Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35218 | 105877;105878;105879 | chr2:178530963;178530962;178530961 | chr2:179395690;179395689;179395688 |
| N2AB | 33577 | 100954;100955;100956 | chr2:178530963;178530962;178530961 | chr2:179395690;179395689;179395688 |
| N2A | 32650 | 98173;98174;98175 | chr2:178530963;178530962;178530961 | chr2:179395690;179395689;179395688 |
| N2B | 26153 | 78682;78683;78684 | chr2:178530963;178530962;178530961 | chr2:179395690;179395689;179395688 |
| Novex-1 | 26278 | 79057;79058;79059 | chr2:178530963;178530962;178530961 | chr2:179395690;179395689;179395688 |
| Novex-2 | 26345 | 79258;79259;79260 | chr2:178530963;178530962;178530961 | chr2:179395690;179395689;179395688 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/L | None | None | None | D | 0.249 | 0.138 | 0.151104730317 | gnomAD-4.0.0 | 1.59088E-06 | None | None | None | None | N | None | 0 | 0 | None | 4.76554E-05 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs143499441  |
-2.21 | None | N | 0.336 | 0.357 | None | gnomAD-2.1.1 | 2.16939E-04 | None | None | None | None | N | None | 0 | 0 | None | 0 | 3.00434E-03 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs143499441 |
-2.21 | None | N | 0.336 | 0.357 | None | gnomAD-3.1.2 | 7.23E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 2.12028E-03 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs143499441 |
-2.21 | None | N | 0.336 | 0.357 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 2E-03 | 0 | None | None | None | 0 | None |
| I/T | rs143499441 |
-2.21 | None | N | 0.336 | 0.357 | None | gnomAD-4.0.0 | 1.75975E-04 | None | None | None | None | N | None | 0 | 0 | None | 0 | 6.30627E-03 | None | 0 | 0 | 0 | 0 | 1.60031E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.6549 | likely_pathogenic | 0.7217 | pathogenic | -2.246 | Highly Destabilizing | 0.003 | N | 0.531 | neutral | None | None | None | None | N |
| I/C | 0.8688 | likely_pathogenic | 0.9016 | pathogenic | -1.622 | Destabilizing | 0.177 | N | 0.639 | neutral | None | None | None | None | N |
| I/D | 0.9714 | likely_pathogenic | 0.9876 | pathogenic | -2.348 | Highly Destabilizing | 0.096 | N | 0.68 | prob.neutral | None | None | None | None | N |
| I/E | 0.9427 | likely_pathogenic | 0.9656 | pathogenic | -2.284 | Highly Destabilizing | 0.029 | N | 0.65 | neutral | None | None | None | None | N |
| I/F | 0.4386 | ambiguous | 0.6005 | pathogenic | -1.554 | Destabilizing | 0.011 | N | 0.501 | neutral | N | 0.508176174 | None | None | N |
| I/G | 0.8924 | likely_pathogenic | 0.9358 | pathogenic | -2.628 | Highly Destabilizing | 0.029 | N | 0.633 | neutral | None | None | None | None | N |
| I/H | 0.9313 | likely_pathogenic | 0.9646 | pathogenic | -1.865 | Destabilizing | 0.712 | D | 0.707 | prob.neutral | None | None | None | None | N |
| I/K | 0.8829 | likely_pathogenic | 0.9289 | pathogenic | -1.629 | Destabilizing | 0.029 | N | 0.649 | neutral | None | None | None | None | N |
| I/L | 0.2508 | likely_benign | 0.3078 | benign | -1.214 | Destabilizing | None | N | 0.249 | neutral | D | 0.538046863 | None | None | N |
| I/M | 0.2907 | likely_benign | 0.3775 | ambiguous | -1.089 | Destabilizing | 0.074 | N | 0.541 | neutral | N | 0.519785969 | None | None | N |
| I/N | 0.7929 | likely_pathogenic | 0.8699 | pathogenic | -1.615 | Destabilizing | 0.074 | N | 0.685 | prob.neutral | N | 0.520292948 | None | None | N |
| I/P | 0.9169 | likely_pathogenic | 0.9502 | pathogenic | -1.532 | Destabilizing | 0.177 | N | 0.683 | prob.neutral | None | None | None | None | N |
| I/Q | 0.902 | likely_pathogenic | 0.9405 | pathogenic | -1.768 | Destabilizing | 0.177 | N | 0.705 | prob.neutral | None | None | None | None | N |
| I/R | 0.8203 | likely_pathogenic | 0.8786 | pathogenic | -1.055 | Destabilizing | 0.096 | N | 0.685 | prob.neutral | None | None | None | None | N |
| I/S | 0.713 | likely_pathogenic | 0.7932 | pathogenic | -2.23 | Highly Destabilizing | 0.011 | N | 0.543 | neutral | N | 0.520039459 | None | None | N |
| I/T | 0.5996 | likely_pathogenic | 0.6771 | pathogenic | -2.052 | Highly Destabilizing | None | N | 0.336 | neutral | N | 0.501846298 | None | None | N |
| I/V | 0.0696 | likely_benign | 0.0639 | benign | -1.532 | Destabilizing | None | N | 0.243 | neutral | N | 0.370352863 | None | None | N |
| I/W | 0.9565 | likely_pathogenic | 0.9825 | pathogenic | -1.716 | Destabilizing | 0.712 | D | 0.701 | prob.neutral | None | None | None | None | N |
| I/Y | 0.8604 | likely_pathogenic | 0.9261 | pathogenic | -1.489 | Destabilizing | 0.177 | N | 0.605 | 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.