Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35169 | 105730;105731;105732 | chr2:178531110;178531109;178531108 | chr2:179395837;179395836;179395835 |
| N2AB | 33528 | 100807;100808;100809 | chr2:178531110;178531109;178531108 | chr2:179395837;179395836;179395835 |
| N2A | 32601 | 98026;98027;98028 | chr2:178531110;178531109;178531108 | chr2:179395837;179395836;179395835 |
| N2B | 26104 | 78535;78536;78537 | chr2:178531110;178531109;178531108 | chr2:179395837;179395836;179395835 |
| Novex-1 | 26229 | 78910;78911;78912 | chr2:178531110;178531109;178531108 | chr2:179395837;179395836;179395835 |
| Novex-2 | 26296 | 79111;79112;79113 | chr2:178531110;178531109;178531108 | chr2:179395837;179395836;179395835 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/P | None | None | 0.14 | N | 0.577 | 0.62 | 0.814514831683 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| L/V | None | None | None | N | 0.111 | 0.084 | 0.246773566709 | gnomAD-4.0.0 | 1.36827E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.31863E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.483 | ambiguous | 0.4226 | ambiguous | -2.213 | Highly Destabilizing | 0.006 | N | 0.386 | neutral | None | None | None | None | N |
| L/C | 0.6055 | likely_pathogenic | 0.5615 | ambiguous | -1.378 | Destabilizing | 0.177 | N | 0.528 | neutral | None | None | None | None | N |
| L/D | 0.9137 | likely_pathogenic | 0.8706 | pathogenic | -1.897 | Destabilizing | 0.177 | N | 0.577 | neutral | None | None | None | None | N |
| L/E | 0.7162 | likely_pathogenic | 0.6552 | pathogenic | -1.703 | Destabilizing | 0.058 | N | 0.548 | neutral | None | None | None | None | N |
| L/F | 0.1909 | likely_benign | 0.1674 | benign | -1.317 | Destabilizing | 0.029 | N | 0.463 | neutral | None | None | None | None | N |
| L/G | 0.8007 | likely_pathogenic | 0.7346 | pathogenic | -2.703 | Highly Destabilizing | 0.058 | N | 0.539 | neutral | None | None | None | None | N |
| L/H | 0.4666 | ambiguous | 0.403 | ambiguous | -1.875 | Destabilizing | 0.712 | D | 0.554 | neutral | None | None | None | None | N |
| L/I | 0.0562 | likely_benign | 0.0577 | benign | -0.823 | Destabilizing | None | N | 0.1 | neutral | N | 0.450483807 | None | None | N |
| L/K | 0.6376 | likely_pathogenic | 0.5419 | ambiguous | -1.49 | Destabilizing | 0.029 | N | 0.513 | neutral | None | None | None | None | N |
| L/M | 0.1413 | likely_benign | 0.1364 | benign | -0.747 | Destabilizing | 0.001 | N | 0.173 | neutral | None | None | None | None | N |
| L/N | 0.6832 | likely_pathogenic | 0.594 | pathogenic | -1.687 | Destabilizing | 0.177 | N | 0.563 | neutral | None | None | None | None | N |
| L/P | 0.6702 | likely_pathogenic | 0.5346 | ambiguous | -1.265 | Destabilizing | 0.14 | N | 0.577 | neutral | N | 0.520635343 | None | None | N |
| L/Q | 0.4354 | ambiguous | 0.3727 | ambiguous | -1.59 | Destabilizing | 0.14 | N | 0.53 | neutral | D | 0.550349393 | None | None | N |
| L/R | 0.4865 | ambiguous | 0.3942 | ambiguous | -1.233 | Destabilizing | 0.074 | N | 0.552 | neutral | D | 0.550095904 | None | None | N |
| L/S | 0.6289 | likely_pathogenic | 0.5487 | ambiguous | -2.419 | Highly Destabilizing | 0.029 | N | 0.485 | neutral | None | None | None | None | N |
| L/T | 0.4476 | ambiguous | 0.3824 | ambiguous | -2.07 | Highly Destabilizing | 0.006 | N | 0.437 | neutral | None | None | None | None | N |
| L/V | 0.0833 | likely_benign | 0.0849 | benign | -1.265 | Destabilizing | None | N | 0.111 | neutral | N | 0.46910964 | None | None | N |
| L/W | 0.4263 | ambiguous | 0.365 | ambiguous | -1.509 | Destabilizing | 0.712 | D | 0.537 | neutral | None | None | None | None | N |
| L/Y | 0.5097 | ambiguous | 0.4558 | ambiguous | -1.241 | Destabilizing | 0.177 | N | 0.545 | 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.