Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25670 | 77233;77234;77235 | chr2:178569124;178569123;178569122 | chr2:179433851;179433850;179433849 |
| N2AB | 24029 | 72310;72311;72312 | chr2:178569124;178569123;178569122 | chr2:179433851;179433850;179433849 |
| N2A | 23102 | 69529;69530;69531 | chr2:178569124;178569123;178569122 | chr2:179433851;179433850;179433849 |
| N2B | 16605 | 50038;50039;50040 | chr2:178569124;178569123;178569122 | chr2:179433851;179433850;179433849 |
| Novex-1 | 16730 | 50413;50414;50415 | chr2:178569124;178569123;178569122 | chr2:179433851;179433850;179433849 |
| Novex-2 | 16797 | 50614;50615;50616 | chr2:178569124;178569123;178569122 | chr2:179433851;179433850;179433849 |
| 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/G | None | None | 0.732 | N | 0.342 | 0.218 | 0.210429274316 | gnomAD-4.0.0 | 2.73734E-06 | None | None | None | None | N | None | 2.99043E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69883E-06 | 0 | 0 |
| S/T | rs774024917  |
-0.104 | 0.147 | N | 0.371 | 0.085 | 0.149567049428 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/T | rs774024917 |
-0.104 | 0.147 | N | 0.371 | 0.085 | 0.149567049428 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 4.83E-05 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/T | rs774024917 |
-0.104 | 0.147 | N | 0.371 | 0.085 | 0.149567049428 | gnomAD-4.0.0 | 5.07503E-06 | None | None | None | None | N | None | 3.49504E-05 | 6.15839E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 6.80504E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0829 | likely_benign | 0.0883 | benign | -0.777 | Destabilizing | 0.059 | N | 0.277 | neutral | None | None | None | None | N |
| S/C | 0.066 | likely_benign | 0.0768 | benign | -0.396 | Destabilizing | 0.987 | D | 0.461 | neutral | N | 0.480954344 | None | None | N |
| S/D | 0.443 | ambiguous | 0.5146 | ambiguous | -0.477 | Destabilizing | 0.703 | D | 0.345 | neutral | None | None | None | None | N |
| S/E | 0.5805 | likely_pathogenic | 0.6318 | pathogenic | -0.387 | Destabilizing | 0.869 | D | 0.346 | neutral | None | None | None | None | N |
| S/F | 0.144 | likely_benign | 0.1746 | benign | -0.662 | Destabilizing | 0.898 | D | 0.408 | neutral | None | None | None | None | N |
| S/G | 0.0963 | likely_benign | 0.1103 | benign | -1.117 | Destabilizing | 0.732 | D | 0.342 | neutral | N | 0.521020462 | None | None | N |
| S/H | 0.2499 | likely_benign | 0.3141 | benign | -1.464 | Destabilizing | 0.984 | D | 0.467 | neutral | None | None | None | None | N |
| S/I | 0.0929 | likely_benign | 0.1145 | benign | 0.05 | Stabilizing | 0.07 | N | 0.29 | neutral | N | 0.480963351 | None | None | N |
| S/K | 0.6833 | likely_pathogenic | 0.7641 | pathogenic | -0.463 | Destabilizing | 0.946 | D | 0.351 | neutral | None | None | None | None | N |
| S/L | 0.0799 | likely_benign | 0.0886 | benign | 0.05 | Stabilizing | 0.614 | D | 0.386 | neutral | None | None | None | None | N |
| S/M | 0.1505 | likely_benign | 0.1708 | benign | 0.167 | Stabilizing | 0.992 | D | 0.476 | neutral | None | None | None | None | N |
| S/N | 0.0877 | likely_benign | 0.1084 | benign | -0.693 | Destabilizing | 0.002 | N | 0.137 | neutral | N | 0.485251663 | None | None | N |
| S/P | 0.2285 | likely_benign | 0.2542 | benign | -0.19 | Destabilizing | 0.99 | D | 0.473 | neutral | None | None | None | None | N |
| S/Q | 0.422 | ambiguous | 0.492 | ambiguous | -0.657 | Destabilizing | 0.973 | D | 0.455 | neutral | None | None | None | None | N |
| S/R | 0.6038 | likely_pathogenic | 0.6917 | pathogenic | -0.575 | Destabilizing | 0.964 | D | 0.459 | neutral | N | 0.475613459 | None | None | N |
| S/T | 0.0709 | likely_benign | 0.0798 | benign | -0.6 | Destabilizing | 0.147 | N | 0.371 | neutral | N | 0.446810705 | None | None | N |
| S/V | 0.1136 | likely_benign | 0.1349 | benign | -0.19 | Destabilizing | 0.373 | N | 0.391 | neutral | None | None | None | None | N |
| S/W | 0.324 | likely_benign | 0.3715 | ambiguous | -0.74 | Destabilizing | 0.998 | D | 0.505 | neutral | None | None | None | None | N |
| S/Y | 0.1287 | likely_benign | 0.1578 | benign | -0.408 | Destabilizing | 0.052 | N | 0.319 | 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.