Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19567 | 58924;58925;58926 | chr2:178593601;178593600;178593599 | chr2:179458328;179458327;179458326 |
| N2AB | 17926 | 54001;54002;54003 | chr2:178593601;178593600;178593599 | chr2:179458328;179458327;179458326 |
| N2A | 16999 | 51220;51221;51222 | chr2:178593601;178593600;178593599 | chr2:179458328;179458327;179458326 |
| N2B | 10502 | 31729;31730;31731 | chr2:178593601;178593600;178593599 | chr2:179458328;179458327;179458326 |
| Novex-1 | 10627 | 32104;32105;32106 | chr2:178593601;178593600;178593599 | chr2:179458328;179458327;179458326 |
| Novex-2 | 10694 | 32305;32306;32307 | chr2:178593601;178593600;178593599 | chr2:179458328;179458327;179458326 |
| 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/A | rs763514219  |
-1.274 | 0.435 | N | 0.429 | 0.186 | 0.389283895039 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.96E-06 | 0 |
| V/A | rs763514219 |
-1.274 | 0.435 | N | 0.429 | 0.186 | 0.389283895039 | gnomAD-4.0.0 | 1.02704E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 3.47464E-04 | 1.16962E-05 | 0 | 0 |
| V/L | None | None | 0.002 | N | 0.191 | 0.188 | 0.290962096972 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| V/M | rs1448926202 |
-0.453 | 0.868 | N | 0.483 | 0.152 | 0.415313616471 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 1.14837E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/M | rs1448926202 |
-0.453 | 0.868 | N | 0.483 | 0.152 | 0.415313616471 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/M | rs1448926202 |
-0.453 | 0.868 | N | 0.483 | 0.152 | 0.415313616471 | gnomAD-4.0.0 | 1.31544E-05 | None | None | None | None | N | None | 4.82928E-05 | 0 | 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 | 0.2181 | likely_benign | 0.1952 | benign | -0.882 | Destabilizing | 0.435 | N | 0.429 | neutral | N | 0.462191163 | None | None | N |
| V/C | 0.7092 | likely_pathogenic | 0.6651 | pathogenic | -0.83 | Destabilizing | 0.995 | D | 0.529 | neutral | None | None | None | None | N |
| V/D | 0.2643 | likely_benign | 0.2602 | benign | -0.364 | Destabilizing | 0.553 | D | 0.641 | neutral | None | None | None | None | N |
| V/E | 0.1802 | likely_benign | 0.169 | benign | -0.379 | Destabilizing | 0.002 | N | 0.491 | neutral | N | 0.370241007 | None | None | N |
| V/F | 0.1551 | likely_benign | 0.1326 | benign | -0.625 | Destabilizing | 0.897 | D | 0.561 | neutral | None | None | None | None | N |
| V/G | 0.3201 | likely_benign | 0.3039 | benign | -1.151 | Destabilizing | 0.651 | D | 0.648 | neutral | N | 0.494476939 | None | None | N |
| V/H | 0.5086 | ambiguous | 0.45 | ambiguous | -0.574 | Destabilizing | 0.985 | D | 0.675 | prob.neutral | None | None | None | None | N |
| V/I | 0.076 | likely_benign | 0.0666 | benign | -0.271 | Destabilizing | 0.008 | N | 0.195 | neutral | None | None | None | None | N |
| V/K | 0.3348 | likely_benign | 0.2898 | benign | -0.776 | Destabilizing | 0.553 | D | 0.639 | neutral | None | None | None | None | N |
| V/L | 0.1339 | likely_benign | 0.1082 | benign | -0.271 | Destabilizing | 0.002 | N | 0.191 | neutral | N | 0.448107145 | None | None | N |
| V/M | 0.1593 | likely_benign | 0.1254 | benign | -0.416 | Destabilizing | 0.868 | D | 0.483 | neutral | N | 0.50559801 | None | None | N |
| V/N | 0.2725 | likely_benign | 0.226 | benign | -0.647 | Destabilizing | 0.897 | D | 0.676 | prob.neutral | None | None | None | None | N |
| V/P | 0.4419 | ambiguous | 0.4093 | ambiguous | -0.438 | Destabilizing | 0.946 | D | 0.678 | prob.neutral | None | None | None | None | N |
| V/Q | 0.2803 | likely_benign | 0.2494 | benign | -0.752 | Destabilizing | 0.182 | N | 0.505 | neutral | None | None | None | None | N |
| V/R | 0.3259 | likely_benign | 0.2972 | benign | -0.342 | Destabilizing | 0.897 | D | 0.677 | prob.neutral | None | None | None | None | N |
| V/S | 0.244 | likely_benign | 0.2167 | benign | -1.162 | Destabilizing | 0.712 | D | 0.625 | neutral | None | None | None | None | N |
| V/T | 0.2036 | likely_benign | 0.1695 | benign | -1.053 | Destabilizing | 0.712 | D | 0.439 | neutral | None | None | None | None | N |
| V/W | 0.753 | likely_pathogenic | 0.709 | pathogenic | -0.779 | Destabilizing | 0.995 | D | 0.712 | prob.delet. | None | None | None | None | N |
| V/Y | 0.4451 | ambiguous | 0.3934 | ambiguous | -0.47 | Destabilizing | 0.982 | D | 0.552 | 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.