Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25746 | 77461;77462;77463 | chr2:178568896;178568895;178568894 | chr2:179433623;179433622;179433621 |
| N2AB | 24105 | 72538;72539;72540 | chr2:178568896;178568895;178568894 | chr2:179433623;179433622;179433621 |
| N2A | 23178 | 69757;69758;69759 | chr2:178568896;178568895;178568894 | chr2:179433623;179433622;179433621 |
| N2B | 16681 | 50266;50267;50268 | chr2:178568896;178568895;178568894 | chr2:179433623;179433622;179433621 |
| Novex-1 | 16806 | 50641;50642;50643 | chr2:178568896;178568895;178568894 | chr2:179433623;179433622;179433621 |
| Novex-2 | 16873 | 50842;50843;50844 | chr2:178568896;178568895;178568894 | chr2:179433623;179433622;179433621 |
| 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/L | None | None | 0.989 | N | 0.571 | 0.403 | 0.485991781493 | gnomAD-4.0.0 | 6.84455E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99617E-07 | 0 | 0 |
| S/P | None | None | 0.999 | N | 0.703 | 0.367 | 0.307016933798 | gnomAD-4.0.0 | 1.20033E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.31251E-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 | 0.0864 | likely_benign | 0.0836 | benign | -0.604 | Destabilizing | 0.973 | D | 0.412 | neutral | N | 0.468994131 | None | None | N |
| S/C | 0.1468 | likely_benign | 0.1354 | benign | -0.362 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| S/D | 0.5105 | ambiguous | 0.4463 | ambiguous | -0.001 | Destabilizing | 0.996 | D | 0.551 | neutral | None | None | None | None | N |
| S/E | 0.5118 | ambiguous | 0.4413 | ambiguous | -0.05 | Destabilizing | 0.996 | D | 0.549 | neutral | None | None | None | None | N |
| S/F | 0.2331 | likely_benign | 0.2059 | benign | -0.91 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | N |
| S/G | 0.1175 | likely_benign | 0.1101 | benign | -0.8 | Destabilizing | 0.996 | D | 0.492 | neutral | None | None | None | None | N |
| S/H | 0.3781 | ambiguous | 0.3314 | benign | -1.208 | Destabilizing | 1.0 | D | 0.686 | prob.neutral | None | None | None | None | N |
| S/I | 0.1527 | likely_benign | 0.1375 | benign | -0.204 | Destabilizing | 0.998 | D | 0.723 | prob.delet. | None | None | None | None | N |
| S/K | 0.6648 | likely_pathogenic | 0.5782 | pathogenic | -0.71 | Destabilizing | 0.996 | D | 0.545 | neutral | None | None | None | None | N |
| S/L | 0.1009 | likely_benign | 0.0954 | benign | -0.204 | Destabilizing | 0.989 | D | 0.571 | neutral | N | 0.477960331 | None | None | N |
| S/M | 0.1588 | likely_benign | 0.1454 | benign | 0.023 | Stabilizing | 1.0 | D | 0.688 | prob.neutral | None | None | None | None | N |
| S/N | 0.1442 | likely_benign | 0.1267 | benign | -0.487 | Destabilizing | 0.996 | D | 0.535 | neutral | None | None | None | None | N |
| S/P | 0.8928 | likely_pathogenic | 0.8717 | pathogenic | -0.305 | Destabilizing | 0.999 | D | 0.703 | prob.neutral | N | 0.479433407 | None | None | N |
| S/Q | 0.4602 | ambiguous | 0.402 | ambiguous | -0.676 | Destabilizing | 1.0 | D | 0.657 | neutral | None | None | None | None | N |
| S/R | 0.6173 | likely_pathogenic | 0.5424 | ambiguous | -0.489 | Destabilizing | 0.999 | D | 0.705 | prob.neutral | None | None | None | None | N |
| S/T | 0.0684 | likely_benign | 0.0653 | benign | -0.561 | Destabilizing | 0.543 | D | 0.287 | neutral | N | 0.406945595 | None | None | N |
| S/V | 0.1478 | likely_benign | 0.1336 | benign | -0.305 | Destabilizing | 0.998 | D | 0.641 | neutral | None | None | None | None | N |
| S/W | 0.4274 | ambiguous | 0.3848 | ambiguous | -0.893 | Destabilizing | 1.0 | D | 0.736 | prob.delet. | None | None | None | None | N |
| S/Y | 0.2283 | likely_benign | 0.1992 | benign | -0.649 | Destabilizing | 1.0 | D | 0.705 | prob.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.