Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24431 | 73516;73517;73518 | chr2:178572841;178572840;178572839 | chr2:179437568;179437567;179437566 |
| N2AB | 22790 | 68593;68594;68595 | chr2:178572841;178572840;178572839 | chr2:179437568;179437567;179437566 |
| N2A | 21863 | 65812;65813;65814 | chr2:178572841;178572840;178572839 | chr2:179437568;179437567;179437566 |
| N2B | 15366 | 46321;46322;46323 | chr2:178572841;178572840;178572839 | chr2:179437568;179437567;179437566 |
| Novex-1 | 15491 | 46696;46697;46698 | chr2:178572841;178572840;178572839 | chr2:179437568;179437567;179437566 |
| Novex-2 | 15558 | 46897;46898;46899 | chr2:178572841;178572840;178572839 | chr2:179437568;179437567;179437566 |
| 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/N | rs757317072  |
0.264 | 0.999 | N | 0.639 | 0.43 | 0.408036853922 | gnomAD-2.1.1 | 3.63E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.04145E-04 | None | 0 | None | 0 | 0 | 0 |
| D/N | rs757317072 |
0.264 | 0.999 | N | 0.639 | 0.43 | 0.408036853922 | gnomAD-4.0.0 | 9.55219E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.11198E-04 | None | 0 | 0 | 5.71899E-06 | 0 | 0 |
| D/V | rs754343858 |
0.309 | 1.0 | D | 0.671 | 0.4 | 0.78964934489 | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | I | None | 0 | 2.83E-05 | None | 0 | 0 | None | 0 | None | 0 | 7.84E-06 | 1.40726E-04 |
| D/V | rs754343858 |
0.309 | 1.0 | D | 0.671 | 0.4 | 0.78964934489 | gnomAD-3.1.2 | 3.95E-05 | None | None | None | None | I | None | 2.41E-05 | 2.62123E-04 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/V | rs754343858 |
0.309 | 1.0 | D | 0.671 | 0.4 | 0.78964934489 | gnomAD-4.0.0 | 1.15356E-05 | None | None | None | None | I | None | 1.69188E-05 | 8.47745E-05 | None | 0 | 0 | None | 0 | 0 | 4.78829E-06 | 0 | 2.84511E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.6181 | likely_pathogenic | 0.68 | pathogenic | 0.013 | Stabilizing | 0.996 | D | 0.603 | neutral | D | 0.522467043 | None | None | I |
| D/C | 0.9536 | likely_pathogenic | 0.9644 | pathogenic | -0.089 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | I |
| D/E | 0.7427 | likely_pathogenic | 0.8092 | pathogenic | -0.182 | Destabilizing | 0.999 | D | 0.622 | neutral | D | 0.522720533 | None | None | I |
| D/F | 0.967 | likely_pathogenic | 0.9723 | pathogenic | 0.014 | Stabilizing | 1.0 | D | 0.688 | prob.neutral | None | None | None | None | I |
| D/G | 0.5678 | likely_pathogenic | 0.6671 | pathogenic | -0.142 | Destabilizing | 0.244 | N | 0.44 | neutral | D | 0.524494959 | None | None | I |
| D/H | 0.8722 | likely_pathogenic | 0.8942 | pathogenic | 0.469 | Stabilizing | 1.0 | D | 0.665 | neutral | D | 0.525508917 | None | None | I |
| D/I | 0.9615 | likely_pathogenic | 0.9716 | pathogenic | 0.362 | Stabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | I |
| D/K | 0.964 | likely_pathogenic | 0.9718 | pathogenic | 0.387 | Stabilizing | 1.0 | D | 0.642 | neutral | None | None | None | None | I |
| D/L | 0.8752 | likely_pathogenic | 0.8936 | pathogenic | 0.362 | Stabilizing | 1.0 | D | 0.676 | prob.neutral | None | None | None | None | I |
| D/M | 0.9702 | likely_pathogenic | 0.9776 | pathogenic | 0.182 | Stabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | I |
| D/N | 0.5803 | likely_pathogenic | 0.6584 | pathogenic | 0.162 | Stabilizing | 0.999 | D | 0.639 | neutral | N | 0.512124696 | None | None | I |
| D/P | 0.8941 | likely_pathogenic | 0.9093 | pathogenic | 0.267 | Stabilizing | 1.0 | D | 0.636 | neutral | None | None | None | None | I |
| D/Q | 0.9245 | likely_pathogenic | 0.9436 | pathogenic | 0.187 | Stabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | I |
| D/R | 0.9496 | likely_pathogenic | 0.9606 | pathogenic | 0.633 | Stabilizing | 1.0 | D | 0.658 | neutral | None | None | None | None | I |
| D/S | 0.4991 | ambiguous | 0.591 | pathogenic | 0.04 | Stabilizing | 0.997 | D | 0.667 | neutral | None | None | None | None | I |
| D/T | 0.8415 | likely_pathogenic | 0.8915 | pathogenic | 0.164 | Stabilizing | 1.0 | D | 0.628 | neutral | None | None | None | None | I |
| D/V | 0.8694 | likely_pathogenic | 0.8941 | pathogenic | 0.267 | Stabilizing | 1.0 | D | 0.671 | neutral | D | 0.525255428 | None | None | I |
| D/W | 0.9928 | likely_pathogenic | 0.9942 | pathogenic | 0.077 | Stabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | I |
| D/Y | 0.8376 | likely_pathogenic | 0.8541 | pathogenic | 0.244 | Stabilizing | 1.0 | D | 0.689 | prob.neutral | D | 0.525762407 | 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.