Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35420 | 106483;106484;106485 | chr2:178530357;178530356;178530355 | chr2:179395084;179395083;179395082 |
| N2AB | 33779 | 101560;101561;101562 | chr2:178530357;178530356;178530355 | chr2:179395084;179395083;179395082 |
| N2A | 32852 | 98779;98780;98781 | chr2:178530357;178530356;178530355 | chr2:179395084;179395083;179395082 |
| N2B | 26355 | 79288;79289;79290 | chr2:178530357;178530356;178530355 | chr2:179395084;179395083;179395082 |
| Novex-1 | 26480 | 79663;79664;79665 | chr2:178530357;178530356;178530355 | chr2:179395084;179395083;179395082 |
| Novex-2 | 26547 | 79864;79865;79866 | chr2:178530357;178530356;178530355 | chr2:179395084;179395083;179395082 |
| 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/R | rs367732354  |
-0.896 | 0.44 | D | 0.726 | 0.735 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/R | rs367732354 |
-0.896 | 0.44 | D | 0.726 | 0.735 | None | gnomAD-4.0.0 | 6.57402E-06 | None | None | None | None | N | None | 2.41488E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | rs567191587 |
-2.182 | 0.611 | D | 0.651 | 0.651 | 0.518147779662 | gnomAD-2.1.1 | 3.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 4.60782E-04 | None | 0 | None | 0 | 0 | 0 |
| P/S | rs567191587 |
-2.182 | 0.611 | D | 0.651 | 0.651 | 0.518147779662 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 5.78258E-04 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | rs567191587 |
-2.182 | 0.611 | D | 0.651 | 0.651 | 0.518147779662 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| P/S | rs567191587 |
-2.182 | 0.611 | D | 0.651 | 0.651 | 0.518147779662 | gnomAD-4.0.0 | 4.95683E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.78301E-04 | None | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.3315 | likely_benign | 0.3404 | ambiguous | -1.586 | Destabilizing | 0.393 | N | 0.643 | neutral | D | 0.577777003 | None | None | N |
| P/C | 0.9474 | likely_pathogenic | 0.9561 | pathogenic | -1.345 | Destabilizing | 0.994 | D | 0.795 | deleterious | None | None | None | None | N |
| P/D | 0.982 | likely_pathogenic | 0.9794 | pathogenic | -1.552 | Destabilizing | 0.301 | N | 0.646 | neutral | None | None | None | None | N |
| P/E | 0.943 | likely_pathogenic | 0.9348 | pathogenic | -1.562 | Destabilizing | 0.012 | N | 0.495 | neutral | None | None | None | None | N |
| P/F | 0.9773 | likely_pathogenic | 0.9813 | pathogenic | -1.404 | Destabilizing | 0.978 | D | 0.807 | deleterious | None | None | None | None | N |
| P/G | 0.9022 | likely_pathogenic | 0.8985 | pathogenic | -1.88 | Destabilizing | 0.675 | D | 0.709 | prob.delet. | None | None | None | None | N |
| P/H | 0.9559 | likely_pathogenic | 0.9545 | pathogenic | -1.361 | Destabilizing | 0.937 | D | 0.783 | deleterious | None | None | None | None | N |
| P/I | 0.7537 | likely_pathogenic | 0.8057 | pathogenic | -0.878 | Destabilizing | 0.937 | D | 0.803 | deleterious | None | None | None | None | N |
| P/K | 0.9759 | likely_pathogenic | 0.9735 | pathogenic | -1.175 | Destabilizing | 0.301 | N | 0.645 | neutral | None | None | None | None | N |
| P/L | 0.5281 | ambiguous | 0.5704 | pathogenic | -0.878 | Destabilizing | 0.611 | D | 0.762 | deleterious | D | 0.601629242 | None | None | N |
| P/M | 0.8634 | likely_pathogenic | 0.8843 | pathogenic | -0.783 | Destabilizing | 0.978 | D | 0.777 | deleterious | None | None | None | None | N |
| P/N | 0.9641 | likely_pathogenic | 0.9571 | pathogenic | -1.029 | Destabilizing | 0.675 | D | 0.74 | deleterious | None | None | None | None | N |
| P/Q | 0.9193 | likely_pathogenic | 0.9129 | pathogenic | -1.262 | Destabilizing | 0.021 | N | 0.552 | neutral | D | 0.634101932 | None | None | N |
| P/R | 0.9433 | likely_pathogenic | 0.9385 | pathogenic | -0.661 | Destabilizing | 0.44 | N | 0.726 | prob.delet. | D | 0.634101933 | None | None | N |
| P/S | 0.8034 | likely_pathogenic | 0.7935 | pathogenic | -1.568 | Destabilizing | 0.611 | D | 0.651 | neutral | D | 0.617446798 | None | None | N |
| P/T | 0.6004 | likely_pathogenic | 0.6085 | pathogenic | -1.47 | Destabilizing | 0.611 | D | 0.671 | neutral | D | 0.633900128 | None | None | N |
| P/V | 0.6222 | likely_pathogenic | 0.6782 | pathogenic | -1.081 | Destabilizing | 0.808 | D | 0.735 | prob.delet. | None | None | None | None | N |
| P/W | 0.9914 | likely_pathogenic | 0.9935 | pathogenic | -1.521 | Destabilizing | 0.994 | D | 0.794 | deleterious | None | None | None | None | N |
| P/Y | 0.9777 | likely_pathogenic | 0.9806 | pathogenic | -1.219 | Destabilizing | 0.978 | D | 0.807 | 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.