Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16311 | 49156;49157;49158 | chr2:178614583;178614582;178614581 | chr2:179479310;179479309;179479308 |
| N2AB | 14670 | 44233;44234;44235 | chr2:178614583;178614582;178614581 | chr2:179479310;179479309;179479308 |
| N2A | 13743 | 41452;41453;41454 | chr2:178614583;178614582;178614581 | chr2:179479310;179479309;179479308 |
| N2B | 7246 | 21961;21962;21963 | chr2:178614583;178614582;178614581 | chr2:179479310;179479309;179479308 |
| Novex-1 | 7371 | 22336;22337;22338 | chr2:178614583;178614582;178614581 | chr2:179479310;179479309;179479308 |
| Novex-2 | 7438 | 22537;22538;22539 | chr2:178614583;178614582;178614581 | chr2:179479310;179479309;179479308 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/H | rs763372996  |
0.066 | 1.0 | N | 0.657 | 0.376 | 0.306695030598 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.57E-05 | 0 |
| P/H | rs763372996 |
0.066 | 1.0 | N | 0.657 | 0.376 | 0.306695030598 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.89E-05 | 0 | 0 |
| P/H | rs763372996 |
0.066 | 1.0 | N | 0.657 | 0.376 | 0.306695030598 | gnomAD-4.0.0 | 1.73673E-05 | None | None | None | None | N | None | 1.33772E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.12018E-05 | 0 | 3.20616E-05 |
| P/L | None | None | 0.999 | N | 0.663 | 0.38 | 0.379366414296 | gnomAD-4.0.0 | 6.84726E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99896E-07 | 0 | 0 |
| P/S | None | None | 0.998 | N | 0.621 | 0.293 | 0.229264304666 | gnomAD-4.0.0 | 1.59404E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43369E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.1109 | likely_benign | 0.0996 | benign | -0.376 | Destabilizing | 0.996 | D | 0.537 | neutral | N | 0.446565363 | None | None | N |
| P/C | 0.681 | likely_pathogenic | 0.6233 | pathogenic | -0.76 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| P/D | 0.5041 | ambiguous | 0.453 | ambiguous | -0.529 | Destabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | N |
| P/E | 0.3875 | ambiguous | 0.3273 | benign | -0.638 | Destabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | N |
| P/F | 0.7074 | likely_pathogenic | 0.6412 | pathogenic | -0.691 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| P/G | 0.3273 | likely_benign | 0.2925 | benign | -0.456 | Destabilizing | 1.0 | D | 0.616 | neutral | None | None | None | None | N |
| P/H | 0.3399 | likely_benign | 0.2912 | benign | -0.007 | Destabilizing | 1.0 | D | 0.657 | neutral | N | 0.439671722 | None | None | N |
| P/I | 0.5415 | ambiguous | 0.4746 | ambiguous | -0.304 | Destabilizing | 0.999 | D | 0.697 | prob.neutral | None | None | None | None | N |
| P/K | 0.414 | ambiguous | 0.3467 | ambiguous | -0.488 | Destabilizing | 1.0 | D | 0.656 | neutral | None | None | None | None | N |
| P/L | 0.1969 | likely_benign | 0.1677 | benign | -0.304 | Destabilizing | 0.999 | D | 0.663 | neutral | N | 0.450953591 | None | None | N |
| P/M | 0.4743 | ambiguous | 0.4049 | ambiguous | -0.59 | Destabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | N |
| P/N | 0.4188 | ambiguous | 0.3636 | ambiguous | -0.294 | Destabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | N |
| P/Q | 0.2449 | likely_benign | 0.203 | benign | -0.513 | Destabilizing | 1.0 | D | 0.675 | neutral | None | None | None | None | N |
| P/R | 0.3019 | likely_benign | 0.2541 | benign | None | Stabilizing | 0.999 | D | 0.674 | neutral | N | 0.456087684 | None | None | N |
| P/S | 0.183 | likely_benign | 0.1598 | benign | -0.569 | Destabilizing | 0.998 | D | 0.621 | neutral | N | 0.442182998 | None | None | N |
| P/T | 0.1931 | likely_benign | 0.163 | benign | -0.588 | Destabilizing | 0.884 | D | 0.345 | neutral | N | 0.444384011 | None | None | N |
| P/V | 0.3774 | ambiguous | 0.3241 | benign | -0.299 | Destabilizing | 0.999 | D | 0.61 | neutral | None | None | None | None | N |
| P/W | 0.8181 | likely_pathogenic | 0.7682 | pathogenic | -0.763 | Destabilizing | 1.0 | D | 0.702 | prob.neutral | None | None | None | None | N |
| P/Y | 0.6441 | likely_pathogenic | 0.5782 | pathogenic | -0.489 | Destabilizing | 1.0 | D | 0.691 | 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.