Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22144 | 66655;66656;66657 | chr2:178581939;178581938;178581937 | chr2:179446666;179446665;179446664 |
| N2AB | 20503 | 61732;61733;61734 | chr2:178581939;178581938;178581937 | chr2:179446666;179446665;179446664 |
| N2A | 19576 | 58951;58952;58953 | chr2:178581939;178581938;178581937 | chr2:179446666;179446665;179446664 |
| N2B | 13079 | 39460;39461;39462 | chr2:178581939;178581938;178581937 | chr2:179446666;179446665;179446664 |
| Novex-1 | 13204 | 39835;39836;39837 | chr2:178581939;178581938;178581937 | chr2:179446666;179446665;179446664 |
| Novex-2 | 13271 | 40036;40037;40038 | chr2:178581939;178581938;178581937 | chr2:179446666;179446665;179446664 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/T | rs183276016  |
-0.606 | 0.614 | N | 0.514 | 0.137 | None | gnomAD-2.1.1 | 2.71673E-04 | None | None | None | None | N | None | 3.72147E-04 | 5.66669E-04 | None | 0 | 0 | None | 0 | None | 0 | 3.5974E-04 | 1.40568E-04 |
| A/T | rs183276016 |
-0.606 | 0.614 | N | 0.514 | 0.137 | None | gnomAD-3.1.2 | 2.49878E-04 | None | None | None | None | N | None | 2.17223E-04 | 5.23834E-04 | 0 | 0 | 0 | None | 0 | 0 | 2.79461E-04 | 0 | 9.56938E-04 |
| A/T | rs183276016 |
-0.606 | 0.614 | N | 0.514 | 0.137 | None | gnomAD-4.0.0 | 4.64334E-04 | None | None | None | None | N | None | 2.13738E-04 | 5.33707E-04 | None | 0 | 4.47207E-05 | None | 0 | 0 | 5.7229E-04 | 1.09796E-05 | 3.68483E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.4421 | ambiguous | 0.4496 | ambiguous | -0.954 | Destabilizing | 0.953 | D | 0.536 | neutral | None | None | None | None | N |
| A/D | 0.5966 | likely_pathogenic | 0.6196 | pathogenic | -1.282 | Destabilizing | 0.724 | D | 0.669 | prob.neutral | None | None | None | None | N |
| A/E | 0.4524 | ambiguous | 0.478 | ambiguous | -1.339 | Destabilizing | 0.361 | N | 0.605 | neutral | N | 0.454541966 | None | None | N |
| A/F | 0.495 | ambiguous | 0.5001 | ambiguous | -1.228 | Destabilizing | 0.724 | D | 0.703 | prob.delet. | None | None | None | None | N |
| A/G | 0.2048 | likely_benign | 0.2101 | benign | -1.285 | Destabilizing | 0.22 | N | 0.487 | neutral | N | 0.47069354 | None | None | N |
| A/H | 0.6429 | likely_pathogenic | 0.6672 | pathogenic | -1.344 | Destabilizing | 0.984 | D | 0.665 | prob.neutral | None | None | None | None | N |
| A/I | 0.2252 | likely_benign | 0.224 | benign | -0.61 | Destabilizing | 0.114 | N | 0.604 | neutral | None | None | None | None | N |
| A/K | 0.6369 | likely_pathogenic | 0.6645 | pathogenic | -1.193 | Destabilizing | 0.428 | N | 0.604 | neutral | None | None | None | None | N |
| A/L | 0.2367 | likely_benign | 0.2503 | benign | -0.61 | Destabilizing | 0.272 | N | 0.561 | neutral | None | None | None | None | N |
| A/M | 0.318 | likely_benign | 0.322 | benign | -0.46 | Destabilizing | 0.724 | D | 0.589 | neutral | None | None | None | None | N |
| A/N | 0.4156 | ambiguous | 0.4182 | ambiguous | -0.867 | Destabilizing | 0.724 | D | 0.689 | prob.delet. | None | None | None | None | N |
| A/P | 0.0855 | likely_benign | 0.0901 | benign | -0.722 | Destabilizing | 0.002 | N | 0.309 | neutral | N | 0.365632116 | None | None | N |
| A/Q | 0.4853 | ambiguous | 0.5254 | ambiguous | -1.1 | Destabilizing | 0.842 | D | 0.623 | neutral | None | None | None | None | N |
| A/R | 0.5871 | likely_pathogenic | 0.6269 | pathogenic | -0.774 | Destabilizing | 0.724 | D | 0.627 | neutral | None | None | None | None | N |
| A/S | 0.1227 | likely_benign | 0.1187 | benign | -1.208 | Destabilizing | 0.019 | N | 0.364 | neutral | N | 0.455984761 | None | None | N |
| A/T | 0.1094 | likely_benign | 0.1079 | benign | -1.182 | Destabilizing | 0.614 | D | 0.514 | neutral | N | 0.45419525 | None | None | N |
| A/V | 0.1313 | likely_benign | 0.1344 | benign | -0.722 | Destabilizing | 0.002 | N | 0.383 | neutral | N | 0.444959691 | None | None | N |
| A/W | 0.8633 | likely_pathogenic | 0.878 | pathogenic | -1.479 | Destabilizing | 0.984 | D | 0.779 | deleterious | None | None | None | None | N |
| A/Y | 0.635 | likely_pathogenic | 0.6453 | pathogenic | -1.123 | Destabilizing | 0.842 | D | 0.691 | prob.delet. | 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.