Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 9067 | 27424;27425;27426 | chr2:178712826;178712825;178712824 | chr2:179577553;179577552;179577551 |
| N2AB | 8750 | 26473;26474;26475 | chr2:178712826;178712825;178712824 | chr2:179577553;179577552;179577551 |
| N2A | 7823 | 23692;23693;23694 | chr2:178712826;178712825;178712824 | chr2:179577553;179577552;179577551 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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/L | rs543334845  |
-0.431 | 0.018 | N | 0.273 | 0.148 | 0.295623431141 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 0 | 0 |
| V/L | rs543334845 |
-0.431 | 0.018 | N | 0.273 | 0.148 | 0.295623431141 | gnomAD-4.0.0 | 3.18277E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.86574E-05 | 0 |
| V/M | rs543334845 |
-0.637 | 0.216 | N | 0.261 | 0.144 | 0.3085936734 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 9.81E-05 | None | 0 | 0 | 0 |
| V/M | rs543334845 |
-0.637 | 0.216 | N | 0.261 | 0.144 | 0.3085936734 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.06954E-04 | 0 |
| V/M | rs543334845 |
-0.637 | 0.216 | N | 0.261 | 0.144 | 0.3085936734 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| V/M | rs543334845 |
-0.637 | 0.216 | N | 0.261 | 0.144 | 0.3085936734 | gnomAD-4.0.0 | 6.40482E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 6.7008E-05 | 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 | 0.2748 | likely_benign | 0.3119 | benign | -1.682 | Destabilizing | 0.183 | N | 0.296 | neutral | D | 0.531966253 | None | None | I |
| V/C | 0.7615 | likely_pathogenic | 0.7798 | pathogenic | -1.021 | Destabilizing | 0.94 | D | 0.519 | neutral | None | None | None | None | I |
| V/D | 0.5393 | ambiguous | 0.6283 | pathogenic | -1.623 | Destabilizing | 0.836 | D | 0.61 | neutral | None | None | None | None | I |
| V/E | 0.4225 | ambiguous | 0.5128 | ambiguous | -1.589 | Destabilizing | 0.523 | D | 0.54 | neutral | N | 0.491842665 | None | None | I |
| V/F | 0.1265 | likely_benign | 0.1373 | benign | -1.258 | Destabilizing | 0.002 | N | 0.286 | neutral | None | None | None | None | I |
| V/G | 0.3409 | ambiguous | 0.4048 | ambiguous | -2.048 | Highly Destabilizing | 0.523 | D | 0.519 | neutral | N | 0.49600824 | None | None | I |
| V/H | 0.637 | likely_pathogenic | 0.6922 | pathogenic | -1.683 | Destabilizing | 0.836 | D | 0.565 | neutral | None | None | None | None | I |
| V/I | 0.0666 | likely_benign | 0.0662 | benign | -0.752 | Destabilizing | 0.001 | N | 0.089 | neutral | None | None | None | None | I |
| V/K | 0.4587 | ambiguous | 0.5502 | ambiguous | -1.355 | Destabilizing | 0.418 | N | 0.537 | neutral | None | None | None | None | I |
| V/L | 0.1552 | likely_benign | 0.1713 | benign | -0.752 | Destabilizing | 0.018 | N | 0.273 | neutral | N | 0.482364152 | None | None | I |
| V/M | 0.1243 | likely_benign | 0.1338 | benign | -0.521 | Destabilizing | 0.216 | N | 0.261 | neutral | N | 0.475419537 | None | None | I |
| V/N | 0.4553 | ambiguous | 0.513 | ambiguous | -1.152 | Destabilizing | 0.836 | D | 0.596 | neutral | None | None | None | None | I |
| V/P | 0.7732 | likely_pathogenic | 0.8058 | pathogenic | -1.028 | Destabilizing | 0.94 | D | 0.579 | neutral | None | None | None | None | I |
| V/Q | 0.4475 | ambiguous | 0.5178 | ambiguous | -1.281 | Destabilizing | 0.836 | D | 0.559 | neutral | None | None | None | None | I |
| V/R | 0.3877 | ambiguous | 0.4719 | ambiguous | -0.897 | Destabilizing | 0.836 | D | 0.599 | neutral | None | None | None | None | I |
| V/S | 0.3487 | ambiguous | 0.3981 | ambiguous | -1.694 | Destabilizing | 0.264 | N | 0.439 | neutral | None | None | None | None | I |
| V/T | 0.2931 | likely_benign | 0.3225 | benign | -1.548 | Destabilizing | 0.01 | N | 0.121 | neutral | None | None | None | None | I |
| V/W | 0.6864 | likely_pathogenic | 0.7339 | pathogenic | -1.525 | Destabilizing | 0.983 | D | 0.547 | neutral | None | None | None | None | I |
| V/Y | 0.4359 | ambiguous | 0.4794 | ambiguous | -1.222 | Destabilizing | 0.01 | N | 0.28 | neutral | None | None | None | None | I |
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.