Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23498 | 70717;70718;70719 | chr2:178575640;178575639;178575638 | chr2:179440367;179440366;179440365 |
| N2AB | 21857 | 65794;65795;65796 | chr2:178575640;178575639;178575638 | chr2:179440367;179440366;179440365 |
| N2A | 20930 | 63013;63014;63015 | chr2:178575640;178575639;178575638 | chr2:179440367;179440366;179440365 |
| N2B | 14433 | 43522;43523;43524 | chr2:178575640;178575639;178575638 | chr2:179440367;179440366;179440365 |
| Novex-1 | 14558 | 43897;43898;43899 | chr2:178575640;178575639;178575638 | chr2:179440367;179440366;179440365 |
| Novex-2 | 14625 | 44098;44099;44100 | chr2:178575640;178575639;178575638 | chr2:179440367;179440366;179440365 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/D | rs770261949  |
0.126 | None | N | 0.233 | 0.076 | 0.159798565429 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.58E-05 | None | 0 | None | 0 | 0 | 0 |
| G/S | rs370771532 |
-0.149 | 0.442 | N | 0.399 | 0.154 | None | gnomAD-2.1.1 | 2.32246E-04 | None | None | None | None | N | None | 4.54658E-04 | 0 | None | 4.06425E-03 | 0 | None | 3.27E-05 | None | 0 | 7.82E-05 | 1.40568E-04 |
| G/S | rs370771532 |
-0.149 | 0.442 | N | 0.399 | 0.154 | None | gnomAD-3.1.2 | 2.43328E-04 | None | None | None | None | N | None | 3.86138E-04 | 0 | 0 | 3.4642E-03 | 0 | None | 0 | 0 | 1.32372E-04 | 0 | 0 |
| G/S | rs370771532 |
-0.149 | 0.442 | N | 0.399 | 0.154 | None | gnomAD-4.0.0 | 1.80983E-04 | None | None | None | None | N | None | 2.93733E-04 | 0 | None | 3.27858E-03 | 0 | None | 0 | 0 | 1.30548E-04 | 2.19631E-05 | 2.72253E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/A | 0.1362 | likely_benign | 0.152 | benign | -0.221 | Destabilizing | 0.22 | N | 0.399 | neutral | N | 0.49966771 | None | None | N |
| G/C | 0.2189 | likely_benign | 0.2413 | benign | -0.851 | Destabilizing | 0.983 | D | 0.661 | neutral | D | 0.530395718 | None | None | N |
| G/D | 0.1342 | likely_benign | 0.1471 | benign | -0.172 | Destabilizing | None | N | 0.233 | neutral | N | 0.449330935 | None | None | N |
| G/E | 0.201 | likely_benign | 0.2308 | benign | -0.322 | Destabilizing | 0.157 | N | 0.437 | neutral | None | None | None | None | N |
| G/F | 0.5457 | ambiguous | 0.6265 | pathogenic | -0.922 | Destabilizing | 0.89 | D | 0.611 | neutral | None | None | None | None | N |
| G/H | 0.3185 | likely_benign | 0.3261 | benign | -0.469 | Destabilizing | 0.909 | D | 0.527 | neutral | None | None | None | None | N |
| G/I | 0.372 | ambiguous | 0.4741 | ambiguous | -0.335 | Destabilizing | 0.726 | D | 0.602 | neutral | None | None | None | None | N |
| G/K | 0.4514 | ambiguous | 0.4856 | ambiguous | -0.615 | Destabilizing | 0.567 | D | 0.476 | neutral | None | None | None | None | N |
| G/L | 0.4168 | ambiguous | 0.4893 | ambiguous | -0.335 | Destabilizing | 0.567 | D | 0.589 | neutral | None | None | None | None | N |
| G/M | 0.4529 | ambiguous | 0.5136 | ambiguous | -0.443 | Destabilizing | 0.968 | D | 0.626 | neutral | None | None | None | None | N |
| G/N | 0.1463 | likely_benign | 0.1608 | benign | -0.287 | Destabilizing | 0.001 | N | 0.185 | neutral | None | None | None | None | N |
| G/P | 0.7938 | likely_pathogenic | 0.8382 | pathogenic | -0.264 | Destabilizing | 0.726 | D | 0.517 | neutral | None | None | None | None | N |
| G/Q | 0.2964 | likely_benign | 0.3117 | benign | -0.518 | Destabilizing | 0.567 | D | 0.519 | neutral | None | None | None | None | N |
| G/R | 0.363 | ambiguous | 0.3897 | ambiguous | -0.265 | Destabilizing | 0.715 | D | 0.516 | neutral | N | 0.519983099 | None | None | N |
| G/S | 0.0884 | likely_benign | 0.0934 | benign | -0.495 | Destabilizing | 0.442 | N | 0.399 | neutral | N | 0.467787614 | None | None | N |
| G/T | 0.1698 | likely_benign | 0.2015 | benign | -0.561 | Destabilizing | 0.272 | N | 0.467 | neutral | None | None | None | None | N |
| G/V | 0.2678 | likely_benign | 0.3419 | ambiguous | -0.264 | Destabilizing | 0.667 | D | 0.587 | neutral | D | 0.530142229 | None | None | N |
| G/W | 0.4445 | ambiguous | 0.4857 | ambiguous | -1.082 | Destabilizing | 0.968 | D | 0.627 | neutral | None | None | None | None | N |
| G/Y | 0.3881 | ambiguous | 0.4508 | ambiguous | -0.715 | Destabilizing | 0.89 | D | 0.613 | 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.