Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23317 | 70174;70175;70176 | chr2:178576183;178576182;178576181 | chr2:179440910;179440909;179440908 |
| N2AB | 21676 | 65251;65252;65253 | chr2:178576183;178576182;178576181 | chr2:179440910;179440909;179440908 |
| N2A | 20749 | 62470;62471;62472 | chr2:178576183;178576182;178576181 | chr2:179440910;179440909;179440908 |
| N2B | 14252 | 42979;42980;42981 | chr2:178576183;178576182;178576181 | chr2:179440910;179440909;179440908 |
| Novex-1 | 14377 | 43354;43355;43356 | chr2:178576183;178576182;178576181 | chr2:179440910;179440909;179440908 |
| Novex-2 | 14444 | 43555;43556;43557 | chr2:178576183;178576182;178576181 | chr2:179440910;179440909;179440908 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/R | rs1165001201  |
-0.801 | None | N | 0.456 | 0.328 | 0.137902524267 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.28E-05 | None | 0 | 0 | 0 |
| S/R | rs1165001201 |
-0.801 | None | N | 0.456 | 0.328 | 0.137902524267 | gnomAD-4.0.0 | 3.18633E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.87026E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0962 | likely_benign | 0.0977 | benign | -0.903 | Destabilizing | 0.007 | N | 0.432 | neutral | None | None | None | None | N |
| S/C | 0.0442 | likely_benign | 0.0394 | benign | -0.846 | Destabilizing | None | N | 0.493 | neutral | N | 0.505128289 | None | None | N |
| S/D | 0.8037 | likely_pathogenic | 0.7853 | pathogenic | -1.889 | Destabilizing | 0.072 | N | 0.603 | neutral | None | None | None | None | N |
| S/E | 0.7377 | likely_pathogenic | 0.6938 | pathogenic | -1.675 | Destabilizing | 0.038 | N | 0.597 | neutral | None | None | None | None | N |
| S/F | 0.223 | likely_benign | 0.2408 | benign | -0.504 | Destabilizing | None | N | 0.673 | neutral | None | None | None | None | N |
| S/G | 0.1416 | likely_benign | 0.1353 | benign | -1.299 | Destabilizing | 0.024 | N | 0.541 | neutral | N | 0.485687604 | None | None | N |
| S/H | 0.3668 | ambiguous | 0.295 | benign | -1.609 | Destabilizing | 0.356 | N | 0.719 | prob.delet. | None | None | None | None | N |
| S/I | 0.2384 | likely_benign | 0.2257 | benign | 0.113 | Stabilizing | None | N | 0.566 | neutral | N | 0.489542761 | None | None | N |
| S/K | 0.6683 | likely_pathogenic | 0.5614 | ambiguous | -0.634 | Destabilizing | 0.016 | N | 0.541 | neutral | None | None | None | None | N |
| S/L | 0.1293 | likely_benign | 0.1364 | benign | 0.113 | Stabilizing | None | N | 0.51 | neutral | None | None | None | None | N |
| S/M | 0.1741 | likely_benign | 0.174 | benign | -0.155 | Destabilizing | 0.214 | N | 0.719 | prob.delet. | None | None | None | None | N |
| S/N | 0.3078 | likely_benign | 0.3007 | benign | -1.367 | Destabilizing | 0.055 | N | 0.6 | neutral | N | 0.485180625 | None | None | N |
| S/P | 0.9792 | likely_pathogenic | 0.9796 | pathogenic | -0.193 | Destabilizing | 0.356 | N | 0.73 | prob.delet. | None | None | None | None | N |
| S/Q | 0.4935 | ambiguous | 0.4 | ambiguous | -1.019 | Destabilizing | 0.12 | N | 0.658 | neutral | None | None | None | None | N |
| S/R | 0.4914 | ambiguous | 0.3678 | ambiguous | -1.038 | Destabilizing | None | N | 0.456 | neutral | N | 0.407886957 | None | None | N |
| S/T | 0.1002 | likely_benign | 0.1064 | benign | -0.961 | Destabilizing | 0.001 | N | 0.253 | neutral | N | 0.473226515 | None | None | N |
| S/V | 0.2245 | likely_benign | 0.2283 | benign | -0.193 | Destabilizing | 0.016 | N | 0.704 | prob.neutral | None | None | None | None | N |
| S/W | 0.3539 | ambiguous | 0.3277 | benign | -0.895 | Destabilizing | 0.676 | D | 0.726 | prob.delet. | None | None | None | None | N |
| S/Y | 0.2102 | likely_benign | 0.2023 | benign | -0.442 | Destabilizing | 0.12 | N | 0.731 | prob.delet. | 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.