Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24336 | 73231;73232;73233 | chr2:178573126;178573125;178573124 | chr2:179437853;179437852;179437851 |
| N2AB | 22695 | 68308;68309;68310 | chr2:178573126;178573125;178573124 | chr2:179437853;179437852;179437851 |
| N2A | 21768 | 65527;65528;65529 | chr2:178573126;178573125;178573124 | chr2:179437853;179437852;179437851 |
| N2B | 15271 | 46036;46037;46038 | chr2:178573126;178573125;178573124 | chr2:179437853;179437852;179437851 |
| Novex-1 | 15396 | 46411;46412;46413 | chr2:178573126;178573125;178573124 | chr2:179437853;179437852;179437851 |
| Novex-2 | 15463 | 46612;46613;46614 | chr2:178573126;178573125;178573124 | chr2:179437853;179437852;179437851 |
| 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/G | rs1708845261  |
None | 0.896 | N | 0.412 | 0.162 | 0.239305524855 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/G | rs1708845261 |
None | 0.896 | N | 0.412 | 0.162 | 0.239305524855 | gnomAD-4.0.0 | 6.57601E-06 | None | None | None | None | N | None | 0 | 6.55308E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/N | None | None | 0.896 | N | 0.449 | 0.2 | 0.232513804876 | gnomAD-4.0.0 | 1.59227E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.78164E-05 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1959 | likely_benign | 0.2028 | benign | -0.53 | Destabilizing | 0.702 | D | 0.384 | neutral | None | None | None | None | N |
| S/C | 0.2142 | likely_benign | 0.2182 | benign | -0.479 | Destabilizing | 0.999 | D | 0.493 | neutral | N | 0.515178299 | None | None | N |
| S/D | 0.7623 | likely_pathogenic | 0.6997 | pathogenic | -1.039 | Destabilizing | 0.919 | D | 0.429 | neutral | None | None | None | None | N |
| S/E | 0.9232 | likely_pathogenic | 0.9023 | pathogenic | -1.1 | Destabilizing | 0.919 | D | 0.418 | neutral | None | None | None | None | N |
| S/F | 0.7135 | likely_pathogenic | 0.6905 | pathogenic | -1.195 | Destabilizing | 0.988 | D | 0.559 | neutral | None | None | None | None | N |
| S/G | 0.1227 | likely_benign | 0.1174 | benign | -0.66 | Destabilizing | 0.896 | D | 0.412 | neutral | N | 0.494276578 | None | None | N |
| S/H | 0.7703 | likely_pathogenic | 0.737 | pathogenic | -1.287 | Destabilizing | 0.999 | D | 0.493 | neutral | None | None | None | None | N |
| S/I | 0.7563 | likely_pathogenic | 0.7401 | pathogenic | -0.303 | Destabilizing | 0.968 | D | 0.48 | neutral | N | 0.492301104 | None | None | N |
| S/K | 0.9576 | likely_pathogenic | 0.9511 | pathogenic | -0.629 | Destabilizing | 0.919 | D | 0.425 | neutral | None | None | None | None | N |
| S/L | 0.3203 | likely_benign | 0.3168 | benign | -0.303 | Destabilizing | 0.851 | D | 0.446 | neutral | None | None | None | None | N |
| S/M | 0.4893 | ambiguous | 0.4903 | ambiguous | 0.257 | Stabilizing | 0.999 | D | 0.496 | neutral | None | None | None | None | N |
| S/N | 0.3778 | ambiguous | 0.3414 | ambiguous | -0.639 | Destabilizing | 0.896 | D | 0.449 | neutral | N | 0.51428649 | None | None | N |
| S/P | 0.9682 | likely_pathogenic | 0.9554 | pathogenic | -0.352 | Destabilizing | 0.988 | D | 0.465 | neutral | None | None | None | None | N |
| S/Q | 0.8793 | likely_pathogenic | 0.868 | pathogenic | -1.03 | Destabilizing | 0.988 | D | 0.458 | neutral | None | None | None | None | N |
| S/R | 0.9402 | likely_pathogenic | 0.9329 | pathogenic | -0.318 | Destabilizing | 0.984 | D | 0.464 | neutral | N | 0.492604496 | None | None | N |
| S/T | 0.0787 | likely_benign | 0.0808 | benign | -0.594 | Destabilizing | 0.016 | N | 0.093 | neutral | N | 0.389301196 | None | None | N |
| S/V | 0.6395 | likely_pathogenic | 0.6227 | pathogenic | -0.352 | Destabilizing | 0.851 | D | 0.452 | neutral | None | None | None | None | N |
| S/W | 0.8425 | likely_pathogenic | 0.8243 | pathogenic | -1.194 | Destabilizing | 0.999 | D | 0.597 | neutral | None | None | None | None | N |
| S/Y | 0.6438 | likely_pathogenic | 0.6208 | pathogenic | -0.876 | Destabilizing | 0.996 | D | 0.559 | 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.