Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3190 | 9793;9794;9795 | chr2:178766516;178766515;178766514 | chr2:179631243;179631242;179631241 |
| N2AB | 3190 | 9793;9794;9795 | chr2:178766516;178766515;178766514 | chr2:179631243;179631242;179631241 |
| N2A | 3190 | 9793;9794;9795 | chr2:178766516;178766515;178766514 | chr2:179631243;179631242;179631241 |
| N2B | 3144 | 9655;9656;9657 | chr2:178766516;178766515;178766514 | chr2:179631243;179631242;179631241 |
| Novex-1 | 3144 | 9655;9656;9657 | chr2:178766516;178766515;178766514 | chr2:179631243;179631242;179631241 |
| Novex-2 | 3144 | 9655;9656;9657 | chr2:178766516;178766515;178766514 | chr2:179631243;179631242;179631241 |
| Novex-3 | 3190 | 9793;9794;9795 | chr2:178766516;178766515;178766514 | chr2:179631243;179631242;179631241 |
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/F | rs370856494  |
-1.335 | 0.062 | N | 0.416 | 0.079 | None | gnomAD-2.1.1 | 7.97E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.53253E-04 | None | 0 | 0 | 0 |
| V/F | rs370856494 |
-1.335 | 0.062 | N | 0.416 | 0.079 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 1.03605E-03 | 0 |
| V/F | rs370856494 |
-1.335 | 0.062 | N | 0.416 | 0.079 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| V/F | rs370856494 |
-1.335 | 0.062 | N | 0.416 | 0.079 | None | gnomAD-4.0.0 | 3.53145E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.54238E-06 | 5.59947E-04 | 4.79939E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.3055 | likely_benign | 0.2721 | benign | -0.265 | Destabilizing | 0.027 | N | 0.325 | neutral | N | 0.347185144 | None | None | N |
| V/C | 0.7938 | likely_pathogenic | 0.7643 | pathogenic | -0.537 | Destabilizing | 0.935 | D | 0.379 | neutral | None | None | None | None | N |
| V/D | 0.3512 | ambiguous | 0.3664 | ambiguous | -0.459 | Destabilizing | 0.317 | N | 0.422 | neutral | N | 0.347129876 | None | None | N |
| V/E | 0.2974 | likely_benign | 0.3066 | benign | -0.597 | Destabilizing | 0.38 | N | 0.41 | neutral | None | None | None | None | N |
| V/F | 0.1433 | likely_benign | 0.1179 | benign | -0.697 | Destabilizing | 0.062 | N | 0.416 | neutral | N | 0.347017249 | None | None | N |
| V/G | 0.2855 | likely_benign | 0.2775 | benign | -0.34 | Destabilizing | 0.117 | N | 0.4 | neutral | N | 0.326164288 | None | None | N |
| V/H | 0.5932 | likely_pathogenic | 0.5702 | pathogenic | 0.002 | Stabilizing | 0.698 | D | 0.397 | neutral | None | None | None | None | N |
| V/I | 0.0666 | likely_benign | 0.0625 | benign | -0.225 | Destabilizing | None | N | 0.223 | neutral | N | 0.349494718 | None | None | N |
| V/K | 0.4418 | ambiguous | 0.4714 | ambiguous | -0.318 | Destabilizing | 0.38 | N | 0.412 | neutral | None | None | None | None | N |
| V/L | 0.1668 | likely_benign | 0.1518 | benign | -0.225 | Destabilizing | None | N | 0.163 | neutral | N | 0.347652149 | None | None | N |
| V/M | 0.1491 | likely_benign | 0.132 | benign | -0.329 | Destabilizing | 0.38 | N | 0.403 | neutral | None | None | None | None | N |
| V/N | 0.2665 | likely_benign | 0.2427 | benign | -0.016 | Destabilizing | 0.38 | N | 0.429 | neutral | None | None | None | None | N |
| V/P | 0.6355 | likely_pathogenic | 0.5223 | ambiguous | -0.207 | Destabilizing | 0.555 | D | 0.418 | neutral | None | None | None | None | N |
| V/Q | 0.3758 | ambiguous | 0.3549 | ambiguous | -0.302 | Destabilizing | 0.555 | D | 0.411 | neutral | None | None | None | None | N |
| V/R | 0.3908 | ambiguous | 0.4414 | ambiguous | 0.206 | Stabilizing | 0.38 | N | 0.431 | neutral | None | None | None | None | N |
| V/S | 0.2884 | likely_benign | 0.2601 | benign | -0.284 | Destabilizing | 0.081 | N | 0.359 | neutral | None | None | None | None | N |
| V/T | 0.3012 | likely_benign | 0.2599 | benign | -0.334 | Destabilizing | 0.001 | N | 0.153 | neutral | None | None | None | None | N |
| V/W | 0.7108 | likely_pathogenic | 0.7264 | pathogenic | -0.769 | Destabilizing | 0.824 | D | 0.413 | neutral | None | None | None | None | N |
| V/Y | 0.4341 | ambiguous | 0.4426 | ambiguous | -0.462 | Destabilizing | 0.001 | N | 0.229 | 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.