Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23371 | 70336;70337;70338 | chr2:178576021;178576020;178576019 | chr2:179440748;179440747;179440746 |
| N2AB | 21730 | 65413;65414;65415 | chr2:178576021;178576020;178576019 | chr2:179440748;179440747;179440746 |
| N2A | 20803 | 62632;62633;62634 | chr2:178576021;178576020;178576019 | chr2:179440748;179440747;179440746 |
| N2B | 14306 | 43141;43142;43143 | chr2:178576021;178576020;178576019 | chr2:179440748;179440747;179440746 |
| Novex-1 | 14431 | 43516;43517;43518 | chr2:178576021;178576020;178576019 | chr2:179440748;179440747;179440746 |
| Novex-2 | 14498 | 43717;43718;43719 | chr2:178576021;178576020;178576019 | chr2:179440748;179440747;179440746 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs56141309  |
0.07 | 1.0 | N | 0.63 | 0.47 | 0.743538347216 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | I | None | 0 | 5.8E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/C | rs56141309 |
0.07 | 1.0 | N | 0.63 | 0.47 | 0.743538347216 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/C | rs56141309 |
0.07 | 1.0 | N | 0.63 | 0.47 | 0.743538347216 | gnomAD-4.0.0 | 6.41267E-06 | None | None | None | None | I | None | 0 | 3.39075E-05 | None | 0 | 0 | None | 0 | 0 | 7.18845E-06 | 0 | 0 |
| R/H | rs767208489 |
-0.661 | 1.0 | N | 0.549 | 0.426 | 0.373537453441 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | I | None | 0 | 2.9E-05 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| R/H | rs767208489 |
-0.661 | 1.0 | N | 0.549 | 0.426 | 0.373537453441 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 0 | 1.31096E-04 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/H | rs767208489 |
-0.661 | 1.0 | N | 0.549 | 0.426 | 0.373537453441 | gnomAD-4.0.0 | 9.92059E-06 | None | None | None | None | I | None | 2.6713E-05 | 6.66956E-05 | None | 3.37998E-05 | 2.23075E-05 | None | 0 | 0 | 5.08821E-06 | 2.19664E-05 | 0 |
| R/P | rs767208489 |
None | 0.998 | N | 0.603 | 0.542 | 0.672494282746 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/P | rs767208489 |
None | 0.998 | N | 0.603 | 0.542 | 0.672494282746 | gnomAD-4.0.0 | 4.96029E-06 | None | None | None | None | I | None | 2.6713E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 5.08821E-06 | 0 | 0 |
| R/S | None | None | 0.993 | N | 0.578 | 0.405 | 0.489869231792 | gnomAD-4.0.0 | 3.18647E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.72502E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9258 | likely_pathogenic | 0.9644 | pathogenic | -0.016 | Destabilizing | 0.845 | D | 0.594 | neutral | None | None | None | None | I |
| R/C | 0.3681 | ambiguous | 0.5017 | ambiguous | -0.325 | Destabilizing | 1.0 | D | 0.63 | neutral | N | 0.486542157 | None | None | I |
| R/D | 0.9847 | likely_pathogenic | 0.993 | pathogenic | -0.401 | Destabilizing | 0.996 | D | 0.603 | neutral | None | None | None | None | I |
| R/E | 0.8791 | likely_pathogenic | 0.937 | pathogenic | -0.373 | Destabilizing | 0.957 | D | 0.571 | neutral | None | None | None | None | I |
| R/F | 0.8031 | likely_pathogenic | 0.8889 | pathogenic | -0.374 | Destabilizing | 0.975 | D | 0.616 | neutral | None | None | None | None | I |
| R/G | 0.9001 | likely_pathogenic | 0.9555 | pathogenic | -0.125 | Destabilizing | 0.977 | D | 0.572 | neutral | N | 0.497644973 | None | None | I |
| R/H | 0.2036 | likely_benign | 0.3004 | benign | -0.619 | Destabilizing | 1.0 | D | 0.549 | neutral | N | 0.505083509 | None | None | I |
| R/I | 0.5499 | ambiguous | 0.6993 | pathogenic | 0.222 | Stabilizing | 0.845 | D | 0.583 | neutral | None | None | None | None | I |
| R/K | 0.1915 | likely_benign | 0.2727 | benign | -0.274 | Destabilizing | 0.901 | D | 0.511 | neutral | None | None | None | None | I |
| R/L | 0.6359 | likely_pathogenic | 0.7639 | pathogenic | 0.222 | Stabilizing | 0.913 | D | 0.592 | neutral | D | 0.53113396 | None | None | I |
| R/M | 0.6871 | likely_pathogenic | 0.8219 | pathogenic | -0.175 | Destabilizing | 0.987 | D | 0.568 | neutral | None | None | None | None | I |
| R/N | 0.9322 | likely_pathogenic | 0.9687 | pathogenic | -0.206 | Destabilizing | 0.996 | D | 0.559 | neutral | None | None | None | None | I |
| R/P | 0.9945 | likely_pathogenic | 0.9967 | pathogenic | 0.159 | Stabilizing | 0.998 | D | 0.603 | neutral | N | 0.509254768 | None | None | I |
| R/Q | 0.2447 | likely_benign | 0.3686 | ambiguous | -0.223 | Destabilizing | 0.996 | D | 0.571 | neutral | None | None | None | None | I |
| R/S | 0.9257 | likely_pathogenic | 0.9681 | pathogenic | -0.328 | Destabilizing | 0.993 | D | 0.578 | neutral | N | 0.501907131 | None | None | I |
| R/T | 0.811 | likely_pathogenic | 0.913 | pathogenic | -0.212 | Destabilizing | 0.916 | D | 0.602 | neutral | None | None | None | None | I |
| R/V | 0.72 | likely_pathogenic | 0.8285 | pathogenic | 0.159 | Stabilizing | 0.033 | N | 0.572 | neutral | None | None | None | None | I |
| R/W | 0.3739 | ambiguous | 0.4937 | ambiguous | -0.598 | Destabilizing | 0.999 | D | 0.667 | neutral | None | None | None | None | I |
| R/Y | 0.6028 | likely_pathogenic | 0.7447 | pathogenic | -0.21 | Destabilizing | 0.987 | D | 0.61 | 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.