Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17892 | 53899;53900;53901 | chr2:178605621;178605620;178605619 | chr2:179470348;179470347;179470346 |
| N2AB | 16251 | 48976;48977;48978 | chr2:178605621;178605620;178605619 | chr2:179470348;179470347;179470346 |
| N2A | 15324 | 46195;46196;46197 | chr2:178605621;178605620;178605619 | chr2:179470348;179470347;179470346 |
| N2B | 8827 | 26704;26705;26706 | chr2:178605621;178605620;178605619 | chr2:179470348;179470347;179470346 |
| Novex-1 | 8952 | 27079;27080;27081 | chr2:178605621;178605620;178605619 | chr2:179470348;179470347;179470346 |
| Novex-2 | 9019 | 27280;27281;27282 | chr2:178605621;178605620;178605619 | chr2:179470348;179470347;179470346 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/C | None | None | 0.002 | N | 0.539 | 0.165 | 0.24896430686 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 6.07533E-05 | 0 |
| S/N | None | None | 0.22 | N | 0.695 | 0.281 | 0.239305524855 | gnomAD-4.0.0 | 1.59493E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43571E-05 | 0 |
| S/R | rs2154195662  |
None | 0.002 | N | 0.5 | 0.28 | 0.173771789658 | gnomAD-4.0.0 | 3.60097E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.62501E-06 | 6.07533E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1343 | likely_benign | 0.1347 | benign | -0.607 | Destabilizing | 0.072 | N | 0.595 | neutral | None | None | None | None | I |
| S/C | 0.0601 | likely_benign | 0.0783 | benign | -0.478 | Destabilizing | 0.002 | N | 0.539 | neutral | N | 0.475500296 | None | None | I |
| S/D | 0.815 | likely_pathogenic | 0.8069 | pathogenic | -0.541 | Destabilizing | 0.272 | N | 0.677 | prob.neutral | None | None | None | None | I |
| S/E | 0.8465 | likely_pathogenic | 0.841 | pathogenic | -0.579 | Destabilizing | 0.157 | N | 0.674 | neutral | None | None | None | None | I |
| S/F | 0.3476 | ambiguous | 0.3002 | benign | -0.953 | Destabilizing | 0.726 | D | 0.705 | prob.neutral | None | None | None | None | I |
| S/G | 0.3019 | likely_benign | 0.2754 | benign | -0.807 | Destabilizing | 0.22 | N | 0.607 | neutral | N | 0.519630808 | None | None | I |
| S/H | 0.3896 | ambiguous | 0.376 | ambiguous | -1.359 | Destabilizing | 0.909 | D | 0.646 | neutral | None | None | None | None | I |
| S/I | 0.4027 | ambiguous | 0.3675 | ambiguous | -0.192 | Destabilizing | 0.497 | N | 0.704 | prob.neutral | N | 0.489703757 | None | None | I |
| S/K | 0.8305 | likely_pathogenic | 0.8132 | pathogenic | -0.74 | Destabilizing | 0.157 | N | 0.634 | neutral | None | None | None | None | I |
| S/L | 0.1789 | likely_benign | 0.157 | benign | -0.192 | Destabilizing | 0.157 | N | 0.656 | neutral | None | None | None | None | I |
| S/M | 0.3269 | likely_benign | 0.2879 | benign | 0.216 | Stabilizing | 0.968 | D | 0.646 | neutral | None | None | None | None | I |
| S/N | 0.3832 | ambiguous | 0.3461 | ambiguous | -0.653 | Destabilizing | 0.22 | N | 0.695 | prob.neutral | N | 0.49381836 | None | None | I |
| S/P | 0.9863 | likely_pathogenic | 0.9775 | pathogenic | -0.298 | Destabilizing | 0.726 | D | 0.666 | neutral | None | None | None | None | I |
| S/Q | 0.6399 | likely_pathogenic | 0.637 | pathogenic | -0.923 | Destabilizing | 0.567 | D | 0.68 | prob.neutral | None | None | None | None | I |
| S/R | 0.7774 | likely_pathogenic | 0.7593 | pathogenic | -0.528 | Destabilizing | 0.002 | N | 0.5 | neutral | N | 0.497221721 | None | None | I |
| S/T | 0.2147 | likely_benign | 0.1936 | benign | -0.663 | Destabilizing | 0.22 | N | 0.634 | neutral | N | 0.515134639 | None | None | I |
| S/V | 0.3686 | ambiguous | 0.3325 | benign | -0.298 | Destabilizing | 0.396 | N | 0.685 | prob.neutral | None | None | None | None | I |
| S/W | 0.5498 | ambiguous | 0.5205 | ambiguous | -0.919 | Destabilizing | 0.968 | D | 0.727 | prob.delet. | None | None | None | None | I |
| S/Y | 0.2848 | likely_benign | 0.2649 | benign | -0.653 | Destabilizing | 0.726 | D | 0.705 | 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.