Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32367 | 97324;97325;97326 | chr2:178542755;178542754;178542753 | chr2:179407482;179407481;179407480 |
| N2AB | 30726 | 92401;92402;92403 | chr2:178542755;178542754;178542753 | chr2:179407482;179407481;179407480 |
| N2A | 29799 | 89620;89621;89622 | chr2:178542755;178542754;178542753 | chr2:179407482;179407481;179407480 |
| N2B | 23302 | 70129;70130;70131 | chr2:178542755;178542754;178542753 | chr2:179407482;179407481;179407480 |
| Novex-1 | 23427 | 70504;70505;70506 | chr2:178542755;178542754;178542753 | chr2:179407482;179407481;179407480 |
| Novex-2 | 23494 | 70705;70706;70707 | chr2:178542755;178542754;178542753 | chr2:179407482;179407481;179407480 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs202064385  |
-0.916 | 1.0 | N | 0.657 | 0.476 | None | gnomAD-2.1.1 | 4.10723E-04 | None | None | None | None | N | None | 0 | 3.39309E-04 | None | 9.67305E-04 | 7.17213E-04 | None | 1.56853E-03 | None | 0 | 2.03347E-04 | 7.02247E-04 |
| R/C | rs202064385 |
-0.916 | 1.0 | N | 0.657 | 0.476 | None | gnomAD-3.1.2 | 3.5509E-04 | None | None | None | None | N | None | 0 | 9.82061E-04 | 0 | 2.88184E-03 | 7.73096E-04 | None | 0 | 0 | 2.20549E-04 | 1.86335E-03 | 4.79846E-04 |
| R/C | rs202064385 |
-0.916 | 1.0 | N | 0.657 | 0.476 | None | gnomAD-4.0.0 | 3.01787E-04 | None | None | None | None | N | None | 6.66613E-05 | 4.83221E-04 | None | 1.79042E-03 | 8.47155E-04 | None | 0 | 1.32013E-03 | 1.22907E-04 | 1.99833E-03 | 4.32207E-04 |
| R/H | rs777181557 |
-1.501 | 1.0 | N | 0.653 | 0.407 | None | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.35E-05 | 0 |
| R/H | rs777181557 |
-1.501 | 1.0 | N | 0.653 | 0.407 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/H | rs777181557 |
-1.501 | 1.0 | N | 0.653 | 0.407 | None | gnomAD-4.0.0 | 1.48732E-05 | None | None | None | None | N | None | 2.67073E-05 | 0 | None | 3.37815E-05 | 0 | None | 0 | 0 | 1.78E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.463 | ambiguous | 0.3912 | ambiguous | -0.866 | Destabilizing | 0.999 | D | 0.595 | neutral | None | None | None | None | N |
| R/C | 0.2324 | likely_benign | 0.1834 | benign | -0.835 | Destabilizing | 1.0 | D | 0.657 | neutral | N | 0.507813191 | None | None | N |
| R/D | 0.7474 | likely_pathogenic | 0.6966 | pathogenic | -0.113 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| R/E | 0.4628 | ambiguous | 0.4098 | ambiguous | 0.016 | Stabilizing | 0.999 | D | 0.615 | neutral | None | None | None | None | N |
| R/F | 0.6547 | likely_pathogenic | 0.601 | pathogenic | -0.625 | Destabilizing | 1.0 | D | 0.67 | neutral | None | None | None | None | N |
| R/G | 0.2996 | likely_benign | 0.2434 | benign | -1.19 | Destabilizing | 1.0 | D | 0.637 | neutral | N | 0.488948467 | None | None | N |
| R/H | 0.1288 | likely_benign | 0.1097 | benign | -1.386 | Destabilizing | 1.0 | D | 0.653 | neutral | N | 0.485575028 | None | None | N |
| R/I | 0.4116 | ambiguous | 0.3649 | ambiguous | 0.008 | Stabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| R/K | 0.1154 | likely_benign | 0.1063 | benign | -0.96 | Destabilizing | 0.998 | D | 0.485 | neutral | None | None | None | None | N |
| R/L | 0.3175 | likely_benign | 0.2693 | benign | 0.008 | Stabilizing | 1.0 | D | 0.637 | neutral | N | 0.502024561 | None | None | N |
| R/M | 0.3864 | ambiguous | 0.3338 | benign | -0.32 | Destabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | N |
| R/N | 0.6352 | likely_pathogenic | 0.5718 | pathogenic | -0.393 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | N |
| R/P | 0.6672 | likely_pathogenic | 0.6381 | pathogenic | -0.263 | Destabilizing | 1.0 | D | 0.664 | neutral | N | 0.516108579 | None | None | N |
| R/Q | 0.1178 | likely_benign | 0.103 | benign | -0.55 | Destabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | N |
| R/S | 0.5453 | ambiguous | 0.4847 | ambiguous | -1.182 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | N | 0.480089064 | None | None | N |
| R/T | 0.3014 | likely_benign | 0.2562 | benign | -0.869 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | N |
| R/V | 0.4611 | ambiguous | 0.4068 | ambiguous | -0.263 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| R/W | 0.2259 | likely_benign | 0.1913 | benign | -0.239 | Destabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | N |
| R/Y | 0.5071 | ambiguous | 0.4368 | ambiguous | 0.033 | Stabilizing | 1.0 | D | 0.673 | 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.