Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32131 | 96616;96617;96618 | chr2:178543582;178543581;178543580 | chr2:179408309;179408308;179408307 |
| N2AB | 30490 | 91693;91694;91695 | chr2:178543582;178543581;178543580 | chr2:179408309;179408308;179408307 |
| N2A | 29563 | 88912;88913;88914 | chr2:178543582;178543581;178543580 | chr2:179408309;179408308;179408307 |
| N2B | 23066 | 69421;69422;69423 | chr2:178543582;178543581;178543580 | chr2:179408309;179408308;179408307 |
| Novex-1 | 23191 | 69796;69797;69798 | chr2:178543582;178543581;178543580 | chr2:179408309;179408308;179408307 |
| Novex-2 | 23258 | 69997;69998;69999 | chr2:178543582;178543581;178543580 | chr2:179408309;179408308;179408307 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs978818932  |
None | None | N | 0.231 | 0.114 | 0.492267288202 | gnomAD-4.0.0 | 2.74698E-06 | None | None | None | None | I | None | 2.98846E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69877E-06 | 0 | 0 |
| I/V | rs567606606 |
-0.094 | 0.002 | N | 0.096 | 0.073 | 0.343334270461 | gnomAD-2.1.1 | 4.1E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.28E-05 | None | 0 | 0 | 0 |
| I/V | rs567606606 |
-0.094 | 0.002 | N | 0.096 | 0.073 | 0.343334270461 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07125E-04 | 0 |
| I/V | rs567606606 |
-0.094 | 0.002 | N | 0.096 | 0.073 | 0.343334270461 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| I/V | rs567606606 |
-0.094 | 0.002 | N | 0.096 | 0.073 | 0.343334270461 | gnomAD-4.0.0 | 2.57988E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.68147E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.2288 | likely_benign | 0.249 | benign | -0.602 | Destabilizing | 0.035 | N | 0.351 | neutral | None | None | None | None | I |
| I/C | 0.7062 | likely_pathogenic | 0.7395 | pathogenic | -0.536 | Destabilizing | 0.824 | D | 0.35 | neutral | None | None | None | None | I |
| I/D | 0.6854 | likely_pathogenic | 0.6736 | pathogenic | -0.082 | Destabilizing | 0.38 | N | 0.479 | neutral | None | None | None | None | I |
| I/E | 0.6101 | likely_pathogenic | 0.6206 | pathogenic | -0.184 | Destabilizing | 0.38 | N | 0.478 | neutral | None | None | None | None | I |
| I/F | 0.2167 | likely_benign | 0.2592 | benign | -0.682 | Destabilizing | 0.317 | N | 0.334 | neutral | N | 0.431377105 | None | None | I |
| I/G | 0.6223 | likely_pathogenic | 0.6476 | pathogenic | -0.757 | Destabilizing | 0.38 | N | 0.449 | neutral | None | None | None | None | I |
| I/H | 0.58 | likely_pathogenic | 0.6062 | pathogenic | -0.163 | Destabilizing | 0.935 | D | 0.431 | neutral | None | None | None | None | I |
| I/K | 0.5371 | ambiguous | 0.5596 | ambiguous | -0.265 | Destabilizing | 0.38 | N | 0.461 | neutral | None | None | None | None | I |
| I/L | 0.1087 | likely_benign | 0.1129 | benign | -0.321 | Destabilizing | None | N | 0.08 | neutral | N | 0.46165994 | None | None | I |
| I/M | 0.1006 | likely_benign | 0.1036 | benign | -0.296 | Destabilizing | 0.317 | N | 0.359 | neutral | N | 0.492502922 | None | None | I |
| I/N | 0.2468 | likely_benign | 0.232 | benign | -0.018 | Destabilizing | 0.317 | N | 0.475 | neutral | N | 0.416503653 | None | None | I |
| I/P | 0.869 | likely_pathogenic | 0.8847 | pathogenic | -0.381 | Destabilizing | 0.555 | D | 0.475 | neutral | None | None | None | None | I |
| I/Q | 0.5041 | ambiguous | 0.5129 | ambiguous | -0.26 | Destabilizing | 0.555 | D | 0.456 | neutral | None | None | None | None | I |
| I/R | 0.4297 | ambiguous | 0.4368 | ambiguous | 0.253 | Stabilizing | 0.38 | N | 0.471 | neutral | None | None | None | None | I |
| I/S | 0.2351 | likely_benign | 0.2407 | benign | -0.471 | Destabilizing | 0.062 | N | 0.44 | neutral | N | 0.383641873 | None | None | I |
| I/T | 0.1183 | likely_benign | 0.1462 | benign | -0.466 | Destabilizing | None | N | 0.231 | neutral | N | 0.451232302 | None | None | I |
| I/V | 0.0623 | likely_benign | 0.0667 | benign | -0.381 | Destabilizing | 0.002 | N | 0.096 | neutral | N | 0.41881324 | None | None | I |
| I/W | 0.7803 | likely_pathogenic | 0.8135 | pathogenic | -0.698 | Destabilizing | 0.935 | D | 0.561 | neutral | None | None | None | None | I |
| I/Y | 0.5728 | likely_pathogenic | 0.5901 | pathogenic | -0.433 | Destabilizing | 0.555 | D | 0.365 | 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.