Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17496 | 52711;52712;52713 | chr2:178608397;178608396;178608395 | chr2:179473124;179473123;179473122 |
| N2AB | 15855 | 47788;47789;47790 | chr2:178608397;178608396;178608395 | chr2:179473124;179473123;179473122 |
| N2A | 14928 | 45007;45008;45009 | chr2:178608397;178608396;178608395 | chr2:179473124;179473123;179473122 |
| N2B | 8431 | 25516;25517;25518 | chr2:178608397;178608396;178608395 | chr2:179473124;179473123;179473122 |
| Novex-1 | 8556 | 25891;25892;25893 | chr2:178608397;178608396;178608395 | chr2:179473124;179473123;179473122 |
| Novex-2 | 8623 | 26092;26093;26094 | chr2:178608397;178608396;178608395 | chr2:179473124;179473123;179473122 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs1227243648  |
None | 0.999 | N | 0.462 | 0.318 | 0.244539031024 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/E | rs1227243648 |
None | 0.999 | N | 0.462 | 0.318 | 0.244539031024 | gnomAD-4.0.0 | 3.85855E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.20423E-06 | 0 | 0 |
| D/H | None | None | 1.0 | N | 0.671 | 0.471 | 0.370051654043 | gnomAD-4.0.0 | 3.19873E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.74089E-06 | 0 | 0 |
| D/V | rs1224355854 |
0.206 | 1.0 | N | 0.665 | 0.477 | 0.650134695354 | gnomAD-2.1.1 | 7.3E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.6E-05 | 0 |
| D/V | rs1224355854 |
0.206 | 1.0 | N | 0.665 | 0.477 | 0.650134695354 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 9.41E-05 | 0 | 2.94E-05 | 0 | 0 |
| D/V | rs1224355854 |
0.206 | 1.0 | N | 0.665 | 0.477 | 0.650134695354 | gnomAD-4.0.0 | 6.43218E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 1.57361E-05 | 0 | 9.60693E-06 | 0 | 0 |
| D/Y | rs2055441227 |
None | 1.0 | N | 0.659 | 0.525 | 0.729283302134 | gnomAD-4.0.0 | 1.59937E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.87045E-06 | 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 | 0.7615 | likely_pathogenic | 0.7841 | pathogenic | -0.198 | Destabilizing | 0.996 | D | 0.61 | neutral | N | 0.491905803 | None | None | I |
| D/C | 0.9579 | likely_pathogenic | 0.9653 | pathogenic | -0.002 | Destabilizing | 1.0 | D | 0.662 | neutral | None | None | None | None | I |
| D/E | 0.7532 | likely_pathogenic | 0.7791 | pathogenic | -0.709 | Destabilizing | 0.999 | D | 0.462 | neutral | N | 0.494018943 | None | None | I |
| D/F | 0.9603 | likely_pathogenic | 0.9737 | pathogenic | -0.283 | Destabilizing | 1.0 | D | 0.665 | neutral | None | None | None | None | I |
| D/G | 0.547 | ambiguous | 0.5815 | pathogenic | -0.498 | Destabilizing | 0.434 | N | 0.36 | neutral | N | 0.508074728 | None | None | I |
| D/H | 0.8724 | likely_pathogenic | 0.8901 | pathogenic | -0.755 | Destabilizing | 1.0 | D | 0.671 | neutral | N | 0.498426716 | None | None | I |
| D/I | 0.9426 | likely_pathogenic | 0.9491 | pathogenic | 0.565 | Stabilizing | 1.0 | D | 0.673 | neutral | None | None | None | None | I |
| D/K | 0.9012 | likely_pathogenic | 0.9318 | pathogenic | -0.302 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | I |
| D/L | 0.923 | likely_pathogenic | 0.9408 | pathogenic | 0.565 | Stabilizing | 1.0 | D | 0.661 | neutral | None | None | None | None | I |
| D/M | 0.9673 | likely_pathogenic | 0.9732 | pathogenic | 0.982 | Stabilizing | 1.0 | D | 0.649 | neutral | None | None | None | None | I |
| D/N | 0.296 | likely_benign | 0.2649 | benign | -0.539 | Destabilizing | 0.999 | D | 0.722 | prob.delet. | N | 0.472244612 | None | None | I |
| D/P | 0.939 | likely_pathogenic | 0.9494 | pathogenic | 0.337 | Stabilizing | 1.0 | D | 0.724 | prob.delet. | None | None | None | None | I |
| D/Q | 0.8947 | likely_pathogenic | 0.9224 | pathogenic | -0.423 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | I |
| D/R | 0.9207 | likely_pathogenic | 0.9459 | pathogenic | -0.32 | Destabilizing | 1.0 | D | 0.7 | prob.neutral | None | None | None | None | I |
| D/S | 0.5317 | ambiguous | 0.5211 | ambiguous | -0.729 | Destabilizing | 0.997 | D | 0.636 | neutral | None | None | None | None | I |
| D/T | 0.7425 | likely_pathogenic | 0.7503 | pathogenic | -0.498 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | I |
| D/V | 0.8544 | likely_pathogenic | 0.8701 | pathogenic | 0.337 | Stabilizing | 1.0 | D | 0.665 | neutral | N | 0.502528093 | None | None | I |
| D/W | 0.9894 | likely_pathogenic | 0.9926 | pathogenic | -0.317 | Destabilizing | 1.0 | D | 0.678 | prob.neutral | None | None | None | None | I |
| D/Y | 0.7568 | likely_pathogenic | 0.8029 | pathogenic | -0.113 | Destabilizing | 1.0 | D | 0.659 | neutral | N | 0.51729144 | None | None | I |
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.