Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 6824 | 20695;20696;20697 | chr2:178725852;178725851;178725850 | chr2:179590579;179590578;179590577 |
| N2AB | 6507 | 19744;19745;19746 | chr2:178725852;178725851;178725850 | chr2:179590579;179590578;179590577 |
| N2A | 5580 | 16963;16964;16965 | chr2:178725852;178725851;178725850 | chr2:179590579;179590578;179590577 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 | rs1418781337  |
-0.308 | None | N | 0.117 | 0.169 | 0.0666544352282 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.66556E-04 |
| D/E | rs1418781337 |
-0.308 | None | N | 0.117 | 0.169 | 0.0666544352282 | gnomAD-4.0.0 | 6.84434E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.29777E-06 | 0 | 4.97216E-05 |
| D/N | rs1177053668 |
0.078 | 0.018 | N | 0.365 | 0.119 | 0.270001397563 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 1.39509E-04 | 0 | 0 |
| D/N | rs1177053668 |
0.078 | 0.018 | N | 0.365 | 0.119 | 0.270001397563 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 9.42E-05 | 0 | 0 | 0 | 0 |
| D/N | rs1177053668 |
0.078 | 0.018 | N | 0.365 | 0.119 | 0.270001397563 | gnomAD-4.0.0 | 7.6917E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 9.41827E-05 | 0 | 0 | 0 | 0 |
| D/Y | rs1177053668 |
-0.397 | 0.864 | N | 0.487 | 0.241 | 0.473774312618 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| D/Y | rs1177053668 |
-0.397 | 0.864 | N | 0.487 | 0.241 | 0.473774312618 | gnomAD-4.0.0 | 1.5925E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86049E-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 | 0.1756 | likely_benign | 0.1745 | benign | -0.428 | Destabilizing | 0.017 | N | 0.426 | neutral | N | 0.495770592 | None | None | N |
| D/C | 0.6241 | likely_pathogenic | 0.6292 | pathogenic | 0.075 | Stabilizing | 0.718 | D | 0.46 | neutral | None | None | None | None | N |
| D/E | 0.1 | likely_benign | 0.0932 | benign | -0.475 | Destabilizing | None | N | 0.117 | neutral | N | 0.429121526 | None | None | N |
| D/F | 0.642 | likely_pathogenic | 0.632 | pathogenic | -0.377 | Destabilizing | 0.734 | D | 0.482 | neutral | None | None | None | None | N |
| D/G | 0.172 | likely_benign | 0.1679 | benign | -0.687 | Destabilizing | 0.012 | N | 0.416 | neutral | N | 0.485324312 | None | None | N |
| D/H | 0.3285 | likely_benign | 0.3573 | ambiguous | -0.571 | Destabilizing | 0.438 | N | 0.405 | neutral | N | 0.484580374 | None | None | N |
| D/I | 0.3915 | ambiguous | 0.3819 | ambiguous | 0.222 | Stabilizing | 0.734 | D | 0.504 | neutral | None | None | None | None | N |
| D/K | 0.4065 | ambiguous | 0.4228 | ambiguous | 0.093 | Stabilizing | 0.074 | N | 0.413 | neutral | None | None | None | None | N |
| D/L | 0.3964 | ambiguous | 0.3874 | ambiguous | 0.222 | Stabilizing | 0.28 | N | 0.475 | neutral | None | None | None | None | N |
| D/M | 0.5633 | ambiguous | 0.54 | ambiguous | 0.637 | Stabilizing | 0.759 | D | 0.456 | neutral | None | None | None | None | N |
| D/N | 0.107 | likely_benign | 0.1123 | benign | -0.27 | Destabilizing | 0.018 | N | 0.365 | neutral | N | 0.49873354 | None | None | N |
| D/P | 0.8791 | likely_pathogenic | 0.837 | pathogenic | 0.029 | Stabilizing | 0.015 | N | 0.436 | neutral | None | None | None | None | N |
| D/Q | 0.2891 | likely_benign | 0.2966 | benign | -0.194 | Destabilizing | 0.006 | N | 0.172 | neutral | None | None | None | None | N |
| D/R | 0.4868 | ambiguous | 0.498 | ambiguous | 0.142 | Stabilizing | 0.163 | N | 0.476 | neutral | None | None | None | None | N |
| D/S | 0.1234 | likely_benign | 0.1237 | benign | -0.409 | Destabilizing | 0.001 | N | 0.129 | neutral | None | None | None | None | N |
| D/T | 0.2199 | likely_benign | 0.2227 | benign | -0.2 | Destabilizing | 0.024 | N | 0.423 | neutral | None | None | None | None | N |
| D/V | 0.2518 | likely_benign | 0.246 | benign | 0.029 | Stabilizing | 0.049 | N | 0.496 | neutral | N | 0.511798838 | None | None | N |
| D/W | 0.9161 | likely_pathogenic | 0.9048 | pathogenic | -0.254 | Destabilizing | 0.969 | D | 0.517 | neutral | None | None | None | None | N |
| D/Y | 0.3431 | ambiguous | 0.351 | ambiguous | -0.149 | Destabilizing | 0.864 | D | 0.487 | neutral | N | 0.484833864 | 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.