Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26255 | 78988;78989;78990 | chr2:178567369;178567368;178567367 | chr2:179432096;179432095;179432094 |
| N2AB | 24614 | 74065;74066;74067 | chr2:178567369;178567368;178567367 | chr2:179432096;179432095;179432094 |
| N2A | 23687 | 71284;71285;71286 | chr2:178567369;178567368;178567367 | chr2:179432096;179432095;179432094 |
| N2B | 17190 | 51793;51794;51795 | chr2:178567369;178567368;178567367 | chr2:179432096;179432095;179432094 |
| Novex-1 | 17315 | 52168;52169;52170 | chr2:178567369;178567368;178567367 | chr2:179432096;179432095;179432094 |
| Novex-2 | 17382 | 52369;52370;52371 | chr2:178567369;178567368;178567367 | chr2:179432096;179432095;179432094 |
| 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 | 0.999 | N | 0.666 | 0.447 | 0.248417906384 | gnomAD-4.0.0 | 1.38675E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.81081E-06 | 0 | 0 |
| D/N | rs1368108260  |
0.2 | 0.993 | N | 0.684 | 0.355 | 0.184867976434 | gnomAD-2.1.1 | 8.7E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.88E-05 | 0 |
| D/N | rs1368108260 |
0.2 | 0.993 | N | 0.684 | 0.355 | 0.184867976434 | gnomAD-4.0.0 | 1.38675E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.81081E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.7144 | likely_pathogenic | 0.6988 | pathogenic | -0.462 | Destabilizing | 0.993 | D | 0.621 | neutral | N | 0.454579705 | None | None | I |
| D/C | 0.9593 | likely_pathogenic | 0.9522 | pathogenic | -0.012 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | I |
| D/E | 0.3684 | ambiguous | 0.3202 | benign | -0.471 | Destabilizing | 0.117 | N | 0.355 | neutral | N | 0.437777429 | None | None | I |
| D/F | 0.9454 | likely_pathogenic | 0.9332 | pathogenic | -0.443 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | I |
| D/G | 0.5659 | likely_pathogenic | 0.5482 | ambiguous | -0.696 | Destabilizing | 0.989 | D | 0.65 | neutral | N | 0.50277027 | None | None | I |
| D/H | 0.8266 | likely_pathogenic | 0.8238 | pathogenic | -0.549 | Destabilizing | 0.999 | D | 0.666 | neutral | N | 0.457808936 | None | None | I |
| D/I | 0.9513 | likely_pathogenic | 0.9415 | pathogenic | 0.115 | Stabilizing | 0.998 | D | 0.735 | prob.delet. | None | None | None | None | I |
| D/K | 0.9059 | likely_pathogenic | 0.9014 | pathogenic | 0.033 | Stabilizing | 0.99 | D | 0.65 | neutral | None | None | None | None | I |
| D/L | 0.9201 | likely_pathogenic | 0.9098 | pathogenic | 0.115 | Stabilizing | 0.995 | D | 0.712 | prob.delet. | None | None | None | None | I |
| D/M | 0.9602 | likely_pathogenic | 0.9533 | pathogenic | 0.436 | Stabilizing | 1.0 | D | 0.728 | prob.delet. | None | None | None | None | I |
| D/N | 0.3684 | ambiguous | 0.3512 | ambiguous | -0.231 | Destabilizing | 0.993 | D | 0.684 | prob.neutral | N | 0.464555811 | None | None | I |
| D/P | 0.9897 | likely_pathogenic | 0.9892 | pathogenic | -0.055 | Destabilizing | 0.998 | D | 0.676 | prob.neutral | None | None | None | None | I |
| D/Q | 0.8485 | likely_pathogenic | 0.8422 | pathogenic | -0.196 | Destabilizing | 0.99 | D | 0.704 | prob.neutral | None | None | None | None | I |
| D/R | 0.9231 | likely_pathogenic | 0.9225 | pathogenic | 0.136 | Stabilizing | 0.995 | D | 0.704 | prob.neutral | None | None | None | None | I |
| D/S | 0.5846 | likely_pathogenic | 0.5663 | pathogenic | -0.379 | Destabilizing | 0.983 | D | 0.654 | neutral | None | None | None | None | I |
| D/T | 0.8341 | likely_pathogenic | 0.8264 | pathogenic | -0.201 | Destabilizing | 0.995 | D | 0.683 | prob.neutral | None | None | None | None | I |
| D/V | 0.8346 | likely_pathogenic | 0.812 | pathogenic | -0.055 | Destabilizing | 0.997 | D | 0.711 | prob.delet. | N | 0.474774328 | None | None | I |
| D/W | 0.9823 | likely_pathogenic | 0.9808 | pathogenic | -0.317 | Destabilizing | 1.0 | D | 0.752 | deleterious | None | None | None | None | I |
| D/Y | 0.622 | likely_pathogenic | 0.5924 | pathogenic | -0.219 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | N | 0.470406235 | 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.