Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29001 | 87226;87227;87228 | chr2:178558458;178558457;178558456 | chr2:179423185;179423184;179423183 |
| N2AB | 27360 | 82303;82304;82305 | chr2:178558458;178558457;178558456 | chr2:179423185;179423184;179423183 |
| N2A | 26433 | 79522;79523;79524 | chr2:178558458;178558457;178558456 | chr2:179423185;179423184;179423183 |
| N2B | 19936 | 60031;60032;60033 | chr2:178558458;178558457;178558456 | chr2:179423185;179423184;179423183 |
| Novex-1 | 20061 | 60406;60407;60408 | chr2:178558458;178558457;178558456 | chr2:179423185;179423184;179423183 |
| Novex-2 | 20128 | 60607;60608;60609 | chr2:178558458;178558457;178558456 | chr2:179423185;179423184;179423183 |
| 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/I | rs750591986  |
-0.218 | 0.001 | N | 0.177 | 0.061 | 0.201204373187 | gnomAD-2.1.1 | 2.86E-05 | None | None | None | None | N | None | 4.13E-05 | 2.83E-05 | None | 9.68E-05 | 0 | None | 0 | None | 0 | 3.91E-05 | 0 |
| V/I | rs750591986 |
-0.218 | 0.001 | N | 0.177 | 0.061 | 0.201204373187 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs750591986 |
-0.218 | 0.001 | N | 0.177 | 0.061 | 0.201204373187 | gnomAD-4.0.0 | 1.11547E-05 | None | None | None | None | N | None | 1.33461E-05 | 3.33522E-05 | None | 6.75676E-05 | 0 | None | 0 | 0 | 1.10184E-05 | 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 | 0.1011 | likely_benign | 0.1064 | benign | -1.023 | Destabilizing | 0.027 | N | 0.487 | neutral | N | 0.498759677 | None | None | N |
| V/C | 0.4734 | ambiguous | 0.4916 | ambiguous | -0.584 | Destabilizing | 0.824 | D | 0.591 | neutral | None | None | None | None | N |
| V/D | 0.2226 | likely_benign | 0.234 | benign | -0.842 | Destabilizing | 0.317 | N | 0.667 | neutral | N | 0.513401056 | None | None | N |
| V/E | 0.1712 | likely_benign | 0.1762 | benign | -0.926 | Destabilizing | 0.38 | N | 0.646 | neutral | None | None | None | None | N |
| V/F | 0.1345 | likely_benign | 0.1422 | benign | -1.077 | Destabilizing | 0.541 | D | 0.613 | neutral | N | 0.488031462 | None | None | N |
| V/G | 0.1836 | likely_benign | 0.1957 | benign | -1.243 | Destabilizing | 0.317 | N | 0.635 | neutral | N | 0.476421667 | None | None | N |
| V/H | 0.2692 | likely_benign | 0.2835 | benign | -0.842 | Destabilizing | 0.935 | D | 0.678 | prob.neutral | None | None | None | None | N |
| V/I | 0.0661 | likely_benign | 0.0669 | benign | -0.561 | Destabilizing | 0.001 | N | 0.177 | neutral | N | 0.493025784 | None | None | N |
| V/K | 0.1791 | likely_benign | 0.1917 | benign | -0.814 | Destabilizing | 0.38 | N | 0.647 | neutral | None | None | None | None | N |
| V/L | 0.1178 | likely_benign | 0.1205 | benign | -0.561 | Destabilizing | 0.023 | N | 0.385 | neutral | N | 0.474613381 | None | None | N |
| V/M | 0.0887 | likely_benign | 0.0912 | benign | -0.29 | Destabilizing | 0.38 | N | 0.538 | neutral | None | None | None | None | N |
| V/N | 0.1385 | likely_benign | 0.1461 | benign | -0.45 | Destabilizing | 0.38 | N | 0.673 | neutral | None | None | None | None | N |
| V/P | 0.4309 | ambiguous | 0.4843 | ambiguous | -0.679 | Destabilizing | 0.555 | D | 0.667 | neutral | None | None | None | None | N |
| V/Q | 0.1725 | likely_benign | 0.1792 | benign | -0.715 | Destabilizing | 0.555 | D | 0.664 | neutral | None | None | None | None | N |
| V/R | 0.1618 | likely_benign | 0.1746 | benign | -0.231 | Destabilizing | 0.38 | N | 0.683 | prob.neutral | None | None | None | None | N |
| V/S | 0.1154 | likely_benign | 0.1195 | benign | -0.865 | Destabilizing | 0.081 | N | 0.596 | neutral | None | None | None | None | N |
| V/T | 0.0744 | likely_benign | 0.0782 | benign | -0.847 | Destabilizing | None | N | 0.19 | neutral | None | None | None | None | N |
| V/W | 0.6048 | likely_pathogenic | 0.6357 | pathogenic | -1.187 | Destabilizing | 0.935 | D | 0.731 | prob.delet. | None | None | None | None | N |
| V/Y | 0.3387 | likely_benign | 0.3533 | ambiguous | -0.906 | Destabilizing | 0.555 | D | 0.621 | 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.