Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14255 | 42988;42989;42990 | chr2:178633596;178633595;178633594 | chr2:179498323;179498322;179498321 |
| N2AB | 12614 | 38065;38066;38067 | chr2:178633596;178633595;178633594 | chr2:179498323;179498322;179498321 |
| N2A | 11687 | 35284;35285;35286 | chr2:178633596;178633595;178633594 | chr2:179498323;179498322;179498321 |
| N2B | 5190 | 15793;15794;15795 | chr2:178633596;178633595;178633594 | chr2:179498323;179498322;179498321 |
| Novex-1 | 5315 | 16168;16169;16170 | chr2:178633596;178633595;178633594 | chr2:179498323;179498322;179498321 |
| Novex-2 | 5382 | 16369;16370;16371 | chr2:178633596;178633595;178633594 | chr2:179498323;179498322;179498321 |
| 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/N | rs368433387  |
-0.383 | 0.058 | D | 0.141 | 0.253 | None | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/N | rs368433387 |
-0.383 | 0.058 | D | 0.141 | 0.253 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/N | rs368433387 |
-0.383 | 0.058 | D | 0.141 | 0.253 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| S/N | rs368433387 |
-0.383 | 0.058 | D | 0.141 | 0.253 | None | gnomAD-4.0.0 | 5.07429E-06 | None | None | None | None | N | None | 6.9752E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.39997E-05 |
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 | 0.4444 | ambiguous | 0.4436 | ambiguous | -0.496 | Destabilizing | 0.717 | D | 0.44 | neutral | None | None | None | None | N |
| S/C | 0.6214 | likely_pathogenic | 0.6629 | pathogenic | -0.311 | Destabilizing | 0.997 | D | 0.482 | neutral | D | 0.681298195 | None | None | N |
| S/D | 0.9018 | likely_pathogenic | 0.9235 | pathogenic | 0.31 | Stabilizing | 0.754 | D | 0.375 | neutral | None | None | None | None | N |
| S/E | 0.965 | likely_pathogenic | 0.9641 | pathogenic | 0.329 | Stabilizing | 0.86 | D | 0.381 | neutral | None | None | None | None | N |
| S/F | 0.9477 | likely_pathogenic | 0.9425 | pathogenic | -0.592 | Destabilizing | 0.993 | D | 0.528 | neutral | None | None | None | None | N |
| S/G | 0.3903 | ambiguous | 0.4253 | ambiguous | -0.76 | Destabilizing | 0.656 | D | 0.429 | neutral | D | 0.597306001 | None | None | N |
| S/H | 0.9204 | likely_pathogenic | 0.9242 | pathogenic | -1.087 | Destabilizing | 0.978 | D | 0.452 | neutral | None | None | None | None | N |
| S/I | 0.8723 | likely_pathogenic | 0.8528 | pathogenic | 0.1 | Stabilizing | 0.97 | D | 0.529 | neutral | D | 0.618862251 | None | None | N |
| S/K | 0.992 | likely_pathogenic | 0.9915 | pathogenic | -0.384 | Destabilizing | 0.754 | D | 0.39 | neutral | None | None | None | None | N |
| S/L | 0.7481 | likely_pathogenic | 0.7278 | pathogenic | 0.1 | Stabilizing | 0.86 | D | 0.455 | neutral | None | None | None | None | N |
| S/M | 0.8457 | likely_pathogenic | 0.8326 | pathogenic | 0.086 | Stabilizing | 0.998 | D | 0.454 | neutral | None | None | None | None | N |
| S/N | 0.5292 | ambiguous | 0.5706 | pathogenic | -0.374 | Destabilizing | 0.058 | N | 0.141 | neutral | D | 0.553873982 | None | None | N |
| S/P | 0.9773 | likely_pathogenic | 0.9762 | pathogenic | -0.064 | Destabilizing | 0.993 | D | 0.431 | neutral | None | None | None | None | N |
| S/Q | 0.9545 | likely_pathogenic | 0.9564 | pathogenic | -0.416 | Destabilizing | 0.956 | D | 0.403 | neutral | None | None | None | None | N |
| S/R | 0.9826 | likely_pathogenic | 0.9818 | pathogenic | -0.361 | Destabilizing | 0.032 | N | 0.285 | neutral | D | 0.578625695 | None | None | N |
| S/T | 0.3816 | ambiguous | 0.38 | ambiguous | -0.406 | Destabilizing | 0.822 | D | 0.422 | neutral | N | 0.509458945 | None | None | N |
| S/V | 0.871 | likely_pathogenic | 0.8579 | pathogenic | -0.064 | Destabilizing | 0.978 | D | 0.49 | neutral | None | None | None | None | N |
| S/W | 0.9498 | likely_pathogenic | 0.9487 | pathogenic | -0.623 | Destabilizing | 0.998 | D | 0.616 | neutral | None | None | None | None | N |
| S/Y | 0.8819 | likely_pathogenic | 0.8797 | pathogenic | -0.316 | Destabilizing | 0.993 | D | 0.529 | 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.