Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26839 | 80740;80741;80742 | chr2:178565617;178565616;178565615 | chr2:179430344;179430343;179430342 |
| N2AB | 25198 | 75817;75818;75819 | chr2:178565617;178565616;178565615 | chr2:179430344;179430343;179430342 |
| N2A | 24271 | 73036;73037;73038 | chr2:178565617;178565616;178565615 | chr2:179430344;179430343;179430342 |
| N2B | 17774 | 53545;53546;53547 | chr2:178565617;178565616;178565615 | chr2:179430344;179430343;179430342 |
| Novex-1 | 17899 | 53920;53921;53922 | chr2:178565617;178565616;178565615 | chr2:179430344;179430343;179430342 |
| Novex-2 | 17966 | 54121;54122;54123 | chr2:178565617;178565616;178565615 | chr2:179430344;179430343;179430342 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/G | rs1157147648  |
-0.367 | 0.549 | D | 0.569 | 0.268 | 0.758059979048 | 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 |
| V/G | rs1157147648 |
-0.367 | 0.549 | D | 0.569 | 0.268 | 0.758059979048 | gnomAD-4.0.0 | 6.00161E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.56251E-06 | 0 | 0 |
| V/I | rs879175711 |
None | 0.016 | N | 0.207 | 0.09 | 0.547126614516 | gnomAD-4.0.0 | 2.05285E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.9957E-07 | 1.15937E-05 | 1.65706E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1451 | likely_benign | 0.1323 | benign | -0.442 | Destabilizing | 0.201 | N | 0.405 | neutral | N | 0.497143524 | None | None | I |
| V/C | 0.7112 | likely_pathogenic | 0.6909 | pathogenic | -0.582 | Destabilizing | 0.992 | D | 0.535 | neutral | None | None | None | None | I |
| V/D | 0.3346 | likely_benign | 0.3201 | benign | -0.233 | Destabilizing | 0.379 | N | 0.567 | neutral | N | 0.499663755 | None | None | I |
| V/E | 0.2246 | likely_benign | 0.2225 | benign | -0.358 | Destabilizing | 0.005 | N | 0.425 | neutral | None | None | None | None | I |
| V/F | 0.173 | likely_benign | 0.1582 | benign | -0.746 | Destabilizing | 0.896 | D | 0.572 | neutral | N | 0.502224057 | None | None | I |
| V/G | 0.2615 | likely_benign | 0.2455 | benign | -0.561 | Destabilizing | 0.549 | D | 0.569 | neutral | D | 0.523868766 | None | None | I |
| V/H | 0.4515 | ambiguous | 0.4243 | ambiguous | -0.191 | Destabilizing | 0.977 | D | 0.586 | neutral | None | None | None | None | I |
| V/I | 0.0744 | likely_benign | 0.0704 | benign | -0.283 | Destabilizing | 0.016 | N | 0.207 | neutral | N | 0.504069497 | None | None | I |
| V/K | 0.2474 | likely_benign | 0.2418 | benign | -0.346 | Destabilizing | 0.447 | N | 0.573 | neutral | None | None | None | None | I |
| V/L | 0.1541 | likely_benign | 0.1466 | benign | -0.283 | Destabilizing | 0.201 | N | 0.38 | neutral | N | 0.454411467 | None | None | I |
| V/M | 0.1073 | likely_benign | 0.0997 | benign | -0.257 | Destabilizing | 0.92 | D | 0.483 | neutral | None | None | None | None | I |
| V/N | 0.2167 | likely_benign | 0.2001 | benign | -0.074 | Destabilizing | 0.85 | D | 0.607 | neutral | None | None | None | None | I |
| V/P | 0.6862 | likely_pathogenic | 0.6657 | pathogenic | -0.301 | Destabilizing | 0.92 | D | 0.631 | neutral | None | None | None | None | I |
| V/Q | 0.2425 | likely_benign | 0.2343 | benign | -0.343 | Destabilizing | 0.739 | D | 0.622 | neutral | None | None | None | None | I |
| V/R | 0.2486 | likely_benign | 0.2352 | benign | 0.163 | Stabilizing | 0.85 | D | 0.608 | neutral | None | None | None | None | I |
| V/S | 0.165 | likely_benign | 0.1557 | benign | -0.437 | Destabilizing | 0.447 | N | 0.521 | neutral | None | None | None | None | I |
| V/T | 0.1067 | likely_benign | 0.0983 | benign | -0.462 | Destabilizing | 0.002 | N | 0.169 | neutral | None | None | None | None | I |
| V/W | 0.7907 | likely_pathogenic | 0.7709 | pathogenic | -0.815 | Destabilizing | 0.992 | D | 0.614 | neutral | None | None | None | None | I |
| V/Y | 0.5073 | ambiguous | 0.4878 | ambiguous | -0.5 | Destabilizing | 0.972 | D | 0.563 | 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.