Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3862 | 11809;11810;11811 | chr2:178741649;178741648;178741647 | chr2:179606376;179606375;179606374 |
| N2AB | 3545 | 10858;10859;10860 | chr2:178741649;178741648;178741647 | chr2:179606376;179606375;179606374 |
| N2A | None | None | chr2:None | chr2:None |
| N2B | 3499 | 10720;10721;10722 | chr2:178741649;178741648;178741647 | chr2:179606376;179606375;179606374 |
| Novex-1 | 3624 | 11095;11096;11097 | chr2:178741649;178741648;178741647 | chr2:179606376;179606375;179606374 |
| Novex-2 | 3691 | 11296;11297;11298 | chr2:178741649;178741648;178741647 | chr2:179606376;179606375;179606374 |
| 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 | rs201652675  |
0.251 | 0.627 | N | 0.373 | 0.196 | 0.33835085245 | gnomAD-2.1.1 | 4.83E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.06697E-04 | 0 |
| P/R | rs201652675 |
0.251 | 0.627 | N | 0.373 | 0.196 | 0.33835085245 | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.17609E-04 | 0 | 0 |
| P/R | rs201652675 |
0.251 | 0.627 | N | 0.373 | 0.196 | 0.33835085245 | gnomAD-4.0.0 | 7.12636E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.74743E-05 | 0 | 0 |
| P/S | rs375406698 |
None | None | N | 0.108 | 0.073 | None | gnomAD-4.0.0 | 1.36839E-06 | None | None | None | None | I | None | 0 | 2.23624E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15931E-05 | 0 |
| P/T | rs375406698 |
-0.251 | 0.001 | N | 0.11 | 0.064 | 0.242825505644 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.67E-05 | 0 |
| P/T | rs375406698 |
-0.251 | 0.001 | N | 0.11 | 0.064 | 0.242825505644 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| P/T | rs375406698 |
-0.251 | 0.001 | N | 0.11 | 0.064 | 0.242825505644 | gnomAD-4.0.0 | 1.79712E-05 | None | None | None | None | I | None | 0 | 3.33467E-05 | None | 0 | 0 | None | 0 | 0 | 2.28855E-05 | 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 | 0.1016 | likely_benign | 0.098 | benign | -0.46 | Destabilizing | 0.09 | N | 0.275 | neutral | N | 0.482006266 | None | None | I |
| P/C | 0.6814 | likely_pathogenic | 0.6031 | pathogenic | -0.729 | Destabilizing | 0.944 | D | 0.348 | neutral | None | None | None | None | I |
| P/D | 0.5709 | likely_pathogenic | 0.5397 | ambiguous | -0.015 | Destabilizing | 0.241 | N | 0.307 | neutral | None | None | None | None | I |
| P/E | 0.3663 | ambiguous | 0.3516 | ambiguous | -0.084 | Destabilizing | 0.388 | N | 0.313 | neutral | None | None | None | None | I |
| P/F | 0.6972 | likely_pathogenic | 0.6111 | pathogenic | -0.522 | Destabilizing | 0.818 | D | 0.364 | neutral | None | None | None | None | I |
| P/G | 0.49 | ambiguous | 0.4422 | ambiguous | -0.615 | Destabilizing | 0.116 | N | 0.298 | neutral | None | None | None | None | I |
| P/H | 0.2974 | likely_benign | 0.2442 | benign | -0.06 | Destabilizing | 0.773 | D | 0.337 | neutral | N | 0.508801056 | None | None | I |
| P/I | 0.5259 | ambiguous | 0.4537 | ambiguous | -0.184 | Destabilizing | 0.527 | D | 0.387 | neutral | None | None | None | None | I |
| P/K | 0.4579 | ambiguous | 0.3923 | ambiguous | -0.392 | Destabilizing | 0.241 | N | 0.305 | neutral | None | None | None | None | I |
| P/L | 0.1911 | likely_benign | 0.1648 | benign | -0.184 | Destabilizing | 0.193 | N | 0.387 | neutral | N | 0.49645134 | None | None | I |
| P/M | 0.5229 | ambiguous | 0.4622 | ambiguous | -0.486 | Destabilizing | 0.818 | D | 0.331 | neutral | None | None | None | None | I |
| P/N | 0.4589 | ambiguous | 0.4124 | ambiguous | -0.251 | Destabilizing | 0.002 | N | 0.195 | neutral | None | None | None | None | I |
| P/Q | 0.2309 | likely_benign | 0.2058 | benign | -0.384 | Destabilizing | 0.69 | D | 0.366 | neutral | None | None | None | None | I |
| P/R | 0.2641 | likely_benign | 0.2267 | benign | 0.017 | Stabilizing | 0.627 | D | 0.373 | neutral | N | 0.487029605 | None | None | I |
| P/S | 0.155 | likely_benign | 0.1361 | benign | -0.665 | Destabilizing | None | N | 0.108 | neutral | N | 0.426534581 | None | None | I |
| P/T | 0.1577 | likely_benign | 0.1301 | benign | -0.622 | Destabilizing | 0.001 | N | 0.11 | neutral | N | 0.484932479 | None | None | I |
| P/V | 0.3689 | ambiguous | 0.3254 | benign | -0.243 | Destabilizing | 0.241 | N | 0.356 | neutral | None | None | None | None | I |
| P/W | 0.8254 | likely_pathogenic | 0.7568 | pathogenic | -0.619 | Destabilizing | 0.981 | D | 0.413 | neutral | None | None | None | None | I |
| P/Y | 0.6089 | likely_pathogenic | 0.5202 | ambiguous | -0.326 | Destabilizing | 0.818 | D | 0.365 | 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.