | 0.8132 | pathogenic | 0.136 | Stabilizing | 1.0 | D | 0.719 | prob.delet. | N | 0.48728422 | None | None | N |
| D/W | 0.9852 | likely_pathogenic | 0.9867 | pathogenic | 0.134 | Stabilizing | 1.0 | D | 0.653 | neutral | None | None | None | None | N |
| D/Y | 0.7171 | likely_pathogenic | 0.7611 | pathogenic | 0.22 | Stabilizing | 1.0 | D | 0.645 | neutral | N | 0.503693408 | 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.