Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31959 | 96100;96101;96102 | chr2:178544354;178544353;178544352 | chr2:179409081;179409080;179409079 |
| N2AB | 30318 | 91177;91178;91179 | chr2:178544354;178544353;178544352 | chr2:179409081;179409080;179409079 |
| N2A | 29391 | 88396;88397;88398 | chr2:178544354;178544353;178544352 | chr2:179409081;179409080;179409079 |
| N2B | 22894 | 68905;68906;68907 | chr2:178544354;178544353;178544352 | chr2:179409081;179409080;179409079 |
| Novex-1 | 23019 | 69280;69281;69282 | chr2:178544354;178544353;178544352 | chr2:179409081;179409080;179409079 |
| Novex-2 | 23086 | 69481;69482;69483 | chr2:178544354;178544353;178544352 | chr2:179409081;179409080;179409079 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/E | rs761732372  |
-2.451 | 0.801 | N | 0.491 | 0.394 | None | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | N | None | 1.29149E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/E | rs761732372 |
-2.451 | 0.801 | N | 0.491 | 0.394 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/E | rs761732372 |
-2.451 | 0.801 | N | 0.491 | 0.394 | None | gnomAD-4.0.0 | 8.96879E-06 | None | None | None | None | N | None | 1.01513E-04 | 1.6952E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/L | rs1372238245 |
-0.241 | 0.625 | N | 0.405 | 0.136 | 0.423360453849 | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | N | None | 0 | 5.8E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/L | rs1372238245 |
-0.241 | 0.625 | N | 0.405 | 0.136 | 0.423360453849 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 1.30976E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/L | rs1372238245 |
-0.241 | 0.625 | N | 0.405 | 0.136 | 0.423360453849 | gnomAD-4.0.0 | 6.40594E-06 | None | None | None | None | N | None | 0 | 8.474E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2053 | likely_benign | 0.2106 | benign | -1.872 | Destabilizing | 0.005 | N | 0.225 | neutral | N | 0.460894723 | None | None | N |
| V/C | 0.6519 | likely_pathogenic | 0.6572 | pathogenic | -1.211 | Destabilizing | 0.993 | D | 0.525 | neutral | None | None | None | None | N |
| V/D | 0.8495 | likely_pathogenic | 0.8592 | pathogenic | -2.51 | Highly Destabilizing | 0.915 | D | 0.526 | neutral | None | None | None | None | N |
| V/E | 0.7549 | likely_pathogenic | 0.7616 | pathogenic | -2.357 | Highly Destabilizing | 0.801 | D | 0.491 | neutral | N | 0.48466042 | None | None | N |
| V/F | 0.4345 | ambiguous | 0.4617 | ambiguous | -1.286 | Destabilizing | 0.974 | D | 0.539 | neutral | None | None | None | None | N |
| V/G | 0.3538 | ambiguous | 0.3797 | ambiguous | -2.298 | Highly Destabilizing | 0.454 | N | 0.485 | neutral | N | 0.479206371 | None | None | N |
| V/H | 0.8828 | likely_pathogenic | 0.8894 | pathogenic | -1.874 | Destabilizing | 0.998 | D | 0.573 | neutral | None | None | None | None | N |
| V/I | 0.0893 | likely_benign | 0.0954 | benign | -0.716 | Destabilizing | 0.688 | D | 0.478 | neutral | None | None | None | None | N |
| V/K | 0.7543 | likely_pathogenic | 0.7599 | pathogenic | -1.68 | Destabilizing | 0.842 | D | 0.481 | neutral | None | None | None | None | N |
| V/L | 0.3396 | likely_benign | 0.3712 | ambiguous | -0.716 | Destabilizing | 0.625 | D | 0.405 | neutral | N | 0.490198909 | None | None | N |
| V/M | 0.3106 | likely_benign | 0.3442 | ambiguous | -0.584 | Destabilizing | 0.989 | D | 0.561 | neutral | N | 0.482359923 | None | None | N |
| V/N | 0.6827 | likely_pathogenic | 0.7263 | pathogenic | -1.841 | Destabilizing | 0.974 | D | 0.58 | neutral | None | None | None | None | N |
| V/P | 0.4856 | ambiguous | 0.4621 | ambiguous | -1.074 | Destabilizing | 0.002 | N | 0.401 | neutral | None | None | None | None | N |
| V/Q | 0.7247 | likely_pathogenic | 0.733 | pathogenic | -1.828 | Destabilizing | 0.974 | D | 0.563 | neutral | None | None | None | None | N |
| V/R | 0.7257 | likely_pathogenic | 0.7273 | pathogenic | -1.337 | Destabilizing | 0.974 | D | 0.581 | neutral | None | None | None | None | N |
| V/S | 0.4238 | ambiguous | 0.4514 | ambiguous | -2.317 | Highly Destabilizing | 0.525 | D | 0.473 | neutral | None | None | None | None | N |
| V/T | 0.3271 | likely_benign | 0.3507 | ambiguous | -2.039 | Highly Destabilizing | 0.688 | D | 0.457 | neutral | None | None | None | None | N |
| V/W | 0.9485 | likely_pathogenic | 0.9503 | pathogenic | -1.683 | Destabilizing | 0.998 | D | 0.616 | neutral | None | None | None | None | N |
| V/Y | 0.8175 | likely_pathogenic | 0.8263 | pathogenic | -1.299 | Destabilizing | 0.991 | D | 0.538 | 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.