Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1842 | 5749;5750;5751 | chr2:178776340;178776339;178776338 | chr2:179641067;179641066;179641065 |
| N2AB | 1842 | 5749;5750;5751 | chr2:178776340;178776339;178776338 | chr2:179641067;179641066;179641065 |
| N2A | 1842 | 5749;5750;5751 | chr2:178776340;178776339;178776338 | chr2:179641067;179641066;179641065 |
| N2B | 1796 | 5611;5612;5613 | chr2:178776340;178776339;178776338 | chr2:179641067;179641066;179641065 |
| Novex-1 | 1796 | 5611;5612;5613 | chr2:178776340;178776339;178776338 | chr2:179641067;179641066;179641065 |
| Novex-2 | 1796 | 5611;5612;5613 | chr2:178776340;178776339;178776338 | chr2:179641067;179641066;179641065 |
| Novex-3 | 1842 | 5749;5750;5751 | chr2:178776340;178776339;178776338 | chr2:179641067;179641066;179641065 |
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/H | None | None | 0.998 | N | 0.487 | 0.43 | 0.388174495139 | gnomAD-4.0.0 | 6.84204E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65579E-05 |
| D/N | rs1469586209  |
0.063 | 0.939 | N | 0.415 | 0.25 | 0.405150804464 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 2.89E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/N | rs1469586209 |
0.063 | 0.939 | N | 0.415 | 0.25 | 0.405150804464 | gnomAD-4.0.0 | 6.84204E-07 | None | None | None | None | N | None | 0 | 2.23614E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 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 | 0.2212 | likely_benign | 0.248 | benign | -0.151 | Destabilizing | 0.939 | D | 0.417 | neutral | N | 0.458646154 | None | None | N |
| D/C | 0.7659 | likely_pathogenic | 0.83 | pathogenic | -0.162 | Destabilizing | 0.999 | D | 0.679 | prob.neutral | None | None | None | None | N |
| D/E | 0.1043 | likely_benign | 0.1154 | benign | -0.37 | Destabilizing | 0.02 | N | 0.192 | neutral | N | 0.379063398 | None | None | N |
| D/F | 0.7378 | likely_pathogenic | 0.7928 | pathogenic | 0.385 | Stabilizing | 0.998 | D | 0.625 | neutral | None | None | None | None | N |
| D/G | 0.3281 | likely_benign | 0.3587 | ambiguous | -0.456 | Destabilizing | 0.939 | D | 0.43 | neutral | N | 0.49887892 | None | None | N |
| D/H | 0.4168 | ambiguous | 0.505 | ambiguous | 0.53 | Stabilizing | 0.998 | D | 0.487 | neutral | N | 0.485155052 | None | None | N |
| D/I | 0.4344 | ambiguous | 0.4904 | ambiguous | 0.635 | Stabilizing | 0.993 | D | 0.626 | neutral | None | None | None | None | N |
| D/K | 0.4983 | ambiguous | 0.5545 | ambiguous | 0.196 | Stabilizing | 0.91 | D | 0.423 | neutral | None | None | None | None | N |
| D/L | 0.495 | ambiguous | 0.5549 | ambiguous | 0.635 | Stabilizing | 0.986 | D | 0.617 | neutral | None | None | None | None | N |
| D/M | 0.659 | likely_pathogenic | 0.7125 | pathogenic | 0.638 | Stabilizing | 0.999 | D | 0.633 | neutral | None | None | None | None | N |
| D/N | 0.1302 | likely_benign | 0.132 | benign | -0.444 | Destabilizing | 0.939 | D | 0.415 | neutral | N | 0.484623344 | None | None | N |
| D/P | 0.9736 | likely_pathogenic | 0.986 | pathogenic | 0.398 | Stabilizing | 0.993 | D | 0.497 | neutral | None | None | None | None | N |
| D/Q | 0.3518 | ambiguous | 0.406 | ambiguous | -0.304 | Destabilizing | 0.973 | D | 0.415 | neutral | None | None | None | None | N |
| D/R | 0.5446 | ambiguous | 0.6173 | pathogenic | 0.525 | Stabilizing | 0.986 | D | 0.571 | neutral | None | None | None | None | N |
| D/S | 0.1626 | likely_benign | 0.1675 | benign | -0.577 | Destabilizing | 0.953 | D | 0.403 | neutral | None | None | None | None | N |
| D/T | 0.2802 | likely_benign | 0.3166 | benign | -0.314 | Destabilizing | 0.986 | D | 0.44 | neutral | None | None | None | None | N |
| D/V | 0.258 | likely_benign | 0.2937 | benign | 0.398 | Stabilizing | 0.991 | D | 0.605 | neutral | N | 0.432393601 | None | None | N |
| D/W | 0.9477 | likely_pathogenic | 0.9681 | pathogenic | 0.597 | Stabilizing | 0.999 | D | 0.675 | prob.neutral | None | None | None | None | N |
| D/Y | 0.4193 | ambiguous | 0.4802 | ambiguous | 0.658 | Stabilizing | 0.997 | D | 0.627 | neutral | N | 0.458431568 | 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.