Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31964 | 96115;96116;96117 | chr2:178544339;178544338;178544337 | chr2:179409066;179409065;179409064 |
| N2AB | 30323 | 91192;91193;91194 | chr2:178544339;178544338;178544337 | chr2:179409066;179409065;179409064 |
| N2A | 29396 | 88411;88412;88413 | chr2:178544339;178544338;178544337 | chr2:179409066;179409065;179409064 |
| N2B | 22899 | 68920;68921;68922 | chr2:178544339;178544338;178544337 | chr2:179409066;179409065;179409064 |
| Novex-1 | 23024 | 69295;69296;69297 | chr2:178544339;178544338;178544337 | chr2:179409066;179409065;179409064 |
| Novex-2 | 23091 | 69496;69497;69498 | chr2:178544339;178544338;178544337 | chr2:179409066;179409065;179409064 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs1354236675  |
-0.122 | 0.669 | N | 0.412 | 0.168 | 0.44307954383 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 1.14863E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/I | rs1354236675 |
-0.122 | 0.669 | N | 0.412 | 0.168 | 0.44307954383 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/I | rs1354236675 |
-0.122 | 0.669 | N | 0.412 | 0.168 | 0.44307954383 | gnomAD-4.0.0 | 6.57869E-06 | None | None | None | None | N | None | 2.41721E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/K | rs1354236675 |
None | 0.801 | N | 0.391 | 0.206 | 0.450928719235 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| T/K | rs1354236675 |
None | 0.801 | N | 0.391 | 0.206 | 0.450928719235 | gnomAD-4.0.0 | 2.47909E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.39059E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0807 | likely_benign | 0.0809 | benign | -0.853 | Destabilizing | 0.022 | N | 0.106 | neutral | N | 0.445256053 | None | None | N |
| T/C | 0.3377 | likely_benign | 0.3661 | ambiguous | -0.468 | Destabilizing | 0.998 | D | 0.422 | neutral | None | None | None | None | N |
| T/D | 0.5405 | ambiguous | 0.5441 | ambiguous | -0.261 | Destabilizing | 0.915 | D | 0.437 | neutral | None | None | None | None | N |
| T/E | 0.3918 | ambiguous | 0.4073 | ambiguous | -0.233 | Destabilizing | 0.915 | D | 0.402 | neutral | None | None | None | None | N |
| T/F | 0.2287 | likely_benign | 0.25 | benign | -0.77 | Destabilizing | 0.949 | D | 0.502 | neutral | None | None | None | None | N |
| T/G | 0.2823 | likely_benign | 0.2781 | benign | -1.15 | Destabilizing | 0.842 | D | 0.453 | neutral | None | None | None | None | N |
| T/H | 0.3252 | likely_benign | 0.3378 | benign | -1.386 | Destabilizing | 0.998 | D | 0.476 | neutral | None | None | None | None | N |
| T/I | 0.1387 | likely_benign | 0.1535 | benign | -0.143 | Destabilizing | 0.669 | D | 0.412 | neutral | N | 0.484062371 | None | None | N |
| T/K | 0.2793 | likely_benign | 0.2773 | benign | -0.786 | Destabilizing | 0.801 | D | 0.391 | neutral | N | 0.451123233 | None | None | N |
| T/L | 0.094 | likely_benign | 0.0928 | benign | -0.143 | Destabilizing | 0.275 | N | 0.393 | neutral | None | None | None | None | N |
| T/M | 0.0907 | likely_benign | 0.0917 | benign | 0.121 | Stabilizing | 0.325 | N | 0.285 | neutral | None | None | None | None | N |
| T/N | 0.1565 | likely_benign | 0.1579 | benign | -0.755 | Destabilizing | 0.991 | D | 0.433 | neutral | None | None | None | None | N |
| T/P | 0.1741 | likely_benign | 0.1759 | benign | -0.346 | Destabilizing | 0.005 | N | 0.181 | neutral | N | 0.407353813 | None | None | N |
| T/Q | 0.2746 | likely_benign | 0.2837 | benign | -0.853 | Destabilizing | 0.974 | D | 0.475 | neutral | None | None | None | None | N |
| T/R | 0.2431 | likely_benign | 0.2504 | benign | -0.61 | Destabilizing | 0.966 | D | 0.472 | neutral | N | 0.462975023 | None | None | N |
| T/S | 0.1296 | likely_benign | 0.1344 | benign | -1.048 | Destabilizing | 0.454 | N | 0.417 | neutral | N | 0.456566338 | None | None | N |
| T/V | 0.1022 | likely_benign | 0.1124 | benign | -0.346 | Destabilizing | 0.067 | N | 0.134 | neutral | None | None | None | None | N |
| T/W | 0.6497 | likely_pathogenic | 0.6752 | pathogenic | -0.721 | Destabilizing | 0.998 | D | 0.516 | neutral | None | None | None | None | N |
| T/Y | 0.272 | likely_benign | 0.2981 | benign | -0.497 | Destabilizing | 0.974 | D | 0.503 | 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.