Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14186 | 42781;42782;42783 | chr2:178633943;178633942;178633941 | chr2:179498670;179498669;179498668 |
| N2AB | 12545 | 37858;37859;37860 | chr2:178633943;178633942;178633941 | chr2:179498670;179498669;179498668 |
| N2A | 11618 | 35077;35078;35079 | chr2:178633943;178633942;178633941 | chr2:179498670;179498669;179498668 |
| N2B | 5121 | 15586;15587;15588 | chr2:178633943;178633942;178633941 | chr2:179498670;179498669;179498668 |
| Novex-1 | 5246 | 15961;15962;15963 | chr2:178633943;178633942;178633941 | chr2:179498670;179498669;179498668 |
| Novex-2 | 5313 | 16162;16163;16164 | chr2:178633943;178633942;178633941 | chr2:179498670;179498669;179498668 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/K | rs369771893  |
-0.619 | 1.0 | N | 0.653 | 0.427 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| T/K | rs369771893 |
-0.619 | 1.0 | N | 0.653 | 0.427 | None | gnomAD-4.0.0 | 2.47945E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.39104E-06 | 0 | 0 |
| T/P | rs1187615662 |
-0.348 | 1.0 | N | 0.625 | 0.486 | 0.32471235697 | gnomAD-4.0.0 | 1.59192E-06 | None | None | None | None | N | None | 0 | 2.28676E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/R | None | None | 1.0 | N | 0.626 | 0.417 | 0.324436698001 | gnomAD-4.0.0 | 6.84335E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99616E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1744 | likely_benign | 0.19 | benign | -0.541 | Destabilizing | 0.999 | D | 0.447 | neutral | N | 0.473659774 | None | None | N |
| T/C | 0.7641 | likely_pathogenic | 0.7911 | pathogenic | -0.333 | Destabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | N |
| T/D | 0.5679 | likely_pathogenic | 0.6194 | pathogenic | 0.263 | Stabilizing | 1.0 | D | 0.65 | neutral | None | None | None | None | N |
| T/E | 0.5399 | ambiguous | 0.5944 | pathogenic | 0.229 | Stabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | N |
| T/F | 0.474 | ambiguous | 0.5254 | ambiguous | -0.757 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| T/G | 0.4177 | ambiguous | 0.4601 | ambiguous | -0.749 | Destabilizing | 1.0 | D | 0.658 | neutral | None | None | None | None | N |
| T/H | 0.3946 | ambiguous | 0.4405 | ambiguous | -1.053 | Destabilizing | 1.0 | D | 0.704 | prob.neutral | None | None | None | None | N |
| T/I | 0.4652 | ambiguous | 0.4868 | ambiguous | -0.097 | Destabilizing | 1.0 | D | 0.641 | neutral | N | 0.516176302 | None | None | N |
| T/K | 0.2961 | likely_benign | 0.3662 | ambiguous | -0.487 | Destabilizing | 1.0 | D | 0.653 | neutral | N | 0.414243353 | None | None | N |
| T/L | 0.2283 | likely_benign | 0.2386 | benign | -0.097 | Destabilizing | 0.999 | D | 0.578 | neutral | None | None | None | None | N |
| T/M | 0.1425 | likely_benign | 0.1547 | benign | 0.087 | Stabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | N |
| T/N | 0.1925 | likely_benign | 0.2099 | benign | -0.318 | Destabilizing | 1.0 | D | 0.649 | neutral | None | None | None | None | N |
| T/P | 0.4122 | ambiguous | 0.4995 | ambiguous | -0.213 | Destabilizing | 1.0 | D | 0.625 | neutral | N | 0.516377853 | None | None | N |
| T/Q | 0.3917 | ambiguous | 0.4351 | ambiguous | -0.501 | Destabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | N |
| T/R | 0.2714 | likely_benign | 0.3319 | benign | -0.279 | Destabilizing | 1.0 | D | 0.626 | neutral | N | 0.424960143 | None | None | N |
| T/S | 0.2068 | likely_benign | 0.2248 | benign | -0.607 | Destabilizing | 0.999 | D | 0.483 | neutral | N | 0.434914561 | None | None | N |
| T/V | 0.3654 | ambiguous | 0.3849 | ambiguous | -0.213 | Destabilizing | 0.999 | D | 0.517 | neutral | None | None | None | None | N |
| T/W | 0.7438 | likely_pathogenic | 0.799 | pathogenic | -0.707 | Destabilizing | 1.0 | D | 0.706 | prob.neutral | None | None | None | None | N |
| T/Y | 0.4394 | ambiguous | 0.5197 | ambiguous | -0.458 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | 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.