Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14487 | 43684;43685;43686 | chr2:178632547;178632546;178632545 | chr2:179497274;179497273;179497272 |
| N2AB | 12846 | 38761;38762;38763 | chr2:178632547;178632546;178632545 | chr2:179497274;179497273;179497272 |
| N2A | 11919 | 35980;35981;35982 | chr2:178632547;178632546;178632545 | chr2:179497274;179497273;179497272 |
| N2B | 5422 | 16489;16490;16491 | chr2:178632547;178632546;178632545 | chr2:179497274;179497273;179497272 |
| Novex-1 | 5547 | 16864;16865;16866 | chr2:178632547;178632546;178632545 | chr2:179497274;179497273;179497272 |
| Novex-2 | 5614 | 17065;17066;17067 | chr2:178632547;178632546;178632545 | chr2:179497274;179497273;179497272 |
| 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/N | rs770233190  |
-0.183 | 0.994 | D | 0.577 | 0.466 | None | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 1.14784E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/N | rs770233190 |
-0.183 | 0.994 | D | 0.577 | 0.466 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| S/N | rs770233190 |
-0.183 | 0.994 | D | 0.577 | 0.466 | None | gnomAD-4.0.0 | 2.4796E-05 | None | None | None | None | N | None | 1.33543E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 3.22155E-05 | 0 | 1.60205E-05 |
| S/R | rs2059935679 |
None | 0.998 | D | 0.739 | 0.624 | 0.547512163748 | gnomAD-4.0.0 | 1.59266E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.88303E-05 | 0 | 0 | 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 | 0.1033 | likely_benign | 0.1015 | benign | -0.662 | Destabilizing | 0.98 | D | 0.451 | neutral | None | None | None | None | N |
| S/C | 0.1983 | likely_benign | 0.1671 | benign | -0.487 | Destabilizing | 1.0 | D | 0.72 | prob.delet. | D | 0.667608389 | None | None | N |
| S/D | 0.7009 | likely_pathogenic | 0.6914 | pathogenic | -0.53 | Destabilizing | 0.996 | D | 0.591 | neutral | None | None | None | None | N |
| S/E | 0.6807 | likely_pathogenic | 0.6741 | pathogenic | -0.53 | Destabilizing | 0.996 | D | 0.589 | neutral | None | None | None | None | N |
| S/F | 0.2719 | likely_benign | 0.2501 | benign | -0.771 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | N |
| S/G | 0.2081 | likely_benign | 0.1876 | benign | -0.924 | Destabilizing | 0.994 | D | 0.575 | neutral | D | 0.66828037 | None | None | N |
| S/H | 0.5275 | ambiguous | 0.4925 | ambiguous | -1.404 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | N |
| S/I | 0.2527 | likely_benign | 0.2557 | benign | -0.073 | Destabilizing | 0.997 | D | 0.725 | prob.delet. | D | 0.63042512 | None | None | N |
| S/K | 0.7969 | likely_pathogenic | 0.7946 | pathogenic | -0.823 | Destabilizing | 0.996 | D | 0.587 | neutral | None | None | None | None | N |
| S/L | 0.1598 | likely_benign | 0.1555 | benign | -0.073 | Destabilizing | 0.992 | D | 0.648 | neutral | None | None | None | None | N |
| S/M | 0.288 | likely_benign | 0.2766 | benign | 0.237 | Stabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | N |
| S/N | 0.2988 | likely_benign | 0.288 | benign | -0.79 | Destabilizing | 0.994 | D | 0.577 | neutral | D | 0.629594075 | None | None | N |
| S/P | 0.8334 | likely_pathogenic | 0.7844 | pathogenic | -0.235 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| S/Q | 0.6662 | likely_pathogenic | 0.6438 | pathogenic | -0.952 | Destabilizing | 1.0 | D | 0.664 | neutral | None | None | None | None | N |
| S/R | 0.6858 | likely_pathogenic | 0.6734 | pathogenic | -0.687 | Destabilizing | 0.998 | D | 0.739 | prob.delet. | D | 0.669187736 | None | None | N |
| S/T | 0.0977 | likely_benign | 0.0963 | benign | -0.772 | Destabilizing | 0.543 | D | 0.363 | neutral | D | 0.526654372 | None | None | N |
| S/V | 0.2433 | likely_benign | 0.2369 | benign | -0.235 | Destabilizing | 0.998 | D | 0.707 | prob.neutral | None | None | None | None | N |
| S/W | 0.4638 | ambiguous | 0.4021 | ambiguous | -0.77 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | N |
| S/Y | 0.2764 | likely_benign | 0.2552 | benign | -0.51 | Destabilizing | 1.0 | D | 0.731 | 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.