Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14535 | 43828;43829;43830 | chr2:178632291;178632290;178632289 | chr2:179497018;179497017;179497016 |
| N2AB | 12894 | 38905;38906;38907 | chr2:178632291;178632290;178632289 | chr2:179497018;179497017;179497016 |
| N2A | 11967 | 36124;36125;36126 | chr2:178632291;178632290;178632289 | chr2:179497018;179497017;179497016 |
| N2B | 5470 | 16633;16634;16635 | chr2:178632291;178632290;178632289 | chr2:179497018;179497017;179497016 |
| Novex-1 | 5595 | 17008;17009;17010 | chr2:178632291;178632290;178632289 | chr2:179497018;179497017;179497016 |
| Novex-2 | 5662 | 17209;17210;17211 | chr2:178632291;178632290;178632289 | chr2:179497018;179497017;179497016 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs12471771  |
-0.169 | 1.0 | D | 0.723 | 0.484 | None | gnomAD-2.1.1 | 2.14659E-02 | None | None | None | None | N | None | 2.72503E-03 | 1.64875E-01 | None | 0 | 1.05932E-04 | None | 6.75E-05 | None | 0 | 8.8E-05 | 1.61429E-02 |
| R/C | rs12471771 |
-0.169 | 1.0 | D | 0.723 | 0.484 | None | gnomAD-3.1.2 | 9.76521E-03 | None | None | None | None | N | None | 2.34367E-03 | 8.81503E-02 | 0 | 0 | 1.93798E-04 | None | 0 | 0 | 2.79478E-04 | 0 | 1.20077E-02 |
| R/C | rs12471771 |
-0.169 | 1.0 | D | 0.723 | 0.484 | None | 1000 genomes | 1.61741E-02 | None | None | None | None | N | None | 0 | 1.167E-01 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/C | rs12471771 |
-0.169 | 1.0 | D | 0.723 | 0.484 | None | gnomAD-4.0.0 | 5.45174E-03 | None | None | None | None | N | None | 2.08222E-03 | 1.39179E-01 | None | 3.39628E-05 | 4.49539E-05 | None | 0 | 0 | 5.34863E-05 | 5.53489E-05 | 4.76588E-03 |
| R/H | rs764250397 |
-0.762 | 1.0 | D | 0.743 | 0.436 | 0.435915822735 | gnomAD-2.1.1 | 2.48E-05 | None | None | None | None | N | None | 0 | 1.18441E-04 | None | 0 | 5.76E-05 | None | 0 | None | 0 | 9.12E-06 | 0 |
| R/H | rs764250397 |
-0.762 | 1.0 | D | 0.743 | 0.436 | 0.435915822735 | gnomAD-4.0.0 | 1.09771E-05 | None | None | None | None | N | None | 0 | 9.04364E-05 | None | 0 | 5.08388E-05 | None | 0 | 0 | 8.10844E-06 | 1.16918E-05 | 0 |
| R/S | rs12471771 |
-0.055 | 1.0 | D | 0.694 | 0.399 | 0.553103360211 | gnomAD-2.1.1 | 4.13E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.13E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.4757 | ambiguous | 0.4082 | ambiguous | -0.461 | Destabilizing | 0.999 | D | 0.679 | prob.neutral | None | None | None | None | N |
| R/C | 0.2246 | likely_benign | 0.2143 | benign | -0.471 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | D | 0.581888892 | None | None | N |
| R/D | 0.7592 | likely_pathogenic | 0.6982 | pathogenic | -0.23 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | N |
| R/E | 0.4008 | ambiguous | 0.3564 | ambiguous | -0.064 | Destabilizing | 0.999 | D | 0.706 | prob.neutral | None | None | None | None | N |
| R/F | 0.5934 | likely_pathogenic | 0.5491 | ambiguous | -0.083 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| R/G | 0.3978 | ambiguous | 0.3483 | ambiguous | -0.79 | Destabilizing | 1.0 | D | 0.653 | neutral | D | 0.579784788 | None | None | N |
| R/H | 0.1403 | likely_benign | 0.1236 | benign | -1.252 | Destabilizing | 1.0 | D | 0.743 | deleterious | D | 0.579784788 | None | None | N |
| R/I | 0.2405 | likely_benign | 0.2206 | benign | 0.431 | Stabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| R/K | 0.1674 | likely_benign | 0.1439 | benign | -0.389 | Destabilizing | 0.998 | D | 0.621 | neutral | None | None | None | None | N |
| R/L | 0.2521 | likely_benign | 0.2291 | benign | 0.431 | Stabilizing | 1.0 | D | 0.653 | neutral | N | 0.509217456 | None | None | N |
| R/M | 0.2905 | likely_benign | 0.2602 | benign | -0.216 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| R/N | 0.6296 | likely_pathogenic | 0.5715 | pathogenic | -0.29 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| R/P | 0.3596 | ambiguous | 0.2762 | benign | 0.154 | Stabilizing | 1.0 | D | 0.702 | prob.neutral | N | 0.503032423 | None | None | N |
| R/Q | 0.1375 | likely_benign | 0.1253 | benign | -0.223 | Destabilizing | 1.0 | D | 0.712 | prob.delet. | None | None | None | None | N |
| R/S | 0.5818 | likely_pathogenic | 0.5248 | ambiguous | -0.766 | Destabilizing | 1.0 | D | 0.694 | prob.neutral | D | 0.576121595 | None | None | N |
| R/T | 0.3457 | ambiguous | 0.3032 | benign | -0.406 | Destabilizing | 1.0 | D | 0.688 | prob.neutral | None | None | None | None | N |
| R/V | 0.3611 | ambiguous | 0.3283 | benign | 0.154 | Stabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| R/W | 0.194 | likely_benign | 0.1837 | benign | 0.089 | Stabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | N |
| R/Y | 0.4111 | ambiguous | 0.3697 | ambiguous | 0.368 | Stabilizing | 1.0 | D | 0.709 | 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.