Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26196 | 78811;78812;78813 | chr2:178567546;178567545;178567544 | chr2:179432273;179432272;179432271 |
| N2AB | 24555 | 73888;73889;73890 | chr2:178567546;178567545;178567544 | chr2:179432273;179432272;179432271 |
| N2A | 23628 | 71107;71108;71109 | chr2:178567546;178567545;178567544 | chr2:179432273;179432272;179432271 |
| N2B | 17131 | 51616;51617;51618 | chr2:178567546;178567545;178567544 | chr2:179432273;179432272;179432271 |
| Novex-1 | 17256 | 51991;51992;51993 | chr2:178567546;178567545;178567544 | chr2:179432273;179432272;179432271 |
| Novex-2 | 17323 | 52192;52193;52194 | chr2:178567546;178567545;178567544 | chr2:179432273;179432272;179432271 |
| 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/E | None | None | 0.9 | N | 0.428 | 0.155 | 0.215109475489 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| D/G | None | None | 0.956 | N | 0.465 | 0.41 | 0.327419511103 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| D/H | rs777065318  |
None | 0.999 | D | 0.537 | 0.441 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/H | rs777065318 |
None | 0.999 | D | 0.537 | 0.441 | None | gnomAD-4.0.0 | 1.49085E-05 | None | None | None | None | I | None | 1.33733E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.95251E-05 | 0 | 0 |
| D/N | rs777065318 |
0.065 | 0.997 | N | 0.491 | 0.354 | 0.335414705075 | gnomAD-2.1.1 | 4.08E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.38E-05 | None | 0 | 0 | 0 |
| D/N | rs777065318 |
0.065 | 0.997 | N | 0.491 | 0.354 | 0.335414705075 | gnomAD-4.0.0 | 6.85989E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.17028E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.5931 | likely_pathogenic | 0.5771 | pathogenic | -0.271 | Destabilizing | 0.37 | N | 0.322 | neutral | D | 0.529995022 | None | None | I |
| D/C | 0.9436 | likely_pathogenic | 0.9349 | pathogenic | -0.265 | Destabilizing | 1.0 | D | 0.675 | prob.neutral | None | None | None | None | I |
| D/E | 0.6074 | likely_pathogenic | 0.5928 | pathogenic | -0.461 | Destabilizing | 0.9 | D | 0.428 | neutral | N | 0.503424497 | None | None | I |
| D/F | 0.9374 | likely_pathogenic | 0.9286 | pathogenic | 0.093 | Stabilizing | 0.999 | D | 0.688 | prob.neutral | None | None | None | None | I |
| D/G | 0.7654 | likely_pathogenic | 0.7586 | pathogenic | -0.525 | Destabilizing | 0.956 | D | 0.465 | neutral | N | 0.514024027 | None | None | I |
| D/H | 0.7446 | likely_pathogenic | 0.7382 | pathogenic | 0.382 | Stabilizing | 0.999 | D | 0.537 | neutral | D | 0.525887311 | None | None | I |
| D/I | 0.8708 | likely_pathogenic | 0.8546 | pathogenic | 0.366 | Stabilizing | 0.998 | D | 0.68 | prob.neutral | None | None | None | None | I |
| D/K | 0.9325 | likely_pathogenic | 0.9284 | pathogenic | 0.105 | Stabilizing | 0.967 | D | 0.505 | neutral | None | None | None | None | I |
| D/L | 0.7708 | likely_pathogenic | 0.7543 | pathogenic | 0.366 | Stabilizing | 0.995 | D | 0.698 | prob.neutral | None | None | None | None | I |
| D/M | 0.9517 | likely_pathogenic | 0.9408 | pathogenic | 0.325 | Stabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | I |
| D/N | 0.3998 | ambiguous | 0.406 | ambiguous | -0.421 | Destabilizing | 0.997 | D | 0.491 | neutral | N | 0.490639853 | None | None | I |
| D/P | 0.8369 | likely_pathogenic | 0.8131 | pathogenic | 0.177 | Stabilizing | 0.998 | D | 0.553 | neutral | None | None | None | None | I |
| D/Q | 0.8937 | likely_pathogenic | 0.8869 | pathogenic | -0.332 | Destabilizing | 0.84 | D | 0.279 | neutral | None | None | None | None | I |
| D/R | 0.9466 | likely_pathogenic | 0.9435 | pathogenic | 0.472 | Stabilizing | 0.995 | D | 0.643 | neutral | None | None | None | None | I |
| D/S | 0.5181 | ambiguous | 0.5228 | ambiguous | -0.526 | Destabilizing | 0.967 | D | 0.441 | neutral | None | None | None | None | I |
| D/T | 0.8527 | likely_pathogenic | 0.8408 | pathogenic | -0.316 | Destabilizing | 0.995 | D | 0.515 | neutral | None | None | None | None | I |
| D/V | 0.7362 | likely_pathogenic | 0.7087 | pathogenic | 0.177 | Stabilizing | 0.994 | D | 0.698 | prob.neutral | N | 0.495666282 | None | None | I |
| D/W | 0.9885 | likely_pathogenic | 0.9855 | pathogenic | 0.285 | Stabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | I |
| D/Y | 0.6287 | likely_pathogenic | 0.6158 | pathogenic | 0.349 | Stabilizing | 0.999 | D | 0.686 | prob.neutral | D | 0.526140801 | 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.