Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29550 | 88873;88874;88875 | chr2:178554699;178554698;178554697 | chr2:179419426;179419425;179419424 |
| N2AB | 27909 | 83950;83951;83952 | chr2:178554699;178554698;178554697 | chr2:179419426;179419425;179419424 |
| N2A | 26982 | 81169;81170;81171 | chr2:178554699;178554698;178554697 | chr2:179419426;179419425;179419424 |
| N2B | 20485 | 61678;61679;61680 | chr2:178554699;178554698;178554697 | chr2:179419426;179419425;179419424 |
| Novex-1 | 20610 | 62053;62054;62055 | chr2:178554699;178554698;178554697 | chr2:179419426;179419425;179419424 |
| Novex-2 | 20677 | 62254;62255;62256 | chr2:178554699;178554698;178554697 | chr2:179419426;179419425;179419424 |
| 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/M | rs750362797  |
-0.091 | 0.999 | N | 0.565 | 0.482 | 0.353125101423 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| K/M | rs750362797 |
-0.091 | 0.999 | N | 0.565 | 0.482 | 0.353125101423 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| K/M | rs750362797 |
-0.091 | 0.999 | N | 0.565 | 0.482 | 0.353125101423 | gnomAD-4.0.0 | 1.85893E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.5427E-06 | 0 | 0 |
| K/N | rs778800874 |
-0.897 | 0.061 | N | 0.197 | 0.082 | 0.151104730317 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| K/N | rs778800874 |
-0.897 | 0.061 | N | 0.197 | 0.082 | 0.151104730317 | gnomAD-4.0.0 | 1.36834E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79886E-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 | 0.8652 | likely_pathogenic | 0.8852 | pathogenic | -0.648 | Destabilizing | 0.863 | D | 0.457 | neutral | None | None | None | None | N |
| K/C | 0.9089 | likely_pathogenic | 0.9166 | pathogenic | -0.829 | Destabilizing | 0.999 | D | 0.602 | neutral | None | None | None | None | N |
| K/D | 0.9144 | likely_pathogenic | 0.9323 | pathogenic | -0.363 | Destabilizing | 0.884 | D | 0.479 | neutral | None | None | None | None | N |
| K/E | 0.7758 | likely_pathogenic | 0.7936 | pathogenic | -0.268 | Destabilizing | 0.92 | D | 0.5 | neutral | N | 0.476170819 | None | None | N |
| K/F | 0.9691 | likely_pathogenic | 0.975 | pathogenic | -0.523 | Destabilizing | 0.997 | D | 0.594 | neutral | None | None | None | None | N |
| K/G | 0.8681 | likely_pathogenic | 0.8934 | pathogenic | -0.991 | Destabilizing | 0.939 | D | 0.509 | neutral | None | None | None | None | N |
| K/H | 0.5624 | ambiguous | 0.5897 | pathogenic | -1.375 | Destabilizing | 0.991 | D | 0.572 | neutral | None | None | None | None | N |
| K/I | 0.893 | likely_pathogenic | 0.9079 | pathogenic | 0.231 | Stabilizing | 0.982 | D | 0.597 | neutral | None | None | None | None | N |
| K/L | 0.8661 | likely_pathogenic | 0.8895 | pathogenic | 0.231 | Stabilizing | 0.939 | D | 0.521 | neutral | None | None | None | None | N |
| K/M | 0.6621 | likely_pathogenic | 0.6892 | pathogenic | 0.206 | Stabilizing | 0.999 | D | 0.565 | neutral | N | 0.502858775 | None | None | N |
| K/N | 0.7777 | likely_pathogenic | 0.8154 | pathogenic | -0.541 | Destabilizing | 0.061 | N | 0.197 | neutral | N | 0.442194319 | None | None | N |
| K/P | 0.9955 | likely_pathogenic | 0.997 | pathogenic | -0.033 | Destabilizing | 0.997 | D | 0.588 | neutral | None | None | None | None | N |
| K/Q | 0.4528 | ambiguous | 0.4959 | ambiguous | -0.717 | Destabilizing | 0.988 | D | 0.521 | neutral | N | 0.4753441 | None | None | N |
| K/R | 0.1256 | likely_benign | 0.1421 | benign | -0.574 | Destabilizing | 0.959 | D | 0.497 | neutral | N | 0.458990568 | None | None | N |
| K/S | 0.8466 | likely_pathogenic | 0.871 | pathogenic | -1.23 | Destabilizing | 0.759 | D | 0.465 | neutral | None | None | None | None | N |
| K/T | 0.6045 | likely_pathogenic | 0.631 | pathogenic | -0.935 | Destabilizing | 0.134 | N | 0.333 | neutral | N | 0.422336334 | None | None | N |
| K/V | 0.8423 | likely_pathogenic | 0.8617 | pathogenic | -0.033 | Destabilizing | 0.939 | D | 0.562 | neutral | None | None | None | None | N |
| K/W | 0.9501 | likely_pathogenic | 0.9602 | pathogenic | -0.374 | Destabilizing | 0.999 | D | 0.64 | neutral | None | None | None | None | N |
| K/Y | 0.8751 | likely_pathogenic | 0.893 | pathogenic | -0.03 | Destabilizing | 0.997 | D | 0.577 | 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.