Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 34985 | 105178;105179;105180 | chr2:178531662;178531661;178531660 | chr2:179396389;179396388;179396387 |
| N2AB | 33344 | 100255;100256;100257 | chr2:178531662;178531661;178531660 | chr2:179396389;179396388;179396387 |
| N2A | 32417 | 97474;97475;97476 | chr2:178531662;178531661;178531660 | chr2:179396389;179396388;179396387 |
| N2B | 25920 | 77983;77984;77985 | chr2:178531662;178531661;178531660 | chr2:179396389;179396388;179396387 |
| Novex-1 | 26045 | 78358;78359;78360 | chr2:178531662;178531661;178531660 | chr2:179396389;179396388;179396387 |
| Novex-2 | 26112 | 78559;78560;78561 | chr2:178531662;178531661;178531660 | chr2:179396389;179396388;179396387 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/G | rs765030518  |
-0.417 | 0.994 | N | 0.409 | 0.215 | 0.144782658237 | gnomAD-2.1.1 | 2.41E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.56E-05 | None | 0 | None | 0 | 3.54E-05 | 1.65289E-04 |
| S/G | rs765030518 |
-0.417 | 0.994 | N | 0.409 | 0.215 | 0.144782658237 | gnomAD-4.0.0 | 2.3945E-05 | None | None | None | None | N | None | 2.98704E-05 | 0 | None | 0 | 2.51889E-05 | None | 0 | 0 | 2.96802E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.2884 | likely_benign | 0.312 | benign | -0.162 | Destabilizing | 0.99 | D | 0.453 | neutral | None | None | None | None | N |
| S/C | 0.277 | likely_benign | 0.3337 | benign | -0.279 | Destabilizing | 1.0 | D | 0.509 | neutral | N | 0.4944392 | None | None | N |
| S/D | 0.6454 | likely_pathogenic | 0.6783 | pathogenic | 0.283 | Stabilizing | 0.269 | N | 0.291 | neutral | None | None | None | None | N |
| S/E | 0.9202 | likely_pathogenic | 0.9343 | pathogenic | 0.185 | Stabilizing | 0.983 | D | 0.398 | neutral | None | None | None | None | N |
| S/F | 0.8321 | likely_pathogenic | 0.8649 | pathogenic | -0.839 | Destabilizing | 1.0 | D | 0.557 | neutral | None | None | None | None | N |
| S/G | 0.1632 | likely_benign | 0.1848 | benign | -0.244 | Destabilizing | 0.994 | D | 0.409 | neutral | N | 0.438950865 | None | None | N |
| S/H | 0.7778 | likely_pathogenic | 0.8115 | pathogenic | -0.669 | Destabilizing | 1.0 | D | 0.483 | neutral | None | None | None | None | N |
| S/I | 0.8491 | likely_pathogenic | 0.8647 | pathogenic | -0.082 | Destabilizing | 0.999 | D | 0.541 | neutral | N | 0.47624604 | None | None | N |
| S/K | 0.9762 | likely_pathogenic | 0.9789 | pathogenic | -0.326 | Destabilizing | 0.996 | D | 0.417 | neutral | None | None | None | None | N |
| S/L | 0.5725 | likely_pathogenic | 0.5971 | pathogenic | -0.082 | Destabilizing | 1.0 | D | 0.489 | neutral | None | None | None | None | N |
| S/M | 0.7073 | likely_pathogenic | 0.7277 | pathogenic | -0.026 | Destabilizing | 1.0 | D | 0.497 | neutral | None | None | None | None | N |
| S/N | 0.3279 | likely_benign | 0.3466 | ambiguous | -0.094 | Destabilizing | 0.989 | D | 0.417 | neutral | N | 0.473546228 | None | None | N |
| S/P | 0.9735 | likely_pathogenic | 0.9747 | pathogenic | -0.081 | Destabilizing | 1.0 | D | 0.475 | neutral | None | None | None | None | N |
| S/Q | 0.9178 | likely_pathogenic | 0.9344 | pathogenic | -0.298 | Destabilizing | 0.999 | D | 0.476 | neutral | None | None | None | None | N |
| S/R | 0.9641 | likely_pathogenic | 0.971 | pathogenic | -0.142 | Destabilizing | 0.998 | D | 0.461 | neutral | N | 0.466673707 | None | None | N |
| S/T | 0.1502 | likely_benign | 0.1531 | benign | -0.195 | Destabilizing | 0.994 | D | 0.419 | neutral | N | 0.495076293 | None | None | N |
| S/V | 0.7882 | likely_pathogenic | 0.8063 | pathogenic | -0.081 | Destabilizing | 1.0 | D | 0.528 | neutral | None | None | None | None | N |
| S/W | 0.901 | likely_pathogenic | 0.9223 | pathogenic | -0.908 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | N |
| S/Y | 0.7485 | likely_pathogenic | 0.7849 | pathogenic | -0.587 | Destabilizing | 1.0 | D | 0.557 | 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.