Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1133 | 3622;3623;3624 | chr2:178781247;178781246;178781245 | chr2:179645974;179645973;179645972 |
| N2AB | 1133 | 3622;3623;3624 | chr2:178781247;178781246;178781245 | chr2:179645974;179645973;179645972 |
| N2A | 1133 | 3622;3623;3624 | chr2:178781247;178781246;178781245 | chr2:179645974;179645973;179645972 |
| N2B | 1087 | 3484;3485;3486 | chr2:178781247;178781246;178781245 | chr2:179645974;179645973;179645972 |
| Novex-1 | 1087 | 3484;3485;3486 | chr2:178781247;178781246;178781245 | chr2:179645974;179645973;179645972 |
| Novex-2 | 1087 | 3484;3485;3486 | chr2:178781247;178781246;178781245 | chr2:179645974;179645973;179645972 |
| Novex-3 | 1133 | 3622;3623;3624 | chr2:178781247;178781246;178781245 | chr2:179645974;179645973;179645972 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/S | rs775192919  |
-0.512 | 0.027 | N | 0.329 | 0.146 | 0.198526703765 | gnomAD-2.1.1 | 1.99E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.63345E-04 | None | 0 | 0 | 0 |
| N/S | rs775192919 |
-0.512 | 0.027 | N | 0.329 | 0.146 | 0.198526703765 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 4.14079E-04 | 0 |
| N/S | rs775192919 |
-0.512 | 0.027 | N | 0.329 | 0.146 | 0.198526703765 | gnomAD-4.0.0 | 4.60988E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 4.82444E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.4467 | ambiguous | 0.4482 | ambiguous | -0.792 | Destabilizing | 0.067 | N | 0.323 | neutral | None | None | None | None | N |
| N/C | 0.4807 | ambiguous | 0.4635 | ambiguous | 0.183 | Stabilizing | 0.935 | D | 0.407 | neutral | None | None | None | None | N |
| N/D | 0.0987 | likely_benign | 0.0903 | benign | -0.334 | Destabilizing | None | N | 0.097 | neutral | N | 0.449136464 | None | None | N |
| N/E | 0.4418 | ambiguous | 0.4362 | ambiguous | -0.305 | Destabilizing | 0.035 | N | 0.291 | neutral | None | None | None | None | N |
| N/F | 0.8397 | likely_pathogenic | 0.8369 | pathogenic | -0.817 | Destabilizing | 0.791 | D | 0.382 | neutral | None | None | None | None | N |
| N/G | 0.6229 | likely_pathogenic | 0.6058 | pathogenic | -1.065 | Destabilizing | 0.067 | N | 0.273 | neutral | None | None | None | None | N |
| N/H | 0.1534 | likely_benign | 0.146 | benign | -0.984 | Destabilizing | 0.484 | N | 0.337 | neutral | N | 0.511884273 | None | None | N |
| N/I | 0.3627 | ambiguous | 0.3775 | ambiguous | -0.127 | Destabilizing | 0.484 | N | 0.411 | neutral | N | 0.512759928 | None | None | N |
| N/K | 0.465 | ambiguous | 0.4429 | ambiguous | -0.222 | Destabilizing | None | N | 0.077 | neutral | N | 0.499112713 | None | None | N |
| N/L | 0.3737 | ambiguous | 0.3847 | ambiguous | -0.127 | Destabilizing | 0.149 | N | 0.365 | neutral | None | None | None | None | N |
| N/M | 0.5532 | ambiguous | 0.5667 | pathogenic | 0.458 | Stabilizing | 0.935 | D | 0.347 | neutral | None | None | None | None | N |
| N/P | 0.9469 | likely_pathogenic | 0.9383 | pathogenic | -0.32 | Destabilizing | 0.555 | D | 0.366 | neutral | None | None | None | None | N |
| N/Q | 0.3991 | ambiguous | 0.3925 | ambiguous | -0.778 | Destabilizing | 0.149 | N | 0.289 | neutral | None | None | None | None | N |
| N/R | 0.528 | ambiguous | 0.5054 | ambiguous | -0.176 | Destabilizing | 0.001 | N | 0.154 | neutral | None | None | None | None | N |
| N/S | 0.1048 | likely_benign | 0.104 | benign | -0.638 | Destabilizing | 0.027 | N | 0.329 | neutral | N | 0.484543749 | None | None | N |
| N/T | 0.2684 | likely_benign | 0.27 | benign | -0.435 | Destabilizing | 0.117 | N | 0.248 | neutral | N | 0.489558064 | None | None | N |
| N/V | 0.3645 | ambiguous | 0.3768 | ambiguous | -0.32 | Destabilizing | 0.555 | D | 0.402 | neutral | None | None | None | None | N |
| N/W | 0.9196 | likely_pathogenic | 0.9139 | pathogenic | -0.631 | Destabilizing | 0.935 | D | 0.481 | neutral | None | None | None | None | N |
| N/Y | 0.4078 | ambiguous | 0.3965 | ambiguous | -0.438 | Destabilizing | 0.741 | D | 0.371 | neutral | D | 0.548054477 | 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.