Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25084 | 75475;75476;75477 | chr2:178570882;178570881;178570880 | chr2:179435609;179435608;179435607 |
| N2AB | 23443 | 70552;70553;70554 | chr2:178570882;178570881;178570880 | chr2:179435609;179435608;179435607 |
| N2A | 22516 | 67771;67772;67773 | chr2:178570882;178570881;178570880 | chr2:179435609;179435608;179435607 |
| N2B | 16019 | 48280;48281;48282 | chr2:178570882;178570881;178570880 | chr2:179435609;179435608;179435607 |
| Novex-1 | 16144 | 48655;48656;48657 | chr2:178570882;178570881;178570880 | chr2:179435609;179435608;179435607 |
| Novex-2 | 16211 | 48856;48857;48858 | chr2:178570882;178570881;178570880 | chr2:179435609;179435608;179435607 |
| 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/G | None | None | 0.855 | D | 0.609 | 0.318 | 0.521970134296 | gnomAD-4.0.0 | 6.84311E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99588E-07 | 0 | 0 |
| R/Q | rs794729496  |
-1.023 | 0.989 | N | 0.624 | 0.276 | 0.149567049428 | gnomAD-2.1.1 | 3.93E-05 | None | None | None | None | I | None | 4.13E-05 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 2.39789E-04 | 2.35E-05 | 0 |
| R/Q | rs794729496 |
-1.023 | 0.989 | N | 0.624 | 0.276 | 0.149567049428 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/Q | rs794729496 |
-1.023 | 0.989 | N | 0.624 | 0.276 | 0.149567049428 | gnomAD-4.0.0 | 1.79743E-05 | None | None | None | None | I | None | 1.33547E-05 | 0 | None | 0 | 2.23075E-05 | None | 1.40594E-04 | 0 | 1.2716E-05 | 2.19597E-05 | 1.60143E-05 |
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 | 0.8348 | likely_pathogenic | 0.8486 | pathogenic | -1.675 | Destabilizing | 0.019 | N | 0.317 | neutral | None | None | None | None | I |
| R/C | 0.294 | likely_benign | 0.3211 | benign | -1.788 | Destabilizing | 0.994 | D | 0.704 | prob.neutral | None | None | None | None | I |
| R/D | 0.9818 | likely_pathogenic | 0.9831 | pathogenic | -0.807 | Destabilizing | 0.978 | D | 0.655 | neutral | None | None | None | None | I |
| R/E | 0.756 | likely_pathogenic | 0.7823 | pathogenic | -0.689 | Destabilizing | 0.86 | D | 0.581 | neutral | None | None | None | None | I |
| R/F | 0.8517 | likely_pathogenic | 0.8772 | pathogenic | -1.73 | Destabilizing | 0.978 | D | 0.711 | prob.delet. | None | None | None | None | I |
| R/G | 0.7659 | likely_pathogenic | 0.7915 | pathogenic | -1.949 | Destabilizing | 0.855 | D | 0.609 | neutral | D | 0.522503329 | None | None | I |
| R/H | 0.2269 | likely_benign | 0.2467 | benign | -2.011 | Highly Destabilizing | 0.993 | D | 0.602 | neutral | None | None | None | None | I |
| R/I | 0.5976 | likely_pathogenic | 0.6284 | pathogenic | -0.924 | Destabilizing | 0.956 | D | 0.712 | prob.delet. | None | None | None | None | I |
| R/K | 0.0933 | likely_benign | 0.1009 | benign | -1.614 | Destabilizing | 0.076 | N | 0.231 | neutral | None | None | None | None | I |
| R/L | 0.5798 | likely_pathogenic | 0.6033 | pathogenic | -0.924 | Destabilizing | 0.855 | D | 0.607 | neutral | N | 0.483808868 | None | None | I |
| R/M | 0.575 | likely_pathogenic | 0.6093 | pathogenic | -1.019 | Destabilizing | 0.998 | D | 0.653 | neutral | None | None | None | None | I |
| R/N | 0.9324 | likely_pathogenic | 0.9421 | pathogenic | -1.11 | Destabilizing | 0.978 | D | 0.611 | neutral | None | None | None | None | I |
| R/P | 0.9902 | likely_pathogenic | 0.9898 | pathogenic | -1.159 | Destabilizing | 0.988 | D | 0.709 | prob.delet. | N | 0.494957223 | None | None | I |
| R/Q | 0.1786 | likely_benign | 0.1917 | benign | -1.389 | Destabilizing | 0.989 | D | 0.624 | neutral | N | 0.481694069 | None | None | I |
| R/S | 0.8963 | likely_pathogenic | 0.908 | pathogenic | -2.048 | Highly Destabilizing | 0.754 | D | 0.611 | neutral | None | None | None | None | I |
| R/T | 0.6891 | likely_pathogenic | 0.7167 | pathogenic | -1.753 | Destabilizing | 0.86 | D | 0.627 | neutral | None | None | None | None | I |
| R/V | 0.6444 | likely_pathogenic | 0.6801 | pathogenic | -1.159 | Destabilizing | 0.915 | D | 0.669 | neutral | None | None | None | None | I |
| R/W | 0.3953 | ambiguous | 0.4344 | ambiguous | -1.281 | Destabilizing | 0.998 | D | 0.689 | prob.neutral | None | None | None | None | I |
| R/Y | 0.7154 | likely_pathogenic | 0.7478 | pathogenic | -0.994 | Destabilizing | 0.993 | D | 0.7 | 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.