Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24494 | 73705;73706;73707 | chr2:178572652;178572651;178572650 | chr2:179437379;179437378;179437377 |
| N2AB | 22853 | 68782;68783;68784 | chr2:178572652;178572651;178572650 | chr2:179437379;179437378;179437377 |
| N2A | 21926 | 66001;66002;66003 | chr2:178572652;178572651;178572650 | chr2:179437379;179437378;179437377 |
| N2B | 15429 | 46510;46511;46512 | chr2:178572652;178572651;178572650 | chr2:179437379;179437378;179437377 |
| Novex-1 | 15554 | 46885;46886;46887 | chr2:178572652;178572651;178572650 | chr2:179437379;179437378;179437377 |
| Novex-2 | 15621 | 47086;47087;47088 | chr2:178572652;178572651;178572650 | chr2:179437379;179437378;179437377 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/G | None | None | 0.001 | N | 0.12 | 0.156 | 0.212008924253 | gnomAD-4.0.0 | 3.18607E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43472E-05 | 3.027E-05 |
| S/T | rs767397034  |
-0.561 | 0.684 | N | 0.466 | 0.156 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| S/T | rs767397034 |
-0.561 | 0.684 | N | 0.466 | 0.156 | None | gnomAD-4.0.0 | 2.73831E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 3.47584E-04 | 1.79963E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1087 | likely_benign | 0.1015 | benign | -0.743 | Destabilizing | 0.016 | N | 0.142 | neutral | None | None | None | None | I |
| S/C | 0.1693 | likely_benign | 0.1606 | benign | -0.528 | Destabilizing | 0.994 | D | 0.495 | neutral | D | 0.523843985 | None | None | I |
| S/D | 0.9409 | likely_pathogenic | 0.9589 | pathogenic | -0.052 | Destabilizing | 0.742 | D | 0.418 | neutral | None | None | None | None | I |
| S/E | 0.9471 | likely_pathogenic | 0.9562 | pathogenic | -0.091 | Destabilizing | 0.742 | D | 0.436 | neutral | None | None | None | None | I |
| S/F | 0.74 | likely_pathogenic | 0.7567 | pathogenic | -1.107 | Destabilizing | 0.953 | D | 0.57 | neutral | None | None | None | None | I |
| S/G | 0.1236 | likely_benign | 0.1325 | benign | -0.935 | Destabilizing | 0.001 | N | 0.12 | neutral | N | 0.514975216 | None | None | I |
| S/H | 0.8334 | likely_pathogenic | 0.8529 | pathogenic | -1.441 | Destabilizing | 0.02 | N | 0.275 | neutral | None | None | None | None | I |
| S/I | 0.6894 | likely_pathogenic | 0.7047 | pathogenic | -0.349 | Destabilizing | 0.939 | D | 0.567 | neutral | N | 0.516589056 | None | None | I |
| S/K | 0.9734 | likely_pathogenic | 0.9795 | pathogenic | -0.639 | Destabilizing | 0.742 | D | 0.415 | neutral | None | None | None | None | I |
| S/L | 0.3405 | ambiguous | 0.3564 | ambiguous | -0.349 | Destabilizing | 0.742 | D | 0.521 | neutral | None | None | None | None | I |
| S/M | 0.4362 | ambiguous | 0.4771 | ambiguous | 0.001 | Stabilizing | 0.996 | D | 0.505 | neutral | None | None | None | None | I |
| S/N | 0.5169 | ambiguous | 0.5851 | pathogenic | -0.52 | Destabilizing | 0.684 | D | 0.453 | neutral | N | 0.504218793 | None | None | I |
| S/P | 0.9643 | likely_pathogenic | 0.9571 | pathogenic | -0.449 | Destabilizing | 0.984 | D | 0.519 | neutral | None | None | None | None | I |
| S/Q | 0.8791 | likely_pathogenic | 0.8937 | pathogenic | -0.749 | Destabilizing | 0.91 | D | 0.474 | neutral | None | None | None | None | I |
| S/R | 0.9482 | likely_pathogenic | 0.9556 | pathogenic | -0.489 | Destabilizing | 0.884 | D | 0.509 | neutral | N | 0.497470843 | None | None | I |
| S/T | 0.1222 | likely_benign | 0.1571 | benign | -0.616 | Destabilizing | 0.684 | D | 0.466 | neutral | N | 0.492906433 | None | None | I |
| S/V | 0.6023 | likely_pathogenic | 0.6187 | pathogenic | -0.449 | Destabilizing | 0.742 | D | 0.541 | neutral | None | None | None | None | I |
| S/W | 0.8865 | likely_pathogenic | 0.8839 | pathogenic | -1.037 | Destabilizing | 0.996 | D | 0.603 | neutral | None | None | None | None | I |
| S/Y | 0.7268 | likely_pathogenic | 0.7451 | pathogenic | -0.785 | Destabilizing | 0.835 | D | 0.573 | 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.