Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27213 | 81862;81863;81864 | chr2:178564495;178564494;178564493 | chr2:179429222;179429221;179429220 |
| N2AB | 25572 | 76939;76940;76941 | chr2:178564495;178564494;178564493 | chr2:179429222;179429221;179429220 |
| N2A | 24645 | 74158;74159;74160 | chr2:178564495;178564494;178564493 | chr2:179429222;179429221;179429220 |
| N2B | 18148 | 54667;54668;54669 | chr2:178564495;178564494;178564493 | chr2:179429222;179429221;179429220 |
| Novex-1 | 18273 | 55042;55043;55044 | chr2:178564495;178564494;178564493 | chr2:179429222;179429221;179429220 |
| Novex-2 | 18340 | 55243;55244;55245 | chr2:178564495;178564494;178564493 | chr2:179429222;179429221;179429220 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | None | None | 0.976 | N | 0.643 | 0.452 | 0.568358697712 | gnomAD-4.0.0 | 1.59542E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86457E-06 | 0 | 0 |
| P/S | rs375058735  |
None | 0.976 | N | 0.526 | 0.31 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | rs375058735 |
None | 0.976 | N | 0.526 | 0.31 | None | gnomAD-4.0.0 | 6.57298E-06 | None | None | None | None | N | None | 2.41313E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/T | rs375058735 |
-0.277 | 0.988 | N | 0.557 | 0.406 | None | gnomAD-2.1.1 | 4.09E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.09E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.3249 | likely_benign | 0.277 | benign | -0.366 | Destabilizing | 0.067 | N | 0.411 | neutral | N | 0.50670437 | None | None | N |
| P/C | 0.8762 | likely_pathogenic | 0.8397 | pathogenic | -0.777 | Destabilizing | 0.999 | D | 0.688 | prob.neutral | None | None | None | None | N |
| P/D | 0.8069 | likely_pathogenic | 0.7785 | pathogenic | -0.356 | Destabilizing | 0.995 | D | 0.595 | neutral | None | None | None | None | N |
| P/E | 0.6747 | likely_pathogenic | 0.6189 | pathogenic | -0.474 | Destabilizing | 0.991 | D | 0.587 | neutral | None | None | None | None | N |
| P/F | 0.9204 | likely_pathogenic | 0.8885 | pathogenic | -0.686 | Destabilizing | 0.999 | D | 0.683 | prob.neutral | None | None | None | None | N |
| P/G | 0.6063 | likely_pathogenic | 0.5758 | pathogenic | -0.445 | Destabilizing | 0.938 | D | 0.518 | neutral | None | None | None | None | N |
| P/H | 0.676 | likely_pathogenic | 0.6084 | pathogenic | 0.023 | Stabilizing | 0.999 | D | 0.643 | neutral | N | 0.481622227 | None | None | N |
| P/I | 0.7849 | likely_pathogenic | 0.7205 | pathogenic | -0.307 | Destabilizing | 0.991 | D | 0.687 | prob.neutral | None | None | None | None | N |
| P/K | 0.7268 | likely_pathogenic | 0.6712 | pathogenic | -0.404 | Destabilizing | 0.991 | D | 0.594 | neutral | None | None | None | None | N |
| P/L | 0.4526 | ambiguous | 0.3806 | ambiguous | -0.307 | Destabilizing | 0.976 | D | 0.643 | neutral | N | 0.474531882 | None | None | N |
| P/M | 0.7544 | likely_pathogenic | 0.699 | pathogenic | -0.522 | Destabilizing | 1.0 | D | 0.64 | neutral | None | None | None | None | N |
| P/N | 0.769 | likely_pathogenic | 0.723 | pathogenic | -0.216 | Destabilizing | 0.995 | D | 0.645 | neutral | None | None | None | None | N |
| P/Q | 0.5939 | likely_pathogenic | 0.5357 | ambiguous | -0.444 | Destabilizing | 0.995 | D | 0.593 | neutral | None | None | None | None | N |
| P/R | 0.6087 | likely_pathogenic | 0.5355 | ambiguous | 0.096 | Stabilizing | 0.994 | D | 0.649 | neutral | N | 0.511494114 | None | None | N |
| P/S | 0.5189 | ambiguous | 0.4519 | ambiguous | -0.534 | Destabilizing | 0.976 | D | 0.526 | neutral | N | 0.492561637 | None | None | N |
| P/T | 0.3754 | ambiguous | 0.3236 | benign | -0.556 | Destabilizing | 0.988 | D | 0.557 | neutral | N | 0.509339244 | None | None | N |
| P/V | 0.6513 | likely_pathogenic | 0.5869 | pathogenic | -0.296 | Destabilizing | 0.982 | D | 0.569 | neutral | None | None | None | None | N |
| P/W | 0.9529 | likely_pathogenic | 0.9339 | pathogenic | -0.741 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | N |
| P/Y | 0.8883 | likely_pathogenic | 0.8535 | pathogenic | -0.462 | Destabilizing | 1.0 | D | 0.682 | prob.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.