Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17779 | 53560;53561;53562 | chr2:178607267;178607266;178607265 | chr2:179471994;179471993;179471992 |
| N2AB | 16138 | 48637;48638;48639 | chr2:178607267;178607266;178607265 | chr2:179471994;179471993;179471992 |
| N2A | 15211 | 45856;45857;45858 | chr2:178607267;178607266;178607265 | chr2:179471994;179471993;179471992 |
| N2B | 8714 | 26365;26366;26367 | chr2:178607267;178607266;178607265 | chr2:179471994;179471993;179471992 |
| Novex-1 | 8839 | 26740;26741;26742 | chr2:178607267;178607266;178607265 | chr2:179471994;179471993;179471992 |
| Novex-2 | 8906 | 26941;26942;26943 | chr2:178607267;178607266;178607265 | chr2:179471994;179471993;179471992 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/N | rs374831529  |
-0.315 | 1.0 | N | 0.683 | 0.284 | 0.158396225186 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| K/R | rs1402899150 |
-0.423 | 0.999 | N | 0.58 | 0.305 | 0.323342291347 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 2.91E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| K/R | rs1402899150 |
-0.423 | 0.999 | N | 0.58 | 0.305 | 0.323342291347 | gnomAD-4.0.0 | 3.18713E-06 | None | None | None | None | N | None | 0 | 4.57917E-05 | None | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.9329 | likely_pathogenic | 0.9052 | pathogenic | -0.467 | Destabilizing | 0.999 | D | 0.667 | neutral | None | None | None | None | N |
| K/C | 0.9562 | likely_pathogenic | 0.9389 | pathogenic | -0.613 | Destabilizing | 1.0 | D | 0.675 | prob.neutral | None | None | None | None | N |
| K/D | 0.9357 | likely_pathogenic | 0.9189 | pathogenic | -0.78 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | N |
| K/E | 0.8351 | likely_pathogenic | 0.7802 | pathogenic | -0.708 | Destabilizing | 0.999 | D | 0.593 | neutral | N | 0.436383067 | None | None | N |
| K/F | 0.9834 | likely_pathogenic | 0.9731 | pathogenic | -0.419 | Destabilizing | 1.0 | D | 0.67 | neutral | None | None | None | None | N |
| K/G | 0.9214 | likely_pathogenic | 0.9 | pathogenic | -0.796 | Destabilizing | 1.0 | D | 0.673 | neutral | None | None | None | None | N |
| K/H | 0.6978 | likely_pathogenic | 0.6148 | pathogenic | -1.29 | Destabilizing | 1.0 | D | 0.615 | neutral | None | None | None | None | N |
| K/I | 0.951 | likely_pathogenic | 0.9251 | pathogenic | 0.37 | Stabilizing | 1.0 | D | 0.7 | prob.neutral | N | 0.479597991 | None | None | N |
| K/L | 0.8989 | likely_pathogenic | 0.8611 | pathogenic | 0.37 | Stabilizing | 1.0 | D | 0.673 | neutral | None | None | None | None | N |
| K/M | 0.8416 | likely_pathogenic | 0.7761 | pathogenic | 0.443 | Stabilizing | 1.0 | D | 0.608 | neutral | None | None | None | None | N |
| K/N | 0.8809 | likely_pathogenic | 0.8246 | pathogenic | -0.64 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | N | 0.419218672 | None | None | N |
| K/P | 0.9922 | likely_pathogenic | 0.9922 | pathogenic | 0.121 | Stabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | N |
| K/Q | 0.5366 | ambiguous | 0.4395 | ambiguous | -0.842 | Destabilizing | 1.0 | D | 0.666 | neutral | N | 0.49131363 | None | None | N |
| K/R | 0.1466 | likely_benign | 0.1363 | benign | -0.661 | Destabilizing | 0.999 | D | 0.58 | neutral | N | 0.444559833 | None | None | N |
| K/S | 0.9245 | likely_pathogenic | 0.886 | pathogenic | -1.154 | Destabilizing | 0.999 | D | 0.655 | neutral | None | None | None | None | N |
| K/T | 0.7897 | likely_pathogenic | 0.7122 | pathogenic | -0.902 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | N | 0.417637017 | None | None | N |
| K/V | 0.9268 | likely_pathogenic | 0.8901 | pathogenic | 0.121 | Stabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | N |
| K/W | 0.9722 | likely_pathogenic | 0.9623 | pathogenic | -0.358 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| K/Y | 0.9244 | likely_pathogenic | 0.9032 | pathogenic | 0.003 | Stabilizing | 1.0 | D | 0.665 | 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.