Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30448 | 91567;91568;91569 | chr2:178551189;178551188;178551187 | chr2:179415916;179415915;179415914 |
| N2AB | 28807 | 86644;86645;86646 | chr2:178551189;178551188;178551187 | chr2:179415916;179415915;179415914 |
| N2A | 27880 | 83863;83864;83865 | chr2:178551189;178551188;178551187 | chr2:179415916;179415915;179415914 |
| N2B | 21383 | 64372;64373;64374 | chr2:178551189;178551188;178551187 | chr2:179415916;179415915;179415914 |
| Novex-1 | 21508 | 64747;64748;64749 | chr2:178551189;178551188;178551187 | chr2:179415916;179415915;179415914 |
| Novex-2 | 21575 | 64948;64949;64950 | chr2:178551189;178551188;178551187 | chr2:179415916;179415915;179415914 |
| 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 | rs756030714  |
-0.26 | 0.992 | N | 0.708 | 0.308 | None | gnomAD-2.1.1 | 3.93E-05 | None | None | None | None | I | None | 4.13E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 7.82E-05 | 0 |
| R/C | rs756030714 |
-0.26 | 0.992 | N | 0.708 | 0.308 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | I | None | 7.25E-05 | 0 | 0 | 0 | 0 | None | 9.44E-05 | 0 | 1.47E-05 | 0 | 0 |
| R/C | rs756030714 |
-0.26 | 0.992 | N | 0.708 | 0.308 | None | gnomAD-4.0.0 | 2.9752E-05 | None | None | None | None | I | None | 6.68163E-05 | 0 | None | 0 | 0 | None | 3.12774E-05 | 0 | 3.30607E-05 | 1.09791E-05 | 1.60133E-05 |
| R/H | rs374474227 |
-1.102 | 0.011 | N | 0.271 | 0.119 | None | gnomAD-2.1.1 | 7.14E-05 | None | None | None | None | I | None | 0 | 2.83E-05 | None | 0 | 0 | None | 2.94195E-04 | None | 0 | 7.82E-05 | 0 |
| R/H | rs374474227 |
-1.102 | 0.011 | N | 0.271 | 0.119 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 2.07211E-04 | 0 |
| R/H | rs374474227 |
-1.102 | 0.011 | N | 0.271 | 0.119 | None | gnomAD-4.0.0 | 6.8799E-05 | None | None | None | None | I | None | 1.33593E-05 | 3.33511E-05 | None | 3.37952E-05 | 0 | None | 0 | 1.64582E-04 | 6.44252E-05 | 2.85476E-04 | 6.40492E-05 |
| R/L | None | None | 0.417 | N | 0.577 | 0.174 | 0.396794106654 | gnomAD-4.0.0 | 6.84316E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.9957E-07 | 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 | 0.8016 | likely_pathogenic | 0.7222 | pathogenic | -0.148 | Destabilizing | 0.272 | N | 0.585 | neutral | None | None | None | None | I |
| R/C | 0.3984 | ambiguous | 0.2835 | benign | -0.061 | Destabilizing | 0.992 | D | 0.708 | prob.delet. | N | 0.482248643 | None | None | I |
| R/D | 0.9283 | likely_pathogenic | 0.8845 | pathogenic | 0.082 | Stabilizing | 0.567 | D | 0.545 | neutral | None | None | None | None | I |
| R/E | 0.7676 | likely_pathogenic | 0.6798 | pathogenic | 0.185 | Stabilizing | 0.157 | N | 0.543 | neutral | None | None | None | None | I |
| R/F | 0.8156 | likely_pathogenic | 0.7225 | pathogenic | -0.121 | Destabilizing | 0.567 | D | 0.667 | neutral | None | None | None | None | I |
| R/G | 0.6256 | likely_pathogenic | 0.5274 | ambiguous | -0.427 | Destabilizing | 0.417 | N | 0.603 | neutral | N | 0.458833065 | None | None | I |
| R/H | 0.1782 | likely_benign | 0.1238 | benign | -0.97 | Destabilizing | 0.011 | N | 0.271 | neutral | N | 0.38791433 | None | None | I |
| R/I | 0.7389 | likely_pathogenic | 0.6511 | pathogenic | 0.577 | Stabilizing | 0.726 | D | 0.666 | neutral | None | None | None | None | I |
| R/K | 0.2065 | likely_benign | 0.1756 | benign | -0.145 | Destabilizing | 0.005 | N | 0.173 | neutral | None | None | None | None | I |
| R/L | 0.5814 | likely_pathogenic | 0.473 | ambiguous | 0.577 | Stabilizing | 0.417 | N | 0.577 | neutral | N | 0.457792915 | None | None | I |
| R/M | 0.6643 | likely_pathogenic | 0.5632 | ambiguous | 0.149 | Stabilizing | 0.968 | D | 0.576 | neutral | None | None | None | None | I |
| R/N | 0.8364 | likely_pathogenic | 0.7421 | pathogenic | 0.287 | Stabilizing | 0.157 | N | 0.535 | neutral | None | None | None | None | I |
| R/P | 0.9624 | likely_pathogenic | 0.9543 | pathogenic | 0.358 | Stabilizing | 0.836 | D | 0.651 | neutral | N | 0.452099094 | None | None | I |
| R/Q | 0.2199 | likely_benign | 0.1679 | benign | 0.169 | Stabilizing | 0.567 | D | 0.548 | neutral | None | None | None | None | I |
| R/S | 0.8339 | likely_pathogenic | 0.7489 | pathogenic | -0.22 | Destabilizing | 0.417 | N | 0.604 | neutral | N | 0.371790084 | None | None | I |
| R/T | 0.7087 | likely_pathogenic | 0.5994 | pathogenic | 0.05 | Stabilizing | 0.431 | N | 0.556 | neutral | None | None | None | None | I |
| R/V | 0.7855 | likely_pathogenic | 0.7095 | pathogenic | 0.358 | Stabilizing | 0.726 | D | 0.644 | neutral | None | None | None | None | I |
| R/W | 0.3527 | ambiguous | 0.2804 | benign | 0.004 | Stabilizing | 0.968 | D | 0.736 | prob.delet. | None | None | None | None | I |
| R/Y | 0.5978 | likely_pathogenic | 0.4743 | ambiguous | 0.366 | Stabilizing | 0.396 | N | 0.647 | 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.