Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2489 | 7690;7691;7692 | chr2:178773591;178773590;178773589 | chr2:179638318;179638317;179638316 |
| N2AB | 2489 | 7690;7691;7692 | chr2:178773591;178773590;178773589 | chr2:179638318;179638317;179638316 |
| N2A | 2489 | 7690;7691;7692 | chr2:178773591;178773590;178773589 | chr2:179638318;179638317;179638316 |
| N2B | 2443 | 7552;7553;7554 | chr2:178773591;178773590;178773589 | chr2:179638318;179638317;179638316 |
| Novex-1 | 2443 | 7552;7553;7554 | chr2:178773591;178773590;178773589 | chr2:179638318;179638317;179638316 |
| Novex-2 | 2443 | 7552;7553;7554 | chr2:178773591;178773590;178773589 | chr2:179638318;179638317;179638316 |
| Novex-3 | 2489 | 7690;7691;7692 | chr2:178773591;178773590;178773589 | chr2:179638318;179638317;179638316 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs2091842638  |
None | 0.046 | N | 0.307 | 0.083 | 0.146414634003 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.78469E-04 |
| D/E | rs2091842638 |
None | 0.046 | N | 0.307 | 0.083 | 0.146414634003 | gnomAD-4.0.0 | 3.84234E-06 | None | None | None | None | N | None | 0 | 1.69497E-05 | None | 0 | 0 | None | 0 | 0 | 2.39198E-06 | 0 | 2.84236E-05 |
| D/N | None | None | 0.982 | N | 0.422 | 0.255 | 0.348983352498 | gnomAD-4.0.0 | 6.84111E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99318E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.176 | likely_benign | 0.1844 | benign | 0.033 | Stabilizing | 0.939 | D | 0.426 | neutral | N | 0.445897683 | None | None | N |
| D/C | 0.6122 | likely_pathogenic | 0.638 | pathogenic | 0.074 | Stabilizing | 0.999 | D | 0.609 | neutral | None | None | None | None | N |
| D/E | 0.1197 | likely_benign | 0.1178 | benign | -0.152 | Destabilizing | 0.046 | N | 0.307 | neutral | N | 0.435870801 | None | None | N |
| D/F | 0.6141 | likely_pathogenic | 0.6361 | pathogenic | -0.15 | Destabilizing | 0.986 | D | 0.568 | neutral | None | None | None | None | N |
| D/G | 0.1594 | likely_benign | 0.1714 | benign | -0.076 | Destabilizing | 0.939 | D | 0.381 | neutral | N | 0.445600768 | None | None | N |
| D/H | 0.2981 | likely_benign | 0.3161 | benign | 0.32 | Stabilizing | 0.998 | D | 0.437 | neutral | N | 0.435646263 | None | None | N |
| D/I | 0.371 | ambiguous | 0.3906 | ambiguous | 0.249 | Stabilizing | 0.973 | D | 0.573 | neutral | None | None | None | None | N |
| D/K | 0.3028 | likely_benign | 0.3238 | benign | 0.476 | Stabilizing | 0.91 | D | 0.403 | neutral | None | None | None | None | N |
| D/L | 0.4072 | ambiguous | 0.4244 | ambiguous | 0.249 | Stabilizing | 0.128 | N | 0.483 | neutral | None | None | None | None | N |
| D/M | 0.5973 | likely_pathogenic | 0.6068 | pathogenic | 0.17 | Stabilizing | 0.996 | D | 0.555 | neutral | None | None | None | None | N |
| D/N | 0.1007 | likely_benign | 0.104 | benign | 0.406 | Stabilizing | 0.982 | D | 0.422 | neutral | N | 0.440893073 | None | None | N |
| D/P | 0.6492 | likely_pathogenic | 0.6514 | pathogenic | 0.196 | Stabilizing | 0.993 | D | 0.433 | neutral | None | None | None | None | N |
| D/Q | 0.3125 | likely_benign | 0.3227 | benign | 0.387 | Stabilizing | 0.973 | D | 0.457 | neutral | None | None | None | None | N |
| D/R | 0.3835 | ambiguous | 0.4117 | ambiguous | 0.627 | Stabilizing | 0.986 | D | 0.493 | neutral | None | None | None | None | N |
| D/S | 0.1148 | likely_benign | 0.1182 | benign | 0.263 | Stabilizing | 0.953 | D | 0.398 | neutral | None | None | None | None | N |
| D/T | 0.25 | likely_benign | 0.2582 | benign | 0.345 | Stabilizing | 0.986 | D | 0.385 | neutral | None | None | None | None | N |
| D/V | 0.2325 | likely_benign | 0.2469 | benign | 0.196 | Stabilizing | 0.964 | D | 0.503 | neutral | N | 0.481245093 | None | None | N |
| D/W | 0.8914 | likely_pathogenic | 0.9026 | pathogenic | -0.137 | Destabilizing | 0.999 | D | 0.633 | neutral | None | None | None | None | N |
| D/Y | 0.2727 | likely_benign | 0.3 | benign | 0.068 | Stabilizing | 0.997 | D | 0.563 | neutral | D | 0.544917125 | 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.