Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31366 | 94321;94322;94323 | chr2:178547530;178547529;178547528 | chr2:179412257;179412256;179412255 |
| N2AB | 29725 | 89398;89399;89400 | chr2:178547530;178547529;178547528 | chr2:179412257;179412256;179412255 |
| N2A | 28798 | 86617;86618;86619 | chr2:178547530;178547529;178547528 | chr2:179412257;179412256;179412255 |
| N2B | 22301 | 67126;67127;67128 | chr2:178547530;178547529;178547528 | chr2:179412257;179412256;179412255 |
| Novex-1 | 22426 | 67501;67502;67503 | chr2:178547530;178547529;178547528 | chr2:179412257;179412256;179412255 |
| Novex-2 | 22493 | 67702;67703;67704 | chr2:178547530;178547529;178547528 | chr2:179412257;179412256;179412255 |
| 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/A | rs1369343605  |
-0.706 | 0.928 | N | 0.451 | 0.487 | 0.322230723748 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| T/A | rs1369343605 |
-0.706 | 0.928 | N | 0.451 | 0.487 | 0.322230723748 | gnomAD-4.0.0 | 2.05276E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69842E-06 | 0 | 0 |
| T/I | None | None | 0.085 | N | 0.356 | 0.438 | 0.286081765059 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| T/P | None | None | 0.996 | N | 0.729 | 0.475 | 0.379881503574 | gnomAD-4.0.0 | 6.84255E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.87357E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1484 | likely_benign | 0.1347 | benign | -0.842 | Destabilizing | 0.928 | D | 0.451 | neutral | N | 0.497982189 | None | None | N |
| T/C | 0.3031 | likely_benign | 0.2501 | benign | -0.471 | Destabilizing | 0.999 | D | 0.733 | prob.delet. | None | None | None | None | N |
| T/D | 0.6574 | likely_pathogenic | 0.6041 | pathogenic | -0.114 | Destabilizing | 0.997 | D | 0.697 | prob.neutral | None | None | None | None | N |
| T/E | 0.5843 | likely_pathogenic | 0.5187 | ambiguous | 0.027 | Stabilizing | 0.997 | D | 0.695 | prob.neutral | None | None | None | None | N |
| T/F | 0.6212 | likely_pathogenic | 0.5739 | pathogenic | -0.769 | Destabilizing | 0.983 | D | 0.737 | prob.delet. | None | None | None | None | N |
| T/G | 0.3129 | likely_benign | 0.2603 | benign | -1.196 | Destabilizing | 0.992 | D | 0.648 | neutral | None | None | None | None | N |
| T/H | 0.3481 | ambiguous | 0.3071 | benign | -1.165 | Destabilizing | 0.999 | D | 0.745 | deleterious | None | None | None | None | N |
| T/I | 0.5775 | likely_pathogenic | 0.5049 | ambiguous | 0.056 | Stabilizing | 0.085 | N | 0.356 | neutral | N | 0.503159976 | None | None | N |
| T/K | 0.2252 | likely_benign | 0.1905 | benign | -0.057 | Destabilizing | 0.992 | D | 0.697 | prob.neutral | None | None | None | None | N |
| T/L | 0.1628 | likely_benign | 0.1338 | benign | 0.056 | Stabilizing | 0.745 | D | 0.498 | neutral | None | None | None | None | N |
| T/M | 0.1268 | likely_benign | 0.1178 | benign | -0.075 | Destabilizing | 0.996 | D | 0.741 | deleterious | None | None | None | None | N |
| T/N | 0.1236 | likely_benign | 0.1171 | benign | -0.526 | Destabilizing | 0.996 | D | 0.644 | neutral | N | 0.470736901 | None | None | N |
| T/P | 0.0913 | likely_benign | 0.0793 | benign | -0.211 | Destabilizing | 0.996 | D | 0.729 | prob.delet. | N | 0.466533393 | None | None | N |
| T/Q | 0.2523 | likely_benign | 0.2121 | benign | -0.391 | Destabilizing | 0.997 | D | 0.751 | deleterious | None | None | None | None | N |
| T/R | 0.1843 | likely_benign | 0.1592 | benign | -0.131 | Destabilizing | 0.997 | D | 0.737 | prob.delet. | None | None | None | None | N |
| T/S | 0.1595 | likely_benign | 0.1485 | benign | -0.904 | Destabilizing | 0.963 | D | 0.412 | neutral | N | 0.493107117 | None | None | N |
| T/V | 0.4 | ambiguous | 0.3295 | benign | -0.211 | Destabilizing | 0.547 | D | 0.461 | neutral | None | None | None | None | N |
| T/W | 0.837 | likely_pathogenic | 0.7995 | pathogenic | -0.802 | Destabilizing | 0.999 | D | 0.733 | prob.delet. | None | None | None | None | N |
| T/Y | 0.5562 | ambiguous | 0.5203 | ambiguous | -0.426 | Destabilizing | 0.992 | D | 0.75 | deleterious | 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.