Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13815 | 41668;41669;41670 | chr2:178636128;178636127;178636126 | chr2:179500855;179500854;179500853 |
| N2AB | 12174 | 36745;36746;36747 | chr2:178636128;178636127;178636126 | chr2:179500855;179500854;179500853 |
| N2A | 11247 | 33964;33965;33966 | chr2:178636128;178636127;178636126 | chr2:179500855;179500854;179500853 |
| N2B | 4750 | 14473;14474;14475 | chr2:178636128;178636127;178636126 | chr2:179500855;179500854;179500853 |
| Novex-1 | 4875 | 14848;14849;14850 | chr2:178636128;178636127;178636126 | chr2:179500855;179500854;179500853 |
| Novex-2 | 4942 | 15049;15050;15051 | chr2:178636128;178636127;178636126 | chr2:179500855;179500854;179500853 |
| 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/G | rs771949273  |
-0.286 | 0.955 | N | 0.499 | 0.351 | 0.168933306366 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 9.81E-05 | None | 0 | 0 | 0 |
| D/G | rs771949273 |
-0.286 | 0.955 | N | 0.499 | 0.351 | 0.168933306366 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07383E-04 | 0 |
| D/G | rs771949273 |
-0.286 | 0.955 | N | 0.499 | 0.351 | 0.168933306366 | gnomAD-4.0.0 | 7.43927E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.31793E-04 | 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 | 0.8313 | likely_pathogenic | 0.8276 | pathogenic | -0.522 | Destabilizing | 0.993 | D | 0.585 | neutral | N | 0.374769848 | None | None | N |
| D/C | 0.9702 | likely_pathogenic | 0.9664 | pathogenic | -0.12 | Destabilizing | 1.0 | D | 0.689 | prob.delet. | None | None | None | None | N |
| D/E | 0.7596 | likely_pathogenic | 0.7622 | pathogenic | -0.312 | Destabilizing | 0.977 | D | 0.447 | neutral | N | 0.335492785 | None | None | N |
| D/F | 0.9829 | likely_pathogenic | 0.9799 | pathogenic | -0.233 | Destabilizing | 1.0 | D | 0.667 | prob.neutral | None | None | None | None | N |
| D/G | 0.5428 | ambiguous | 0.5562 | ambiguous | -0.759 | Destabilizing | 0.955 | D | 0.499 | neutral | N | 0.343653622 | None | None | N |
| D/H | 0.94 | likely_pathogenic | 0.9302 | pathogenic | -0.115 | Destabilizing | 0.999 | D | 0.609 | neutral | N | 0.413689135 | None | None | N |
| D/I | 0.9872 | likely_pathogenic | 0.9861 | pathogenic | 0.073 | Stabilizing | 0.999 | D | 0.706 | prob.delet. | None | None | None | None | N |
| D/K | 0.9753 | likely_pathogenic | 0.9704 | pathogenic | 0.172 | Stabilizing | 0.995 | D | 0.659 | prob.neutral | None | None | None | None | N |
| D/L | 0.9693 | likely_pathogenic | 0.9628 | pathogenic | 0.073 | Stabilizing | 0.998 | D | 0.698 | prob.delet. | None | None | None | None | N |
| D/M | 0.9888 | likely_pathogenic | 0.987 | pathogenic | 0.278 | Stabilizing | 1.0 | D | 0.693 | prob.delet. | None | None | None | None | N |
| D/N | 0.2361 | likely_benign | 0.2859 | benign | -0.28 | Destabilizing | 0.117 | N | 0.252 | neutral | N | 0.346909104 | None | None | N |
| D/P | 0.9988 | likely_pathogenic | 0.9988 | pathogenic | -0.103 | Destabilizing | 0.999 | D | 0.642 | neutral | None | None | None | None | N |
| D/Q | 0.9547 | likely_pathogenic | 0.9468 | pathogenic | -0.207 | Destabilizing | 0.998 | D | 0.589 | neutral | None | None | None | None | N |
| D/R | 0.9727 | likely_pathogenic | 0.9676 | pathogenic | 0.391 | Stabilizing | 0.995 | D | 0.627 | neutral | None | None | None | None | N |
| D/S | 0.6204 | likely_pathogenic | 0.6422 | pathogenic | -0.401 | Destabilizing | 0.966 | D | 0.461 | neutral | None | None | None | None | N |
| D/T | 0.952 | likely_pathogenic | 0.9521 | pathogenic | -0.202 | Destabilizing | 0.995 | D | 0.658 | prob.neutral | None | None | None | None | N |
| D/V | 0.9559 | likely_pathogenic | 0.9508 | pathogenic | -0.103 | Destabilizing | 0.997 | D | 0.685 | prob.delet. | N | 0.413689135 | None | None | N |
| D/W | 0.9962 | likely_pathogenic | 0.9953 | pathogenic | -0.002 | Destabilizing | 1.0 | D | 0.627 | neutral | None | None | None | None | N |
| D/Y | 0.859 | likely_pathogenic | 0.8412 | pathogenic | 0.026 | Stabilizing | 1.0 | D | 0.666 | prob.neutral | N | 0.450323085 | 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.