Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27292 | 82099;82100;82101 | chr2:178564258;178564257;178564256 | chr2:179428985;179428984;179428983 |
| N2AB | 25651 | 77176;77177;77178 | chr2:178564258;178564257;178564256 | chr2:179428985;179428984;179428983 |
| N2A | 24724 | 74395;74396;74397 | chr2:178564258;178564257;178564256 | chr2:179428985;179428984;179428983 |
| N2B | 18227 | 54904;54905;54906 | chr2:178564258;178564257;178564256 | chr2:179428985;179428984;179428983 |
| Novex-1 | 18352 | 55279;55280;55281 | chr2:178564258;178564257;178564256 | chr2:179428985;179428984;179428983 |
| Novex-2 | 18419 | 55480;55481;55482 | chr2:178564258;178564257;178564256 | chr2:179428985;179428984;179428983 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | None | None | 0.835 | N | 0.459 | 0.205 | 0.240491677333 | gnomAD-4.0.0 | 6.84442E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99463E-07 | 0 | 0 |
| T/I | rs1060500393  |
0.06 | 0.994 | N | 0.539 | 0.442 | 0.388970301349 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| T/I | rs1060500393 |
0.06 | 0.994 | N | 0.539 | 0.442 | 0.388970301349 | gnomAD-4.0.0 | 1.30049E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.70897E-05 | 0 | 0 |
| T/P | rs1421947280 |
-0.395 | 0.994 | N | 0.537 | 0.322 | 0.310458034454 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| T/P | rs1421947280 |
-0.395 | 0.994 | N | 0.537 | 0.322 | 0.310458034454 | gnomAD-4.0.0 | 3.42221E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.49732E-06 | 0 | 0 |
| T/S | None | None | 0.489 | N | 0.144 | 0.1 | 0.165133752707 | gnomAD-4.0.0 | 2.0534E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 3.46741E-04 | 0 | 0 | 1.65656E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0768 | likely_benign | 0.0837 | benign | -0.929 | Destabilizing | 0.835 | D | 0.459 | neutral | N | 0.453427616 | None | None | I |
| T/C | 0.3813 | ambiguous | 0.4196 | ambiguous | -0.471 | Destabilizing | 1.0 | D | 0.563 | neutral | None | None | None | None | I |
| T/D | 0.3187 | likely_benign | 0.3601 | ambiguous | -0.009 | Destabilizing | 0.942 | D | 0.47 | neutral | None | None | None | None | I |
| T/E | 0.3479 | ambiguous | 0.3966 | ambiguous | 0.039 | Stabilizing | 0.97 | D | 0.453 | neutral | None | None | None | None | I |
| T/F | 0.2951 | likely_benign | 0.3315 | benign | -0.949 | Destabilizing | 0.999 | D | 0.643 | neutral | None | None | None | None | I |
| T/G | 0.2212 | likely_benign | 0.244 | benign | -1.224 | Destabilizing | 0.97 | D | 0.455 | neutral | None | None | None | None | I |
| T/H | 0.2782 | likely_benign | 0.3129 | benign | -1.339 | Destabilizing | 0.999 | D | 0.639 | neutral | None | None | None | None | I |
| T/I | 0.1589 | likely_benign | 0.1811 | benign | -0.221 | Destabilizing | 0.994 | D | 0.539 | neutral | N | 0.480116699 | None | None | I |
| T/K | 0.2483 | likely_benign | 0.2958 | benign | -0.548 | Destabilizing | 0.97 | D | 0.447 | neutral | None | None | None | None | I |
| T/L | 0.1084 | likely_benign | 0.125 | benign | -0.221 | Destabilizing | 0.985 | D | 0.466 | neutral | None | None | None | None | I |
| T/M | 0.0878 | likely_benign | 0.0921 | benign | -0.054 | Destabilizing | 1.0 | D | 0.549 | neutral | None | None | None | None | I |
| T/N | 0.0889 | likely_benign | 0.0959 | benign | -0.648 | Destabilizing | 0.248 | N | 0.239 | neutral | N | 0.493630712 | None | None | I |
| T/P | 0.0997 | likely_benign | 0.1179 | benign | -0.425 | Destabilizing | 0.994 | D | 0.537 | neutral | N | 0.499287247 | None | None | I |
| T/Q | 0.2736 | likely_benign | 0.3117 | benign | -0.673 | Destabilizing | 0.996 | D | 0.551 | neutral | None | None | None | None | I |
| T/R | 0.2222 | likely_benign | 0.2671 | benign | -0.401 | Destabilizing | 0.996 | D | 0.536 | neutral | None | None | None | None | I |
| T/S | 0.0962 | likely_benign | 0.1021 | benign | -0.988 | Destabilizing | 0.489 | N | 0.144 | neutral | N | 0.46082486 | None | None | I |
| T/V | 0.1232 | likely_benign | 0.1431 | benign | -0.425 | Destabilizing | 0.985 | D | 0.426 | neutral | None | None | None | None | I |
| T/W | 0.6973 | likely_pathogenic | 0.7345 | pathogenic | -0.916 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | I |
| T/Y | 0.295 | likely_benign | 0.3415 | ambiguous | -0.656 | Destabilizing | 0.999 | D | 0.638 | 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.