Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19627 | 59104;59105;59106 | chr2:178593329;178593328;178593327 | chr2:179458056;179458055;179458054 |
| N2AB | 17986 | 54181;54182;54183 | chr2:178593329;178593328;178593327 | chr2:179458056;179458055;179458054 |
| N2A | 17059 | 51400;51401;51402 | chr2:178593329;178593328;178593327 | chr2:179458056;179458055;179458054 |
| N2B | 10562 | 31909;31910;31911 | chr2:178593329;178593328;178593327 | chr2:179458056;179458055;179458054 |
| Novex-1 | 10687 | 32284;32285;32286 | chr2:178593329;178593328;178593327 | chr2:179458056;179458055;179458054 |
| Novex-2 | 10754 | 32485;32486;32487 | chr2:178593329;178593328;178593327 | chr2:179458056;179458055;179458054 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | rs1416921994  |
-0.557 | 0.625 | N | 0.514 | 0.239 | 0.422040124859 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/G | rs1416921994 |
-0.557 | 0.625 | N | 0.514 | 0.239 | 0.422040124859 | gnomAD-4.0.0 | 1.59201E-06 | None | None | None | None | N | None | 5.66251E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/S | rs748773320 |
-0.462 | 0.454 | N | 0.51 | 0.186 | 0.257786959452 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.87E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.6424 | likely_pathogenic | 0.5431 | ambiguous | -0.175 | Destabilizing | 0.029 | N | 0.263 | neutral | None | None | None | None | N |
| R/C | 0.4135 | ambiguous | 0.3096 | benign | -0.168 | Destabilizing | 0.998 | D | 0.553 | neutral | None | None | None | None | N |
| R/D | 0.9197 | likely_pathogenic | 0.8928 | pathogenic | 0.091 | Stabilizing | 0.842 | D | 0.597 | neutral | None | None | None | None | N |
| R/E | 0.707 | likely_pathogenic | 0.6287 | pathogenic | 0.193 | Stabilizing | 0.728 | D | 0.502 | neutral | None | None | None | None | N |
| R/F | 0.7935 | likely_pathogenic | 0.7353 | pathogenic | -0.129 | Destabilizing | 0.991 | D | 0.576 | neutral | None | None | None | None | N |
| R/G | 0.645 | likely_pathogenic | 0.5313 | ambiguous | -0.448 | Destabilizing | 0.625 | D | 0.514 | neutral | N | 0.475825783 | None | None | N |
| R/H | 0.2559 | likely_benign | 0.204 | benign | -0.916 | Destabilizing | 0.991 | D | 0.573 | neutral | None | None | None | None | N |
| R/I | 0.5062 | ambiguous | 0.4139 | ambiguous | 0.533 | Stabilizing | 0.966 | D | 0.57 | neutral | D | 0.522444614 | None | None | N |
| R/K | 0.1297 | likely_benign | 0.1121 | benign | -0.21 | Destabilizing | 0.005 | N | 0.179 | neutral | N | 0.435921707 | None | None | N |
| R/L | 0.4661 | ambiguous | 0.3755 | ambiguous | 0.533 | Stabilizing | 0.842 | D | 0.533 | neutral | None | None | None | None | N |
| R/M | 0.5221 | ambiguous | 0.4123 | ambiguous | 0.065 | Stabilizing | 0.991 | D | 0.575 | neutral | None | None | None | None | N |
| R/N | 0.8649 | likely_pathogenic | 0.8144 | pathogenic | 0.192 | Stabilizing | 0.842 | D | 0.531 | neutral | None | None | None | None | N |
| R/P | 0.5932 | likely_pathogenic | 0.5134 | ambiguous | 0.319 | Stabilizing | 0.974 | D | 0.579 | neutral | None | None | None | None | N |
| R/Q | 0.2266 | likely_benign | 0.182 | benign | 0.085 | Stabilizing | 0.842 | D | 0.536 | neutral | None | None | None | None | N |
| R/S | 0.828 | likely_pathogenic | 0.7558 | pathogenic | -0.319 | Destabilizing | 0.454 | N | 0.51 | neutral | N | 0.519460237 | None | None | N |
| R/T | 0.5561 | ambiguous | 0.4376 | ambiguous | -0.054 | Destabilizing | 0.801 | D | 0.527 | neutral | N | 0.463260237 | None | None | N |
| R/V | 0.5368 | ambiguous | 0.4505 | ambiguous | 0.319 | Stabilizing | 0.842 | D | 0.552 | neutral | None | None | None | None | N |
| R/W | 0.3944 | ambiguous | 0.3207 | benign | None | Stabilizing | 0.998 | D | 0.581 | neutral | None | None | None | None | N |
| R/Y | 0.6698 | likely_pathogenic | 0.6068 | pathogenic | 0.352 | Stabilizing | 0.991 | D | 0.597 | 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.