Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 953 | 3082;3083;3084 | chr2:178783049;178783048;178783047 | chr2:179647776;179647775;179647774 |
| N2AB | 953 | 3082;3083;3084 | chr2:178783049;178783048;178783047 | chr2:179647776;179647775;179647774 |
| N2A | 953 | 3082;3083;3084 | chr2:178783049;178783048;178783047 | chr2:179647776;179647775;179647774 |
| N2B | 907 | 2944;2945;2946 | chr2:178783049;178783048;178783047 | chr2:179647776;179647775;179647774 |
| Novex-1 | 907 | 2944;2945;2946 | chr2:178783049;178783048;178783047 | chr2:179647776;179647775;179647774 |
| Novex-2 | 907 | 2944;2945;2946 | chr2:178783049;178783048;178783047 | chr2:179647776;179647775;179647774 |
| Novex-3 | 953 | 3082;3083;3084 | chr2:178783049;178783048;178783047 | chr2:179647776;179647775;179647774 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | None | None | 0.977 | N | 0.421 | 0.432 | 0.317958651998 | gnomAD-4.0.0 | 2.05228E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69796E-06 | 0 | 0 |
| T/P | None | None | 0.999 | N | 0.615 | 0.662 | 0.592512737887 | gnomAD-4.0.0 | 1.77864E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.33823E-05 | 0 | 0 |
| T/S | rs72647865  |
-0.223 | 0.989 | N | 0.453 | 0.357 | 0.294918367191 | gnomAD-2.1.1 | 4E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| T/S | rs72647865 |
-0.223 | 0.989 | N | 0.453 | 0.357 | 0.294918367191 | gnomAD-4.0.0 | 6.84097E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.8721E-05 | 0 | 6.29527E-06 | 1.15931E-05 | 1.6559E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.2353 | likely_benign | 0.2236 | benign | -0.305 | Destabilizing | 0.977 | D | 0.421 | neutral | N | 0.50345087 | None | None | N |
| T/C | 0.873 | likely_pathogenic | 0.8572 | pathogenic | -0.408 | Destabilizing | 1.0 | D | 0.596 | neutral | None | None | None | None | N |
| T/D | 0.7737 | likely_pathogenic | 0.7563 | pathogenic | 0.166 | Stabilizing | 0.999 | D | 0.628 | neutral | None | None | None | None | N |
| T/E | 0.655 | likely_pathogenic | 0.6262 | pathogenic | 0.118 | Stabilizing | 0.999 | D | 0.629 | neutral | None | None | None | None | N |
| T/F | 0.7146 | likely_pathogenic | 0.6933 | pathogenic | -0.678 | Destabilizing | 0.995 | D | 0.687 | prob.neutral | None | None | None | None | N |
| T/G | 0.7717 | likely_pathogenic | 0.7541 | pathogenic | -0.473 | Destabilizing | 0.999 | D | 0.586 | neutral | None | None | None | None | N |
| T/H | 0.5674 | likely_pathogenic | 0.5356 | ambiguous | -0.713 | Destabilizing | 1.0 | D | 0.65 | neutral | None | None | None | None | N |
| T/I | 0.5121 | ambiguous | 0.4859 | ambiguous | 0.022 | Stabilizing | 0.235 | N | 0.251 | neutral | N | 0.505611362 | None | None | N |
| T/K | 0.4784 | ambiguous | 0.4475 | ambiguous | -0.432 | Destabilizing | 0.998 | D | 0.628 | neutral | None | None | None | None | N |
| T/L | 0.3074 | likely_benign | 0.2945 | benign | 0.022 | Stabilizing | 0.966 | D | 0.445 | neutral | None | None | None | None | N |
| T/M | 0.1692 | likely_benign | 0.1608 | benign | -0.022 | Destabilizing | 0.999 | D | 0.602 | neutral | None | None | None | None | N |
| T/N | 0.305 | likely_benign | 0.283 | benign | -0.331 | Destabilizing | 0.999 | D | 0.611 | neutral | N | 0.487136109 | None | None | N |
| T/P | 0.6571 | likely_pathogenic | 0.6496 | pathogenic | -0.056 | Destabilizing | 0.999 | D | 0.615 | neutral | N | 0.510474712 | None | None | N |
| T/Q | 0.5163 | ambiguous | 0.4844 | ambiguous | -0.484 | Destabilizing | 0.999 | D | 0.631 | neutral | None | None | None | None | N |
| T/R | 0.4149 | ambiguous | 0.3878 | ambiguous | -0.183 | Destabilizing | 0.999 | D | 0.621 | neutral | None | None | None | None | N |
| T/S | 0.2897 | likely_benign | 0.2695 | benign | -0.53 | Destabilizing | 0.989 | D | 0.453 | neutral | N | 0.486456362 | None | None | N |
| T/V | 0.3679 | ambiguous | 0.3454 | ambiguous | -0.056 | Destabilizing | 0.921 | D | 0.427 | neutral | None | None | None | None | N |
| T/W | 0.9077 | likely_pathogenic | 0.8996 | pathogenic | -0.711 | Destabilizing | 1.0 | D | 0.704 | prob.neutral | None | None | None | None | N |
| T/Y | 0.7359 | likely_pathogenic | 0.7135 | pathogenic | -0.416 | Destabilizing | 0.999 | D | 0.69 | prob.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.