Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1091 | 3496;3497;3498 | chr2:178782321;178782320;178782319 | chr2:179647048;179647047;179647046 |
| N2AB | 1091 | 3496;3497;3498 | chr2:178782321;178782320;178782319 | chr2:179647048;179647047;179647046 |
| N2A | 1091 | 3496;3497;3498 | chr2:178782321;178782320;178782319 | chr2:179647048;179647047;179647046 |
| N2B | 1045 | 3358;3359;3360 | chr2:178782321;178782320;178782319 | chr2:179647048;179647047;179647046 |
| Novex-1 | 1045 | 3358;3359;3360 | chr2:178782321;178782320;178782319 | chr2:179647048;179647047;179647046 |
| Novex-2 | 1045 | 3358;3359;3360 | chr2:178782321;178782320;178782319 | chr2:179647048;179647047;179647046 |
| Novex-3 | 1091 | 3496;3497;3498 | chr2:178782321;178782320;178782319 | chr2:179647048;179647047;179647046 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Q/E | rs794729528  |
None | 0.78 | N | 0.471 | 0.315 | 0.260249123532 | gnomAD-4.0.0 | 2.05222E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.6979E-06 | 0 | 0 |
| Q/R | rs779873815 |
-0.133 | 0.896 | N | 0.486 | 0.392 | 0.21279746466 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.81E-06 | 0 |
| Q/R | rs779873815 |
-0.133 | 0.896 | N | 0.486 | 0.392 | 0.21279746466 | gnomAD-4.0.0 | 1.59052E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85652E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Q/A | 0.5771 | likely_pathogenic | 0.5709 | pathogenic | -0.561 | Destabilizing | 0.919 | D | 0.459 | neutral | None | None | None | None | I |
| Q/C | 0.9015 | likely_pathogenic | 0.894 | pathogenic | 0.026 | Stabilizing | 0.999 | D | 0.659 | neutral | None | None | None | None | I |
| Q/D | 0.8952 | likely_pathogenic | 0.8941 | pathogenic | -0.347 | Destabilizing | 0.919 | D | 0.471 | neutral | None | None | None | None | I |
| Q/E | 0.1616 | likely_benign | 0.1608 | benign | -0.164 | Destabilizing | 0.78 | D | 0.471 | neutral | N | 0.502717519 | None | None | I |
| Q/F | 0.9506 | likely_pathogenic | 0.9463 | pathogenic | -0.076 | Destabilizing | 0.988 | D | 0.659 | neutral | None | None | None | None | I |
| Q/G | 0.6806 | likely_pathogenic | 0.6732 | pathogenic | -0.972 | Destabilizing | 0.919 | D | 0.527 | neutral | None | None | None | None | I |
| Q/H | 0.6066 | likely_pathogenic | 0.5955 | pathogenic | -0.563 | Destabilizing | 0.059 | N | 0.276 | neutral | N | 0.486933042 | None | None | I |
| Q/I | 0.8225 | likely_pathogenic | 0.8231 | pathogenic | 0.522 | Stabilizing | 0.988 | D | 0.649 | neutral | None | None | None | None | I |
| Q/K | 0.2376 | likely_benign | 0.2454 | benign | -0.07 | Destabilizing | 0.896 | D | 0.458 | neutral | N | 0.483752512 | None | None | I |
| Q/L | 0.406 | ambiguous | 0.3933 | ambiguous | 0.522 | Stabilizing | 0.896 | D | 0.514 | neutral | N | 0.436381534 | None | None | I |
| Q/M | 0.6405 | likely_pathogenic | 0.6277 | pathogenic | 0.658 | Stabilizing | 0.996 | D | 0.463 | neutral | None | None | None | None | I |
| Q/N | 0.7272 | likely_pathogenic | 0.7168 | pathogenic | -0.759 | Destabilizing | 0.919 | D | 0.475 | neutral | None | None | None | None | I |
| Q/P | 0.9442 | likely_pathogenic | 0.9392 | pathogenic | 0.192 | Stabilizing | 0.995 | D | 0.505 | neutral | D | 0.540958484 | None | None | I |
| Q/R | 0.2605 | likely_benign | 0.2656 | benign | -0.16 | Destabilizing | 0.896 | D | 0.486 | neutral | N | 0.480166955 | None | None | I |
| Q/S | 0.6581 | likely_pathogenic | 0.6512 | pathogenic | -0.966 | Destabilizing | 0.919 | D | 0.441 | neutral | None | None | None | None | I |
| Q/T | 0.5856 | likely_pathogenic | 0.5823 | pathogenic | -0.573 | Destabilizing | 0.959 | D | 0.477 | neutral | None | None | None | None | I |
| Q/V | 0.6255 | likely_pathogenic | 0.6187 | pathogenic | 0.192 | Stabilizing | 0.988 | D | 0.507 | neutral | None | None | None | None | I |
| Q/W | 0.925 | likely_pathogenic | 0.9174 | pathogenic | 0.007 | Stabilizing | 0.999 | D | 0.615 | neutral | None | None | None | None | I |
| Q/Y | 0.8754 | likely_pathogenic | 0.8696 | pathogenic | 0.304 | Stabilizing | 0.976 | D | 0.501 | neutral | None | None | None | None | I |
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.