Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23919 | 71980;71981;71982 | chr2:178574377;178574376;178574375 | chr2:179439104;179439103;179439102 |
| N2AB | 22278 | 67057;67058;67059 | chr2:178574377;178574376;178574375 | chr2:179439104;179439103;179439102 |
| N2A | 21351 | 64276;64277;64278 | chr2:178574377;178574376;178574375 | chr2:179439104;179439103;179439102 |
| N2B | 14854 | 44785;44786;44787 | chr2:178574377;178574376;178574375 | chr2:179439104;179439103;179439102 |
| Novex-1 | 14979 | 45160;45161;45162 | chr2:178574377;178574376;178574375 | chr2:179439104;179439103;179439102 |
| Novex-2 | 15046 | 45361;45362;45363 | chr2:178574377;178574376;178574375 | chr2:179439104;179439103;179439102 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/R | rs769164762  |
-1.076 | 0.026 | N | 0.632 | 0.049 | 0.257292322809 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| M/T | None | None | None | N | 0.355 | 0.075 | 0.36893422563 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-06 | 0 | 0 |
| M/V | rs777077373 |
-1.092 | None | N | 0.121 | 0.103 | 0.0762999501168 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 9.95E-05 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| M/V | rs777077373 |
-1.092 | None | N | 0.121 | 0.103 | 0.0762999501168 | gnomAD-4.0.0 | 3.42137E-06 | None | None | None | None | N | None | 0 | 2.23634E-05 | None | 0 | 2.52054E-05 | None | 0 | 0 | 1.79909E-06 | 0 | 1.65667E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.1073 | likely_benign | 0.1309 | benign | -1.542 | Destabilizing | 0.003 | N | 0.455 | neutral | None | None | None | None | N |
| M/C | 0.3721 | ambiguous | 0.4001 | ambiguous | -1.023 | Destabilizing | 0.204 | N | 0.499 | neutral | None | None | None | None | N |
| M/D | 0.5198 | ambiguous | 0.5679 | pathogenic | -0.519 | Destabilizing | 0.035 | N | 0.703 | prob.delet. | None | None | None | None | N |
| M/E | 0.2327 | likely_benign | 0.2589 | benign | -0.49 | Destabilizing | 0.035 | N | 0.559 | neutral | None | None | None | None | N |
| M/F | 0.1495 | likely_benign | 0.1674 | benign | -0.652 | Destabilizing | 0.035 | N | 0.451 | neutral | None | None | None | None | N |
| M/G | 0.2569 | likely_benign | 0.3086 | benign | -1.824 | Destabilizing | 0.035 | N | 0.579 | neutral | None | None | None | None | N |
| M/H | 0.2351 | likely_benign | 0.272 | benign | -0.799 | Destabilizing | 0.439 | N | 0.57 | neutral | None | None | None | None | N |
| M/I | 0.0999 | likely_benign | 0.1041 | benign | -0.821 | Destabilizing | None | N | 0.167 | neutral | N | 0.372251444 | None | None | N |
| M/K | 0.1057 | likely_benign | 0.118 | benign | -0.528 | Destabilizing | 0.026 | N | 0.547 | neutral | N | 0.477186753 | None | None | N |
| M/L | 0.0759 | likely_benign | 0.0825 | benign | -0.821 | Destabilizing | None | N | 0.183 | neutral | N | 0.402054276 | None | None | N |
| M/N | 0.2204 | likely_benign | 0.2578 | benign | -0.439 | Destabilizing | 0.035 | N | 0.664 | prob.neutral | None | None | None | None | N |
| M/P | 0.7984 | likely_pathogenic | 0.8408 | pathogenic | -1.037 | Destabilizing | 0.068 | N | 0.657 | prob.neutral | None | None | None | None | N |
| M/Q | 0.121 | likely_benign | 0.1337 | benign | -0.509 | Destabilizing | 0.068 | N | 0.494 | neutral | None | None | None | None | N |
| M/R | 0.1032 | likely_benign | 0.1152 | benign | 0.001 | Stabilizing | 0.026 | N | 0.632 | neutral | N | 0.475973244 | None | None | N |
| M/S | 0.1377 | likely_benign | 0.1663 | benign | -0.974 | Destabilizing | 0.007 | N | 0.479 | neutral | None | None | None | None | N |
| M/T | 0.0709 | likely_benign | 0.0756 | benign | -0.835 | Destabilizing | None | N | 0.355 | neutral | N | 0.426371143 | None | None | N |
| M/V | 0.0512 | likely_benign | 0.0506 | benign | -1.037 | Destabilizing | None | N | 0.121 | neutral | N | 0.360052938 | None | None | N |
| M/W | 0.484 | ambiguous | 0.5558 | ambiguous | -0.587 | Destabilizing | 0.747 | D | 0.503 | neutral | None | None | None | None | N |
| M/Y | 0.3073 | likely_benign | 0.3566 | ambiguous | -0.602 | Destabilizing | 0.068 | N | 0.637 | 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.