Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20699 | 62320;62321;62322 | chr2:178589630;178589629;178589628 | chr2:179454357;179454356;179454355 |
| N2AB | 19058 | 57397;57398;57399 | chr2:178589630;178589629;178589628 | chr2:179454357;179454356;179454355 |
| N2A | 18131 | 54616;54617;54618 | chr2:178589630;178589629;178589628 | chr2:179454357;179454356;179454355 |
| N2B | 11634 | 35125;35126;35127 | chr2:178589630;178589629;178589628 | chr2:179454357;179454356;179454355 |
| Novex-1 | 11759 | 35500;35501;35502 | chr2:178589630;178589629;178589628 | chr2:179454357;179454356;179454355 |
| Novex-2 | 11826 | 35701;35702;35703 | chr2:178589630;178589629;178589628 | chr2:179454357;179454356;179454355 |
| 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/L | rs1553641061  |
None | 0.999 | N | 0.67 | 0.442 | 0.675737440431 | gnomAD-4.0.0 | 3.18458E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.86681E-05 | 0 |
| P/Q | None | None | 1.0 | N | 0.641 | 0.441 | 0.434045841721 | gnomAD-4.0.0 | 1.59229E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.4334E-05 | 0 |
| P/S | rs760330778 |
-0.027 | 0.998 | N | 0.619 | 0.456 | 0.392547445146 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 8.94E-06 | 0 |
| P/S | rs760330778 |
-0.027 | 0.998 | N | 0.619 | 0.456 | 0.392547445146 | gnomAD-4.0.0 | 3.18446E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86015E-06 | 1.43336E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.1992 | likely_benign | 0.1373 | benign | -0.513 | Destabilizing | 0.767 | D | 0.426 | neutral | N | 0.468890477 | None | None | N |
| P/C | 0.8718 | likely_pathogenic | 0.7784 | pathogenic | -0.504 | Destabilizing | 1.0 | D | 0.62 | neutral | None | None | None | None | N |
| P/D | 0.8152 | likely_pathogenic | 0.7095 | pathogenic | -0.401 | Destabilizing | 1.0 | D | 0.673 | neutral | None | None | None | None | N |
| P/E | 0.5821 | likely_pathogenic | 0.4346 | ambiguous | -0.532 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | N |
| P/F | 0.8991 | likely_pathogenic | 0.8192 | pathogenic | -0.885 | Destabilizing | 1.0 | D | 0.625 | neutral | None | None | None | None | N |
| P/G | 0.72 | likely_pathogenic | 0.6084 | pathogenic | -0.635 | Destabilizing | 0.997 | D | 0.608 | neutral | None | None | None | None | N |
| P/H | 0.5359 | ambiguous | 0.3966 | ambiguous | -0.268 | Destabilizing | 1.0 | D | 0.616 | neutral | None | None | None | None | N |
| P/I | 0.6643 | likely_pathogenic | 0.4931 | ambiguous | -0.348 | Destabilizing | 1.0 | D | 0.66 | neutral | None | None | None | None | N |
| P/K | 0.5631 | ambiguous | 0.4184 | ambiguous | -0.313 | Destabilizing | 1.0 | D | 0.682 | prob.neutral | None | None | None | None | N |
| P/L | 0.395 | ambiguous | 0.2633 | benign | -0.348 | Destabilizing | 0.999 | D | 0.67 | neutral | N | 0.516508199 | None | None | N |
| P/M | 0.6857 | likely_pathogenic | 0.5461 | ambiguous | -0.204 | Destabilizing | 1.0 | D | 0.612 | neutral | None | None | None | None | N |
| P/N | 0.7069 | likely_pathogenic | 0.5843 | pathogenic | -0.001 | Destabilizing | 1.0 | D | 0.665 | neutral | None | None | None | None | N |
| P/Q | 0.3536 | ambiguous | 0.2391 | benign | -0.314 | Destabilizing | 1.0 | D | 0.641 | neutral | N | 0.480753761 | None | None | N |
| P/R | 0.4032 | ambiguous | 0.284 | benign | 0.234 | Stabilizing | 0.999 | D | 0.663 | neutral | N | 0.50638187 | None | None | N |
| P/S | 0.4094 | ambiguous | 0.2928 | benign | -0.351 | Destabilizing | 0.998 | D | 0.619 | neutral | N | 0.480246782 | None | None | N |
| P/T | 0.3583 | ambiguous | 0.2325 | benign | -0.386 | Destabilizing | 0.999 | D | 0.617 | neutral | N | 0.485273212 | None | None | N |
| P/V | 0.48 | ambiguous | 0.3362 | benign | -0.368 | Destabilizing | 0.999 | D | 0.627 | neutral | None | None | None | None | N |
| P/W | 0.9428 | likely_pathogenic | 0.8935 | pathogenic | -0.938 | Destabilizing | 1.0 | D | 0.656 | neutral | None | None | None | None | N |
| P/Y | 0.8546 | likely_pathogenic | 0.7592 | pathogenic | -0.617 | Destabilizing | 1.0 | D | 0.626 | neutral | 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.