Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3061 | 9406;9407;9408 | chr2:178768138;178768137;178768136 | chr2:179632865;179632864;179632863 |
| N2AB | 3061 | 9406;9407;9408 | chr2:178768138;178768137;178768136 | chr2:179632865;179632864;179632863 |
| N2A | 3061 | 9406;9407;9408 | chr2:178768138;178768137;178768136 | chr2:179632865;179632864;179632863 |
| N2B | 3015 | 9268;9269;9270 | chr2:178768138;178768137;178768136 | chr2:179632865;179632864;179632863 |
| Novex-1 | 3015 | 9268;9269;9270 | chr2:178768138;178768137;178768136 | chr2:179632865;179632864;179632863 |
| Novex-2 | 3015 | 9268;9269;9270 | chr2:178768138;178768137;178768136 | chr2:179632865;179632864;179632863 |
| Novex-3 | 3061 | 9406;9407;9408 | chr2:178768138;178768137;178768136 | chr2:179632865;179632864;179632863 |
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 | rs561375563  |
-0.59 | 0.959 | D | 0.442 | 0.498 | 0.664136802156 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 6.15E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/G | rs561375563 |
-0.59 | 0.959 | D | 0.442 | 0.498 | 0.664136802156 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/G | rs561375563 |
-0.59 | 0.959 | D | 0.442 | 0.498 | 0.664136802156 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/G | rs561375563 |
-0.59 | 0.959 | D | 0.442 | 0.498 | 0.664136802156 | gnomAD-4.0.0 | 6.56426E-06 | None | None | None | None | N | None | 2.40535E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/S | rs773298764 |
-0.295 | 0.852 | N | 0.439 | 0.388 | 0.318252033908 | gnomAD-4.0.0 | 1.59071E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85657E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9499 | likely_pathogenic | 0.928 | pathogenic | -0.579 | Destabilizing | 0.863 | D | 0.428 | neutral | None | None | None | None | N |
| R/C | 0.5817 | likely_pathogenic | 0.5676 | pathogenic | -0.58 | Destabilizing | 0.999 | D | 0.433 | neutral | None | None | None | None | N |
| R/D | 0.9885 | likely_pathogenic | 0.9835 | pathogenic | 0.124 | Stabilizing | 0.969 | D | 0.421 | neutral | None | None | None | None | N |
| R/E | 0.8835 | likely_pathogenic | 0.8516 | pathogenic | 0.253 | Stabilizing | 0.969 | D | 0.434 | neutral | None | None | None | None | N |
| R/F | 0.9613 | likely_pathogenic | 0.9489 | pathogenic | -0.417 | Destabilizing | 0.997 | D | 0.425 | neutral | None | None | None | None | N |
| R/G | 0.8998 | likely_pathogenic | 0.8671 | pathogenic | -0.88 | Destabilizing | 0.959 | D | 0.442 | neutral | D | 0.533769733 | None | None | N |
| R/H | 0.3996 | ambiguous | 0.3487 | ambiguous | -1.19 | Destabilizing | 0.997 | D | 0.471 | neutral | None | None | None | None | N |
| R/I | 0.7448 | likely_pathogenic | 0.7003 | pathogenic | 0.222 | Stabilizing | 0.982 | D | 0.42 | neutral | None | None | None | None | N |
| R/K | 0.3074 | likely_benign | 0.2793 | benign | -0.489 | Destabilizing | 0.826 | D | 0.393 | neutral | N | 0.499257685 | None | None | N |
| R/L | 0.6647 | likely_pathogenic | 0.6154 | pathogenic | 0.222 | Stabilizing | 0.939 | D | 0.425 | neutral | None | None | None | None | N |
| R/M | 0.8319 | likely_pathogenic | 0.8006 | pathogenic | -0.231 | Destabilizing | 0.996 | D | 0.455 | neutral | N | 0.511897292 | None | None | N |
| R/N | 0.9643 | likely_pathogenic | 0.9545 | pathogenic | -0.107 | Destabilizing | 0.969 | D | 0.445 | neutral | None | None | None | None | N |
| R/P | 0.9893 | likely_pathogenic | 0.983 | pathogenic | -0.024 | Destabilizing | 0.997 | D | 0.424 | neutral | None | None | None | None | N |
| R/Q | 0.3079 | likely_benign | 0.2731 | benign | -0.213 | Destabilizing | 0.99 | D | 0.459 | neutral | None | None | None | None | N |
| R/S | 0.9561 | likely_pathogenic | 0.9374 | pathogenic | -0.816 | Destabilizing | 0.852 | D | 0.439 | neutral | N | 0.495682834 | None | None | N |
| R/T | 0.7839 | likely_pathogenic | 0.7375 | pathogenic | -0.501 | Destabilizing | 0.061 | N | 0.237 | neutral | N | 0.407453048 | None | None | N |
| R/V | 0.8053 | likely_pathogenic | 0.7698 | pathogenic | -0.024 | Destabilizing | 0.939 | D | 0.427 | neutral | None | None | None | None | N |
| R/W | 0.6291 | likely_pathogenic | 0.5794 | pathogenic | -0.152 | Destabilizing | 0.999 | D | 0.476 | neutral | D | 0.560503938 | None | None | N |
| R/Y | 0.9078 | likely_pathogenic | 0.8863 | pathogenic | 0.153 | Stabilizing | 0.997 | D | 0.435 | 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.