Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18570 | 55933;55934;55935 | chr2:178601289;178601288;178601287 | chr2:179466016;179466015;179466014 |
| N2AB | 16929 | 51010;51011;51012 | chr2:178601289;178601288;178601287 | chr2:179466016;179466015;179466014 |
| N2A | 16002 | 48229;48230;48231 | chr2:178601289;178601288;178601287 | chr2:179466016;179466015;179466014 |
| N2B | 9505 | 28738;28739;28740 | chr2:178601289;178601288;178601287 | chr2:179466016;179466015;179466014 |
| Novex-1 | 9630 | 29113;29114;29115 | chr2:178601289;178601288;178601287 | chr2:179466016;179466015;179466014 |
| Novex-2 | 9697 | 29314;29315;29316 | chr2:178601289;178601288;178601287 | chr2:179466016;179466015;179466014 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | None | None | 0.915 | N | 0.619 | 0.182 | 0.33340067248 | gnomAD-4.0.0 | 1.69102E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.00255E-06 | 0 | 0 |
| R/K | rs1427580402  |
-0.649 | 0.817 | N | 0.433 | 0.147 | None | gnomAD-2.1.1 | 9.12E-06 | None | None | None | None | N | None | 0 | 3.53E-05 | None | 0 | 0 | None | 0 | None | 0 | 9.72E-06 | 0 |
| R/K | rs1427580402 |
-0.649 | 0.817 | N | 0.433 | 0.147 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/K | rs1427580402 |
-0.649 | 0.817 | N | 0.433 | 0.147 | None | gnomAD-4.0.0 | 9.50676E-06 | None | None | None | None | N | None | 0 | 1.92753E-05 | None | 0 | 0 | None | 0 | 0 | 1.50739E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.5785 | likely_pathogenic | 0.4172 | ambiguous | -0.124 | Destabilizing | 0.745 | D | 0.505 | neutral | None | None | None | None | N |
| R/C | 0.3392 | likely_benign | 0.238 | benign | -0.382 | Destabilizing | 0.998 | D | 0.702 | prob.delet. | None | None | None | None | N |
| R/D | 0.8837 | likely_pathogenic | 0.7936 | pathogenic | 0.034 | Stabilizing | 0.935 | D | 0.671 | prob.neutral | None | None | None | None | N |
| R/E | 0.5698 | likely_pathogenic | 0.4242 | ambiguous | 0.118 | Stabilizing | 0.935 | D | 0.441 | neutral | None | None | None | None | N |
| R/F | 0.8389 | likely_pathogenic | 0.7148 | pathogenic | -0.353 | Destabilizing | 0.994 | D | 0.687 | prob.delet. | None | None | None | None | N |
| R/G | 0.482 | ambiguous | 0.3024 | benign | -0.325 | Destabilizing | 0.915 | D | 0.619 | neutral | N | 0.434166694 | None | None | N |
| R/H | 0.2292 | likely_benign | 0.1653 | benign | -0.87 | Destabilizing | 0.994 | D | 0.519 | neutral | None | None | None | None | N |
| R/I | 0.5607 | ambiguous | 0.434 | ambiguous | 0.372 | Stabilizing | 0.994 | D | 0.727 | deleterious | None | None | None | None | N |
| R/K | 0.1661 | likely_benign | 0.1444 | benign | -0.105 | Destabilizing | 0.817 | D | 0.433 | neutral | N | 0.43029967 | None | None | N |
| R/L | 0.4935 | ambiguous | 0.3291 | benign | 0.372 | Stabilizing | 0.935 | D | 0.635 | neutral | None | None | None | None | N |
| R/M | 0.5239 | ambiguous | 0.3777 | ambiguous | -0.136 | Destabilizing | 0.998 | D | 0.608 | neutral | N | 0.463969526 | None | None | N |
| R/N | 0.7763 | likely_pathogenic | 0.6625 | pathogenic | 0.006 | Stabilizing | 0.978 | D | 0.513 | neutral | None | None | None | None | N |
| R/P | 0.4399 | ambiguous | 0.312 | benign | 0.227 | Stabilizing | 0.009 | N | 0.343 | neutral | None | None | None | None | N |
| R/Q | 0.18 | likely_benign | 0.1289 | benign | -0.036 | Destabilizing | 0.978 | D | 0.543 | neutral | None | None | None | None | N |
| R/S | 0.7366 | likely_pathogenic | 0.5908 | pathogenic | -0.406 | Destabilizing | 0.915 | D | 0.538 | neutral | N | 0.417215729 | None | None | N |
| R/T | 0.5366 | ambiguous | 0.3803 | ambiguous | -0.171 | Destabilizing | 0.915 | D | 0.547 | neutral | N | 0.444343616 | None | None | N |
| R/V | 0.5904 | likely_pathogenic | 0.4626 | ambiguous | 0.227 | Stabilizing | 0.981 | D | 0.69 | prob.delet. | None | None | None | None | N |
| R/W | 0.4853 | ambiguous | 0.3268 | benign | -0.405 | Destabilizing | 0.998 | D | 0.704 | prob.delet. | N | 0.482902004 | None | None | N |
| R/Y | 0.6499 | likely_pathogenic | 0.5045 | ambiguous | 0.011 | Stabilizing | 0.994 | D | 0.67 | prob.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.