Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25168 | 75727;75728;75729 | chr2:178570630;178570629;178570628 | chr2:179435357;179435356;179435355 |
| N2AB | 23527 | 70804;70805;70806 | chr2:178570630;178570629;178570628 | chr2:179435357;179435356;179435355 |
| N2A | 22600 | 68023;68024;68025 | chr2:178570630;178570629;178570628 | chr2:179435357;179435356;179435355 |
| N2B | 16103 | 48532;48533;48534 | chr2:178570630;178570629;178570628 | chr2:179435357;179435356;179435355 |
| Novex-1 | 16228 | 48907;48908;48909 | chr2:178570630;178570629;178570628 | chr2:179435357;179435356;179435355 |
| Novex-2 | 16295 | 49108;49109;49110 | chr2:178570630;178570629;178570628 | chr2:179435357;179435356;179435355 |
| 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 | rs938587020  |
-0.413 | 0.001 | N | 0.393 | 0.384 | 0.26547132957 | gnomAD-2.1.1 | 9.29E-05 | None | None | None | None | N | None | 9.50649E-04 | 8.49E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/R | rs938587020 |
-0.413 | 0.001 | N | 0.393 | 0.384 | 0.26547132957 | gnomAD-3.1.2 | 2.95932E-04 | None | None | None | None | N | None | 1.01415E-03 | 1.9667E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/R | rs938587020 |
-0.413 | 0.001 | N | 0.393 | 0.384 | 0.26547132957 | 1000 genomes | 5.99042E-04 | None | None | None | None | N | None | 2.3E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| S/R | rs938587020 |
-0.413 | 0.001 | N | 0.393 | 0.384 | 0.26547132957 | gnomAD-4.0.0 | 4.77572E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 5.64823E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0745 | likely_benign | 0.0781 | benign | -0.929 | Destabilizing | 0.054 | N | 0.353 | neutral | None | None | None | None | N |
| S/C | 0.0746 | likely_benign | 0.0798 | benign | -0.898 | Destabilizing | 0.001 | N | 0.322 | neutral | N | 0.497178889 | None | None | N |
| S/D | 0.4663 | ambiguous | 0.5101 | ambiguous | -1.581 | Destabilizing | 0.563 | D | 0.551 | neutral | None | None | None | None | N |
| S/E | 0.4525 | ambiguous | 0.4914 | ambiguous | -1.415 | Destabilizing | 0.388 | N | 0.494 | neutral | None | None | None | None | N |
| S/F | 0.1118 | likely_benign | 0.1204 | benign | -0.929 | Destabilizing | 0.818 | D | 0.607 | neutral | None | None | None | None | N |
| S/G | 0.1151 | likely_benign | 0.1269 | benign | -1.297 | Destabilizing | 0.165 | N | 0.439 | neutral | D | 0.531675464 | None | None | N |
| S/H | 0.2375 | likely_benign | 0.2621 | benign | -1.688 | Destabilizing | 0.932 | D | 0.59 | neutral | None | None | None | None | N |
| S/I | 0.1099 | likely_benign | 0.1178 | benign | -0.007 | Destabilizing | 0.627 | D | 0.61 | neutral | N | 0.501141914 | None | None | N |
| S/K | 0.5431 | ambiguous | 0.6047 | pathogenic | -0.463 | Destabilizing | 0.241 | N | 0.455 | neutral | None | None | None | None | N |
| S/L | 0.0895 | likely_benign | 0.0955 | benign | -0.007 | Destabilizing | 0.241 | N | 0.508 | neutral | None | None | None | None | N |
| S/M | 0.1339 | likely_benign | 0.1447 | benign | 0.019 | Stabilizing | 0.932 | D | 0.588 | neutral | None | None | None | None | N |
| S/N | 0.1484 | likely_benign | 0.1517 | benign | -1.148 | Destabilizing | 0.492 | N | 0.532 | neutral | N | 0.506009016 | None | None | N |
| S/P | 0.9409 | likely_pathogenic | 0.9605 | pathogenic | -0.28 | Destabilizing | 0.932 | D | 0.585 | neutral | None | None | None | None | N |
| S/Q | 0.3755 | ambiguous | 0.4075 | ambiguous | -1.0 | Destabilizing | 0.69 | D | 0.58 | neutral | None | None | None | None | N |
| S/R | 0.4366 | ambiguous | 0.4787 | ambiguous | -0.722 | Destabilizing | 0.001 | N | 0.393 | neutral | N | 0.495445305 | None | None | N |
| S/T | 0.0689 | likely_benign | 0.0708 | benign | -0.839 | Destabilizing | 0.006 | N | 0.213 | neutral | N | 0.418269814 | None | None | N |
| S/V | 0.1146 | likely_benign | 0.1225 | benign | -0.28 | Destabilizing | 0.241 | N | 0.557 | neutral | None | None | None | None | N |
| S/W | 0.249 | likely_benign | 0.2792 | benign | -1.125 | Destabilizing | 0.981 | D | 0.685 | prob.neutral | None | None | None | None | N |
| S/Y | 0.1231 | likely_benign | 0.1353 | benign | -0.699 | Destabilizing | 0.932 | D | 0.621 | 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.