Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2533 | 7822;7823;7824 | chr2:178773367;178773366;178773365 | chr2:179638094;179638093;179638092 |
| N2AB | 2533 | 7822;7823;7824 | chr2:178773367;178773366;178773365 | chr2:179638094;179638093;179638092 |
| N2A | 2533 | 7822;7823;7824 | chr2:178773367;178773366;178773365 | chr2:179638094;179638093;179638092 |
| N2B | 2487 | 7684;7685;7686 | chr2:178773367;178773366;178773365 | chr2:179638094;179638093;179638092 |
| Novex-1 | 2487 | 7684;7685;7686 | chr2:178773367;178773366;178773365 | chr2:179638094;179638093;179638092 |
| Novex-2 | 2487 | 7684;7685;7686 | chr2:178773367;178773366;178773365 | chr2:179638094;179638093;179638092 |
| Novex-3 | 2533 | 7822;7823;7824 | chr2:178773367;178773366;178773365 | chr2:179638094;179638093;179638092 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | None | None | 0.994 | D | 0.377 | 0.351 | 0.696815536761 | gnomAD-4.0.0 | 1.59087E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43287E-05 | 0 |
| I/N | rs1247030843  |
-0.292 | 0.998 | D | 0.511 | 0.593 | 0.890540186608 | gnomAD-2.1.1 | 4.01E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/N | rs1247030843 |
-0.292 | 0.998 | D | 0.511 | 0.593 | 0.890540186608 | gnomAD-4.0.0 | 1.59088E-06 | None | None | None | None | N | None | 0 | 2.28728E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs372407708 |
-0.368 | 0.044 | N | 0.159 | 0.084 | None | gnomAD-2.1.1 | 2.14E-05 | None | None | None | None | N | None | 2.47975E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs372407708 |
-0.368 | 0.044 | N | 0.159 | 0.084 | None | gnomAD-3.1.2 | 6.57E-05 | None | None | None | None | N | None | 2.41289E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs372407708 |
-0.368 | 0.044 | N | 0.159 | 0.084 | None | gnomAD-4.0.0 | 1.11524E-05 | None | None | None | None | N | None | 2.39866E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.8437 | likely_pathogenic | 0.8029 | pathogenic | -1.309 | Destabilizing | 0.931 | D | 0.346 | neutral | None | None | None | None | N |
| I/C | 0.9245 | likely_pathogenic | 0.8998 | pathogenic | -0.755 | Destabilizing | 1.0 | D | 0.377 | neutral | None | None | None | None | N |
| I/D | 0.9776 | likely_pathogenic | 0.969 | pathogenic | -0.665 | Destabilizing | 0.999 | D | 0.515 | neutral | None | None | None | None | N |
| I/E | 0.9275 | likely_pathogenic | 0.9083 | pathogenic | -0.673 | Destabilizing | 0.999 | D | 0.501 | neutral | None | None | None | None | N |
| I/F | 0.5827 | likely_pathogenic | 0.5214 | ambiguous | -0.921 | Destabilizing | 0.994 | D | 0.357 | neutral | D | 0.546979959 | None | None | N |
| I/G | 0.9535 | likely_pathogenic | 0.9354 | pathogenic | -1.608 | Destabilizing | 0.999 | D | 0.473 | neutral | None | None | None | None | N |
| I/H | 0.9554 | likely_pathogenic | 0.9398 | pathogenic | -0.835 | Destabilizing | 1.0 | D | 0.525 | neutral | None | None | None | None | N |
| I/K | 0.8894 | likely_pathogenic | 0.8593 | pathogenic | -0.841 | Destabilizing | 0.999 | D | 0.505 | neutral | None | None | None | None | N |
| I/L | 0.2774 | likely_benign | 0.2537 | benign | -0.577 | Destabilizing | 0.689 | D | 0.204 | neutral | N | 0.474772832 | None | None | N |
| I/M | 0.2376 | likely_benign | 0.2057 | benign | -0.508 | Destabilizing | 0.994 | D | 0.377 | neutral | D | 0.546567035 | None | None | N |
| I/N | 0.7553 | likely_pathogenic | 0.6929 | pathogenic | -0.597 | Destabilizing | 0.998 | D | 0.511 | neutral | D | 0.548580169 | None | None | N |
| I/P | 0.9029 | likely_pathogenic | 0.8941 | pathogenic | -0.789 | Destabilizing | 0.999 | D | 0.518 | neutral | None | None | None | None | N |
| I/Q | 0.9037 | likely_pathogenic | 0.875 | pathogenic | -0.746 | Destabilizing | 0.999 | D | 0.513 | neutral | None | None | None | None | N |
| I/R | 0.8614 | likely_pathogenic | 0.8225 | pathogenic | -0.314 | Destabilizing | 0.999 | D | 0.51 | neutral | None | None | None | None | N |
| I/S | 0.8406 | likely_pathogenic | 0.7907 | pathogenic | -1.17 | Destabilizing | 0.994 | D | 0.413 | neutral | D | 0.548035062 | None | None | N |
| I/T | 0.7584 | likely_pathogenic | 0.7115 | pathogenic | -1.055 | Destabilizing | 0.961 | D | 0.327 | neutral | D | 0.546979959 | None | None | N |
| I/V | 0.137 | likely_benign | 0.1272 | benign | -0.789 | Destabilizing | 0.044 | N | 0.159 | neutral | N | 0.413823846 | None | None | N |
| I/W | 0.9725 | likely_pathogenic | 0.9607 | pathogenic | -0.98 | Destabilizing | 1.0 | D | 0.604 | neutral | None | None | None | None | N |
| I/Y | 0.8721 | likely_pathogenic | 0.8433 | pathogenic | -0.753 | Destabilizing | 0.999 | D | 0.361 | 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.