Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30715 | 92368;92369;92370 | chr2:178549579;178549578;178549577 | chr2:179414306;179414305;179414304 |
| N2AB | 29074 | 87445;87446;87447 | chr2:178549579;178549578;178549577 | chr2:179414306;179414305;179414304 |
| N2A | 28147 | 84664;84665;84666 | chr2:178549579;178549578;178549577 | chr2:179414306;179414305;179414304 |
| N2B | 21650 | 65173;65174;65175 | chr2:178549579;178549578;178549577 | chr2:179414306;179414305;179414304 |
| Novex-1 | 21775 | 65548;65549;65550 | chr2:178549579;178549578;178549577 | chr2:179414306;179414305;179414304 |
| Novex-2 | 21842 | 65749;65750;65751 | chr2:178549579;178549578;178549577 | chr2:179414306;179414305;179414304 |
| 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/M | rs767562959  |
-0.485 | 0.068 | N | 0.269 | 0.046 | 0.376216005999 | gnomAD-2.1.1 | 1.8E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.56279E-04 | None | 0 | None | 0 | 0 | 0 |
| I/M | rs767562959 |
-0.485 | 0.068 | N | 0.269 | 0.046 | 0.376216005999 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 3.84615E-04 | None | 0 | 0 | 0 | 0 | 0 |
| I/M | rs767562959 |
-0.485 | 0.068 | N | 0.269 | 0.046 | 0.376216005999 | gnomAD-4.0.0 | 4.34188E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.33738E-04 | None | 0 | 0 | 0 | 0 | 1.60251E-05 |
| I/T | None | None | 0.651 | N | 0.422 | 0.222 | 0.416454006429 | gnomAD-4.0.0 | 1.59504E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77531E-05 | None | 0 | 0 | 0 | 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 | 0.3987 | ambiguous | 0.3741 | ambiguous | -0.441 | Destabilizing | 0.505 | D | 0.377 | neutral | None | None | None | None | N |
| I/C | 0.7336 | likely_pathogenic | 0.701 | pathogenic | -0.678 | Destabilizing | 0.995 | D | 0.273 | neutral | None | None | None | None | N |
| I/D | 0.6574 | likely_pathogenic | 0.6151 | pathogenic | -0.105 | Destabilizing | 0.946 | D | 0.498 | neutral | None | None | None | None | N |
| I/E | 0.5668 | likely_pathogenic | 0.5212 | ambiguous | -0.211 | Destabilizing | 0.897 | D | 0.507 | neutral | None | None | None | None | N |
| I/F | 0.1514 | likely_benign | 0.17 | benign | -0.584 | Destabilizing | 0.897 | D | 0.214 | neutral | None | None | None | None | N |
| I/G | 0.6596 | likely_pathogenic | 0.6511 | pathogenic | -0.558 | Destabilizing | 0.712 | D | 0.487 | neutral | None | None | None | None | N |
| I/H | 0.4695 | ambiguous | 0.4447 | ambiguous | 0.09 | Stabilizing | 0.995 | D | 0.315 | neutral | None | None | None | None | N |
| I/K | 0.3569 | ambiguous | 0.3272 | benign | -0.221 | Destabilizing | 0.651 | D | 0.493 | neutral | N | 0.423912415 | None | None | N |
| I/L | 0.1013 | likely_benign | 0.109 | benign | -0.267 | Destabilizing | 0.002 | N | 0.108 | neutral | N | 0.391895997 | None | None | N |
| I/M | 0.0875 | likely_benign | 0.0937 | benign | -0.399 | Destabilizing | 0.068 | N | 0.269 | neutral | N | 0.398958043 | None | None | N |
| I/N | 0.2243 | likely_benign | 0.194 | benign | -0.057 | Destabilizing | 0.946 | D | 0.473 | neutral | None | None | None | None | N |
| I/P | 0.5473 | ambiguous | 0.5253 | ambiguous | -0.294 | Destabilizing | 0.008 | N | 0.227 | neutral | None | None | None | None | N |
| I/Q | 0.3855 | ambiguous | 0.3735 | ambiguous | -0.284 | Destabilizing | 0.946 | D | 0.471 | neutral | None | None | None | None | N |
| I/R | 0.3044 | likely_benign | 0.2885 | benign | 0.296 | Stabilizing | 0.93 | D | 0.486 | neutral | N | 0.423739057 | None | None | N |
| I/S | 0.3131 | likely_benign | 0.2859 | benign | -0.474 | Destabilizing | 0.712 | D | 0.36 | neutral | None | None | None | None | N |
| I/T | 0.3422 | ambiguous | 0.3039 | benign | -0.476 | Destabilizing | 0.651 | D | 0.422 | neutral | N | 0.350227441 | None | None | N |
| I/V | 0.1052 | likely_benign | 0.1043 | benign | -0.294 | Destabilizing | 0.144 | N | 0.261 | neutral | N | 0.427894083 | None | None | N |
| I/W | 0.7155 | likely_pathogenic | 0.753 | pathogenic | -0.591 | Destabilizing | 0.995 | D | 0.389 | neutral | None | None | None | None | N |
| I/Y | 0.4482 | ambiguous | 0.4255 | ambiguous | -0.333 | Destabilizing | 0.982 | D | 0.359 | 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.