Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29578 | 88957;88958;88959 | chr2:178554615;178554614;178554613 | chr2:179419342;179419341;179419340 |
| N2AB | 27937 | 84034;84035;84036 | chr2:178554615;178554614;178554613 | chr2:179419342;179419341;179419340 |
| N2A | 27010 | 81253;81254;81255 | chr2:178554615;178554614;178554613 | chr2:179419342;179419341;179419340 |
| N2B | 20513 | 61762;61763;61764 | chr2:178554615;178554614;178554613 | chr2:179419342;179419341;179419340 |
| Novex-1 | 20638 | 62137;62138;62139 | chr2:178554615;178554614;178554613 | chr2:179419342;179419341;179419340 |
| Novex-2 | 20705 | 62338;62339;62340 | chr2:178554615;178554614;178554613 | chr2:179419342;179419341;179419340 |
| 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 | rs539906386  |
-0.471 | 1.0 | N | 0.731 | 0.368 | 0.685689443777 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| R/C | rs539906386 |
-0.471 | 1.0 | N | 0.731 | 0.368 | 0.685689443777 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/C | rs539906386 |
-0.471 | 1.0 | N | 0.731 | 0.368 | 0.685689443777 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| R/C | rs539906386 |
-0.471 | 1.0 | N | 0.731 | 0.368 | 0.685689443777 | gnomAD-4.0.0 | 3.09824E-06 | None | None | None | None | I | None | 0 | 1.66639E-05 | None | 0 | 4.45911E-05 | None | 0 | 0 | 1.69515E-06 | 0 | 0 |
| R/H | rs374147064 |
-1.271 | 1.0 | N | 0.679 | 0.371 | None | gnomAD-2.1.1 | 1.3924E-04 | None | None | None | None | I | None | 1.07465E-03 | 1.13109E-04 | None | 0 | 3.58938E-04 | None | 3.27E-05 | None | 0 | 0 | 1.40371E-04 |
| R/H | rs374147064 |
-1.271 | 1.0 | N | 0.679 | 0.371 | None | gnomAD-3.1.2 | 3.08946E-04 | None | None | None | None | I | None | 8.69103E-04 | 0 | 0 | 0 | 1.93125E-03 | None | 0 | 0 | 0 | 0 | 4.77555E-04 |
| R/H | rs374147064 |
-1.271 | 1.0 | N | 0.679 | 0.371 | None | 1000 genomes | 1.39776E-03 | None | None | None | None | I | None | 1.5E-03 | 0 | None | None | 5E-03 | 0 | None | None | None | 0 | None |
| R/H | rs374147064 |
-1.271 | 1.0 | N | 0.679 | 0.371 | None | gnomAD-4.0.0 | 6.75395E-05 | None | None | None | None | I | None | 9.06401E-04 | 8.33139E-05 | None | 0 | 3.78991E-04 | None | 1.56221E-05 | 0 | 4.23789E-06 | 1.09794E-05 | 1.92049E-04 |
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 | 0.9826 | likely_pathogenic | 0.9762 | pathogenic | -0.365 | Destabilizing | 0.999 | D | 0.445 | neutral | None | None | None | None | I |
| R/C | 0.881 | likely_pathogenic | 0.8105 | pathogenic | -0.5 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | N | 0.509983605 | None | None | I |
| R/D | 0.995 | likely_pathogenic | 0.9927 | pathogenic | -0.046 | Destabilizing | 1.0 | D | 0.65 | neutral | None | None | None | None | I |
| R/E | 0.9724 | likely_pathogenic | 0.9595 | pathogenic | 0.035 | Stabilizing | 0.999 | D | 0.495 | neutral | None | None | None | None | I |
| R/F | 0.9899 | likely_pathogenic | 0.9855 | pathogenic | -0.489 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | I |
| R/G | 0.9699 | likely_pathogenic | 0.9571 | pathogenic | -0.594 | Destabilizing | 1.0 | D | 0.553 | neutral | N | 0.496524662 | None | None | I |
| R/H | 0.6021 | likely_pathogenic | 0.3865 | ambiguous | -0.961 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | N | 0.472254157 | None | None | I |
| R/I | 0.9824 | likely_pathogenic | 0.9734 | pathogenic | 0.218 | Stabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | I |
| R/K | 0.6702 | likely_pathogenic | 0.5897 | pathogenic | -0.441 | Destabilizing | 0.998 | D | 0.395 | neutral | None | None | None | None | I |
| R/L | 0.941 | likely_pathogenic | 0.9182 | pathogenic | 0.218 | Stabilizing | 1.0 | D | 0.553 | neutral | N | 0.482218111 | None | None | I |
| R/M | 0.9766 | likely_pathogenic | 0.9628 | pathogenic | -0.155 | Destabilizing | 1.0 | D | 0.676 | prob.neutral | None | None | None | None | I |
| R/N | 0.9893 | likely_pathogenic | 0.9848 | pathogenic | -0.113 | Destabilizing | 1.0 | D | 0.647 | neutral | None | None | None | None | I |
| R/P | 0.9949 | likely_pathogenic | 0.9937 | pathogenic | 0.045 | Stabilizing | 1.0 | D | 0.653 | neutral | N | 0.465772924 | None | None | I |
| R/Q | 0.7554 | likely_pathogenic | 0.656 | pathogenic | -0.259 | Destabilizing | 1.0 | D | 0.641 | neutral | None | None | None | None | I |
| R/S | 0.9857 | likely_pathogenic | 0.9806 | pathogenic | -0.657 | Destabilizing | 1.0 | D | 0.611 | neutral | N | 0.469223417 | None | None | I |
| R/T | 0.9819 | likely_pathogenic | 0.9709 | pathogenic | -0.424 | Destabilizing | 1.0 | D | 0.615 | neutral | None | None | None | None | I |
| R/V | 0.9816 | likely_pathogenic | 0.974 | pathogenic | 0.045 | Stabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | I |
| R/W | 0.8623 | likely_pathogenic | 0.8072 | pathogenic | -0.382 | Destabilizing | 1.0 | D | 0.746 | deleterious | None | None | None | None | I |
| R/Y | 0.9684 | likely_pathogenic | 0.9534 | pathogenic | -0.017 | Destabilizing | 1.0 | D | 0.688 | prob.neutral | None | None | None | None | I |
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.