Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 34968 | 105127;105128;105129 | chr2:178531713;178531712;178531711 | chr2:179396440;179396439;179396438 |
| N2AB | 33327 | 100204;100205;100206 | chr2:178531713;178531712;178531711 | chr2:179396440;179396439;179396438 |
| N2A | 32400 | 97423;97424;97425 | chr2:178531713;178531712;178531711 | chr2:179396440;179396439;179396438 |
| N2B | 25903 | 77932;77933;77934 | chr2:178531713;178531712;178531711 | chr2:179396440;179396439;179396438 |
| Novex-1 | 26028 | 78307;78308;78309 | chr2:178531713;178531712;178531711 | chr2:179396440;179396439;179396438 |
| Novex-2 | 26095 | 78508;78509;78510 | chr2:178531713;178531712;178531711 | chr2:179396440;179396439;179396438 |
| 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/E | None | None | 0.999 | N | 0.685 | 0.471 | 0.405839309607 | gnomAD-4.0.0 | 1.59088E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43271E-05 | 0 |
| K/N | rs1274496471  |
-0.493 | 1.0 | N | 0.754 | 0.272 | 0.212008924253 | gnomAD-2.1.1 | 4.01E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.86E-06 | 0 |
| K/N | rs1274496471 |
-0.493 | 1.0 | N | 0.754 | 0.272 | 0.212008924253 | gnomAD-4.0.0 | 2.73656E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59759E-06 | 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 | 0.8613 | likely_pathogenic | 0.9469 | pathogenic | 0.003 | Stabilizing | 0.999 | D | 0.687 | prob.neutral | None | None | None | None | N |
| K/C | 0.9569 | likely_pathogenic | 0.9802 | pathogenic | -0.393 | Destabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | N |
| K/D | 0.9652 | likely_pathogenic | 0.9866 | pathogenic | -0.236 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | N |
| K/E | 0.7506 | likely_pathogenic | 0.9137 | pathogenic | -0.257 | Destabilizing | 0.999 | D | 0.685 | prob.neutral | N | 0.49677067 | None | None | N |
| K/F | 0.9721 | likely_pathogenic | 0.9907 | pathogenic | -0.368 | Destabilizing | 1.0 | D | 0.718 | prob.delet. | None | None | None | None | N |
| K/G | 0.9367 | likely_pathogenic | 0.978 | pathogenic | -0.114 | Destabilizing | 1.0 | D | 0.657 | neutral | None | None | None | None | N |
| K/H | 0.7092 | likely_pathogenic | 0.8328 | pathogenic | -0.247 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | N |
| K/I | 0.8023 | likely_pathogenic | 0.924 | pathogenic | 0.225 | Stabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | N |
| K/L | 0.7962 | likely_pathogenic | 0.9062 | pathogenic | 0.225 | Stabilizing | 1.0 | D | 0.657 | neutral | None | None | None | None | N |
| K/M | 0.6957 | likely_pathogenic | 0.8582 | pathogenic | -0.042 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | N | 0.510117368 | None | None | N |
| K/N | 0.8987 | likely_pathogenic | 0.9646 | pathogenic | 0.069 | Stabilizing | 1.0 | D | 0.754 | deleterious | N | 0.482380008 | None | None | N |
| K/P | 0.9518 | likely_pathogenic | 0.9746 | pathogenic | 0.174 | Stabilizing | 1.0 | D | 0.704 | prob.neutral | None | None | None | None | N |
| K/Q | 0.4719 | ambiguous | 0.7235 | pathogenic | -0.089 | Destabilizing | 1.0 | D | 0.751 | deleterious | N | 0.513972351 | None | None | N |
| K/R | 0.1543 | likely_benign | 0.232 | benign | -0.086 | Destabilizing | 0.999 | D | 0.613 | neutral | D | 0.526440216 | None | None | N |
| K/S | 0.889 | likely_pathogenic | 0.9585 | pathogenic | -0.31 | Destabilizing | 0.999 | D | 0.713 | prob.delet. | None | None | None | None | N |
| K/T | 0.7003 | likely_pathogenic | 0.8759 | pathogenic | -0.217 | Destabilizing | 1.0 | D | 0.692 | prob.neutral | N | 0.513278918 | None | None | N |
| K/V | 0.7757 | likely_pathogenic | 0.9 | pathogenic | 0.174 | Stabilizing | 1.0 | D | 0.702 | prob.neutral | None | None | None | None | N |
| K/W | 0.9728 | likely_pathogenic | 0.9904 | pathogenic | -0.463 | Destabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | N |
| K/Y | 0.9231 | likely_pathogenic | 0.9664 | pathogenic | -0.107 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | 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.