Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22694 | 68305;68306;68307 | chr2:178578950;178578949;178578948 | chr2:179443677;179443676;179443675 |
| N2AB | 21053 | 63382;63383;63384 | chr2:178578950;178578949;178578948 | chr2:179443677;179443676;179443675 |
| N2A | 20126 | 60601;60602;60603 | chr2:178578950;178578949;178578948 | chr2:179443677;179443676;179443675 |
| N2B | 13629 | 41110;41111;41112 | chr2:178578950;178578949;178578948 | chr2:179443677;179443676;179443675 |
| Novex-1 | 13754 | 41485;41486;41487 | chr2:178578950;178578949;178578948 | chr2:179443677;179443676;179443675 |
| Novex-2 | 13821 | 41686;41687;41688 | chr2:178578950;178578949;178578948 | chr2:179443677;179443676;179443675 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/Y | rs756052769  |
-1.229 | 0.873 | N | 0.581 | 0.351 | 0.580770577012 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 0 | 0 |
| C/Y | rs756052769 |
-1.229 | 0.873 | N | 0.581 | 0.351 | 0.580770577012 | gnomAD-4.0.0 | 4.10642E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.73611E-04 | 1.79934E-06 | 3.47818E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/A | 0.343 | ambiguous | 0.3747 | ambiguous | -1.426 | Destabilizing | 0.103 | N | 0.303 | neutral | None | None | None | None | N |
| C/D | 0.9735 | likely_pathogenic | 0.9737 | pathogenic | 0.285 | Stabilizing | 0.561 | D | 0.539 | neutral | None | None | None | None | N |
| C/E | 0.978 | likely_pathogenic | 0.9752 | pathogenic | 0.379 | Stabilizing | 0.561 | D | 0.537 | neutral | None | None | None | None | N |
| C/F | 0.4641 | ambiguous | 0.4009 | ambiguous | -0.932 | Destabilizing | 0.772 | D | 0.579 | neutral | N | 0.4642976 | None | None | N |
| C/G | 0.4179 | ambiguous | 0.4551 | ambiguous | -1.71 | Destabilizing | 0.491 | N | 0.506 | neutral | N | 0.463998497 | None | None | N |
| C/H | 0.9107 | likely_pathogenic | 0.8965 | pathogenic | -1.609 | Destabilizing | 0.991 | D | 0.589 | neutral | None | None | None | None | N |
| C/I | 0.4044 | ambiguous | 0.3712 | ambiguous | -0.714 | Destabilizing | 0.209 | N | 0.415 | neutral | None | None | None | None | N |
| C/K | 0.9882 | likely_pathogenic | 0.9858 | pathogenic | -0.403 | Destabilizing | 0.561 | D | 0.533 | neutral | None | None | None | None | N |
| C/L | 0.4952 | ambiguous | 0.4856 | ambiguous | -0.714 | Destabilizing | 0.103 | N | 0.374 | neutral | None | None | None | None | N |
| C/M | 0.6334 | likely_pathogenic | 0.6203 | pathogenic | -0.037 | Destabilizing | 0.901 | D | 0.54 | neutral | None | None | None | None | N |
| C/N | 0.8445 | likely_pathogenic | 0.8456 | pathogenic | -0.483 | Destabilizing | 0.818 | D | 0.588 | neutral | None | None | None | None | N |
| C/P | 0.9746 | likely_pathogenic | 0.9833 | pathogenic | -0.925 | Destabilizing | 0.901 | D | 0.586 | neutral | None | None | None | None | N |
| C/Q | 0.9424 | likely_pathogenic | 0.9356 | pathogenic | -0.343 | Destabilizing | 0.901 | D | 0.589 | neutral | None | None | None | None | N |
| C/R | 0.9383 | likely_pathogenic | 0.9229 | pathogenic | -0.339 | Destabilizing | 0.873 | D | 0.59 | neutral | N | 0.462224071 | None | None | N |
| C/S | 0.346 | ambiguous | 0.3782 | ambiguous | -1.032 | Destabilizing | 0.036 | N | 0.247 | neutral | N | 0.493351071 | None | None | N |
| C/T | 0.4174 | ambiguous | 0.4447 | ambiguous | -0.743 | Destabilizing | 0.209 | N | 0.427 | neutral | None | None | None | None | N |
| C/V | 0.2479 | likely_benign | 0.2365 | benign | -0.925 | Destabilizing | 0.001 | N | 0.285 | neutral | None | None | None | None | N |
| C/W | 0.8716 | likely_pathogenic | 0.8473 | pathogenic | -0.901 | Destabilizing | 0.995 | D | 0.598 | neutral | N | 0.50578165 | None | None | N |
| C/Y | 0.703 | likely_pathogenic | 0.6309 | pathogenic | -0.848 | Destabilizing | 0.873 | D | 0.581 | neutral | N | 0.5047415 | 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.