Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28361 | 85306;85307;85308 | chr2:178561051;178561050;178561049 | chr2:179425778;179425777;179425776 |
| N2AB | 26720 | 80383;80384;80385 | chr2:178561051;178561050;178561049 | chr2:179425778;179425777;179425776 |
| N2A | 25793 | 77602;77603;77604 | chr2:178561051;178561050;178561049 | chr2:179425778;179425777;179425776 |
| N2B | 19296 | 58111;58112;58113 | chr2:178561051;178561050;178561049 | chr2:179425778;179425777;179425776 |
| Novex-1 | 19421 | 58486;58487;58488 | chr2:178561051;178561050;178561049 | chr2:179425778;179425777;179425776 |
| Novex-2 | 19488 | 58687;58688;58689 | chr2:178561051;178561050;178561049 | chr2:179425778;179425777;179425776 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs1428136058  |
-1.531 | 0.005 | N | 0.187 | 0.104 | 0.442466506703 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.65673E-04 |
| V/A | rs1428136058 |
-1.531 | 0.005 | N | 0.187 | 0.104 | 0.442466506703 | gnomAD-4.0.0 | 4.77321E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85798E-06 | 0 | 6.04741E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2389 | likely_benign | 0.1922 | benign | -0.499 | Destabilizing | 0.005 | N | 0.187 | neutral | N | 0.414994649 | None | None | N |
| V/C | 0.7942 | likely_pathogenic | 0.7644 | pathogenic | -0.625 | Destabilizing | 0.998 | D | 0.503 | neutral | None | None | None | None | N |
| V/D | 0.4354 | ambiguous | 0.381 | ambiguous | -0.517 | Destabilizing | 0.005 | N | 0.368 | neutral | N | 0.431158967 | None | None | N |
| V/E | 0.3943 | ambiguous | 0.3599 | ambiguous | -0.629 | Destabilizing | 0.728 | D | 0.441 | neutral | None | None | None | None | N |
| V/F | 0.2918 | likely_benign | 0.2544 | benign | -0.728 | Destabilizing | 0.934 | D | 0.526 | neutral | N | 0.517065797 | None | None | N |
| V/G | 0.2677 | likely_benign | 0.2236 | benign | -0.623 | Destabilizing | 0.669 | D | 0.465 | neutral | N | 0.445955061 | None | None | N |
| V/H | 0.708 | likely_pathogenic | 0.6532 | pathogenic | -0.171 | Destabilizing | 0.998 | D | 0.558 | neutral | None | None | None | None | N |
| V/I | 0.1072 | likely_benign | 0.0991 | benign | -0.316 | Destabilizing | 0.454 | N | 0.467 | neutral | N | 0.497786603 | None | None | N |
| V/K | 0.4948 | ambiguous | 0.457 | ambiguous | -0.551 | Destabilizing | 0.842 | D | 0.471 | neutral | None | None | None | None | N |
| V/L | 0.3266 | likely_benign | 0.2656 | benign | -0.316 | Destabilizing | 0.012 | N | 0.19 | neutral | N | 0.485876099 | None | None | N |
| V/M | 0.2425 | likely_benign | 0.1883 | benign | -0.431 | Destabilizing | 0.949 | D | 0.567 | neutral | None | None | None | None | N |
| V/N | 0.4117 | ambiguous | 0.3391 | benign | -0.284 | Destabilizing | 0.949 | D | 0.553 | neutral | None | None | None | None | N |
| V/P | 0.4359 | ambiguous | 0.3831 | ambiguous | -0.343 | Destabilizing | 0.974 | D | 0.541 | neutral | None | None | None | None | N |
| V/Q | 0.4611 | ambiguous | 0.4144 | ambiguous | -0.533 | Destabilizing | 0.974 | D | 0.549 | neutral | None | None | None | None | N |
| V/R | 0.427 | ambiguous | 0.4001 | ambiguous | -0.001 | Destabilizing | 0.974 | D | 0.571 | neutral | None | None | None | None | N |
| V/S | 0.2943 | likely_benign | 0.2388 | benign | -0.594 | Destabilizing | 0.728 | D | 0.443 | neutral | None | None | None | None | N |
| V/T | 0.3175 | likely_benign | 0.2561 | benign | -0.611 | Destabilizing | 0.842 | D | 0.461 | neutral | None | None | None | None | N |
| V/W | 0.8739 | likely_pathogenic | 0.8326 | pathogenic | -0.816 | Destabilizing | 0.998 | D | 0.608 | neutral | None | None | None | None | N |
| V/Y | 0.6396 | likely_pathogenic | 0.5981 | pathogenic | -0.528 | Destabilizing | 0.991 | D | 0.541 | neutral | None | None | 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.