Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24245 | 72958;72959;72960 | chr2:178573399;178573398;178573397 | chr2:179438126;179438125;179438124 |
| N2AB | 22604 | 68035;68036;68037 | chr2:178573399;178573398;178573397 | chr2:179438126;179438125;179438124 |
| N2A | 21677 | 65254;65255;65256 | chr2:178573399;178573398;178573397 | chr2:179438126;179438125;179438124 |
| N2B | 15180 | 45763;45764;45765 | chr2:178573399;178573398;178573397 | chr2:179438126;179438125;179438124 |
| Novex-1 | 15305 | 46138;46139;46140 | chr2:178573399;178573398;178573397 | chr2:179438126;179438125;179438124 |
| Novex-2 | 15372 | 46339;46340;46341 | chr2:178573399;178573398;178573397 | chr2:179438126;179438125;179438124 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/Y | rs375467956  |
1.025 | 0.662 | N | 0.565 | 0.237 | None | gnomAD-2.1.1 | 1.7E-05 | None | None | None | None | N | None | 1.37836E-04 | 4.78E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| H/Y | rs375467956 |
1.025 | 0.662 | N | 0.565 | 0.237 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| H/Y | rs375467956 |
1.025 | 0.662 | N | 0.565 | 0.237 | None | gnomAD-4.0.0 | 4.36722E-06 | None | None | None | None | N | None | 3.57436E-05 | 2.28613E-05 | None | 0 | 0 | None | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/A | 0.268 | likely_benign | 0.2484 | benign | -0.985 | Destabilizing | 0.345 | N | 0.41 | neutral | None | None | None | None | N |
| H/C | 0.1564 | likely_benign | 0.1493 | benign | -0.35 | Destabilizing | 0.991 | D | 0.548 | neutral | None | None | None | None | N |
| H/D | 0.3651 | ambiguous | 0.3307 | benign | -1.575 | Destabilizing | 0.662 | D | 0.589 | neutral | N | 0.416085153 | None | None | N |
| H/E | 0.3457 | ambiguous | 0.3267 | benign | -1.449 | Destabilizing | 0.345 | N | 0.501 | neutral | None | None | None | None | N |
| H/F | 0.2818 | likely_benign | 0.2438 | benign | 0.468 | Stabilizing | 0.818 | D | 0.658 | neutral | None | None | None | None | N |
| H/G | 0.3873 | ambiguous | 0.3511 | ambiguous | -1.344 | Destabilizing | 0.722 | D | 0.515 | neutral | None | None | None | None | N |
| H/I | 0.3015 | likely_benign | 0.2738 | benign | 0.036 | Stabilizing | 0.39 | N | 0.583 | neutral | None | None | None | None | N |
| H/K | 0.2046 | likely_benign | 0.2103 | benign | -0.697 | Destabilizing | 0.209 | N | 0.419 | neutral | None | None | None | None | N |
| H/L | 0.1155 | likely_benign | 0.1119 | benign | 0.036 | Stabilizing | 0.001 | N | 0.431 | neutral | N | 0.421760331 | None | None | N |
| H/M | 0.4456 | ambiguous | 0.4236 | ambiguous | -0.29 | Destabilizing | 0.818 | D | 0.574 | neutral | None | None | None | None | N |
| H/N | 0.1539 | likely_benign | 0.1349 | benign | -1.214 | Destabilizing | 0.491 | N | 0.522 | neutral | N | 0.459105211 | None | None | N |
| H/P | 0.1245 | likely_benign | 0.118 | benign | -0.289 | Destabilizing | 0.954 | D | 0.635 | neutral | N | 0.296001459 | None | None | N |
| H/Q | 0.1642 | likely_benign | 0.1667 | benign | -0.991 | Destabilizing | 0.491 | N | 0.573 | neutral | N | 0.403886647 | None | None | N |
| H/R | 0.0848 | likely_benign | 0.0904 | benign | -1.162 | Destabilizing | None | N | 0.198 | neutral | N | 0.31690238 | None | None | N |
| H/S | 0.2683 | likely_benign | 0.24 | benign | -1.069 | Destabilizing | 0.561 | D | 0.519 | neutral | None | None | None | None | N |
| H/T | 0.3099 | likely_benign | 0.2799 | benign | -0.824 | Destabilizing | 0.561 | D | 0.549 | neutral | None | None | None | None | N |
| H/V | 0.2528 | likely_benign | 0.2359 | benign | -0.289 | Destabilizing | 0.39 | N | 0.561 | neutral | None | None | None | None | N |
| H/W | 0.4138 | ambiguous | 0.3829 | ambiguous | 0.852 | Stabilizing | 0.991 | D | 0.562 | neutral | None | None | None | None | N |
| H/Y | 0.1037 | likely_benign | 0.0928 | benign | 0.739 | Stabilizing | 0.662 | D | 0.565 | neutral | N | 0.497066167 | 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.