Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24383 | 73372;73373;73374 | chr2:178572985;178572984;178572983 | chr2:179437712;179437711;179437710 |
| N2AB | 22742 | 68449;68450;68451 | chr2:178572985;178572984;178572983 | chr2:179437712;179437711;179437710 |
| N2A | 21815 | 65668;65669;65670 | chr2:178572985;178572984;178572983 | chr2:179437712;179437711;179437710 |
| N2B | 15318 | 46177;46178;46179 | chr2:178572985;178572984;178572983 | chr2:179437712;179437711;179437710 |
| Novex-1 | 15443 | 46552;46553;46554 | chr2:178572985;178572984;178572983 | chr2:179437712;179437711;179437710 |
| Novex-2 | 15510 | 46753;46754;46755 | chr2:178572985;178572984;178572983 | chr2:179437712;179437711;179437710 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/L | rs368415251  |
0.436 | 0.98 | N | 0.596 | 0.321 | None | gnomAD-2.1.1 | 1.79E-05 | None | None | None | None | I | None | 1.65659E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 7.85E-06 | 0 |
| S/L | rs368415251 |
0.436 | 0.98 | N | 0.596 | 0.321 | None | gnomAD-3.1.2 | 3.95E-05 | None | None | None | None | I | None | 1.44788E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/L | rs368415251 |
0.436 | 0.98 | N | 0.596 | 0.321 | None | gnomAD-4.0.0 | 7.4395E-06 | None | None | None | None | I | None | 1.3354E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69562E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0857 | likely_benign | 0.0848 | benign | -0.646 | Destabilizing | 0.78 | D | 0.478 | neutral | N | 0.486275957 | None | None | I |
| S/C | 0.1067 | likely_benign | 0.0979 | benign | -0.366 | Destabilizing | 0.999 | D | 0.671 | neutral | None | None | None | None | I |
| S/D | 0.5499 | ambiguous | 0.5981 | pathogenic | 0.58 | Stabilizing | 0.959 | D | 0.496 | neutral | None | None | None | None | I |
| S/E | 0.5324 | ambiguous | 0.5518 | ambiguous | 0.612 | Stabilizing | 0.919 | D | 0.461 | neutral | None | None | None | None | I |
| S/F | 0.2564 | likely_benign | 0.265 | benign | -0.964 | Destabilizing | 0.996 | D | 0.718 | prob.delet. | None | None | None | None | I |
| S/G | 0.1101 | likely_benign | 0.1157 | benign | -0.886 | Destabilizing | 0.959 | D | 0.472 | neutral | None | None | None | None | I |
| S/H | 0.311 | likely_benign | 0.331 | benign | -1.102 | Destabilizing | 0.997 | D | 0.678 | prob.neutral | None | None | None | None | I |
| S/I | 0.2087 | likely_benign | 0.2044 | benign | -0.108 | Destabilizing | 0.988 | D | 0.689 | prob.neutral | None | None | None | None | I |
| S/K | 0.6373 | likely_pathogenic | 0.6758 | pathogenic | -0.046 | Destabilizing | 0.132 | N | 0.437 | neutral | None | None | None | None | I |
| S/L | 0.1424 | likely_benign | 0.1391 | benign | -0.108 | Destabilizing | 0.98 | D | 0.596 | neutral | N | 0.477185817 | None | None | I |
| S/M | 0.2075 | likely_benign | 0.2095 | benign | -0.171 | Destabilizing | 0.999 | D | 0.675 | neutral | None | None | None | None | I |
| S/N | 0.1429 | likely_benign | 0.1555 | benign | -0.158 | Destabilizing | 0.919 | D | 0.487 | neutral | None | None | None | None | I |
| S/P | 0.9267 | likely_pathogenic | 0.9238 | pathogenic | -0.255 | Destabilizing | 0.995 | D | 0.633 | neutral | N | 0.476932327 | None | None | I |
| S/Q | 0.4318 | ambiguous | 0.4533 | ambiguous | -0.149 | Destabilizing | 0.976 | D | 0.533 | neutral | None | None | None | None | I |
| S/R | 0.5398 | ambiguous | 0.5815 | pathogenic | -0.075 | Destabilizing | 0.076 | N | 0.4 | neutral | None | None | None | None | I |
| S/T | 0.0805 | likely_benign | 0.0804 | benign | -0.231 | Destabilizing | 0.946 | D | 0.479 | neutral | N | 0.472517226 | None | None | I |
| S/V | 0.196 | likely_benign | 0.1836 | benign | -0.255 | Destabilizing | 0.988 | D | 0.63 | neutral | None | None | None | None | I |
| S/W | 0.459 | ambiguous | 0.4741 | ambiguous | -0.974 | Destabilizing | 0.999 | D | 0.724 | prob.delet. | N | 0.514154796 | None | None | I |
| S/Y | 0.2126 | likely_benign | 0.2251 | benign | -0.629 | Destabilizing | 0.996 | D | 0.718 | prob.delet. | None | None | 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.