Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27211 | 81856;81857;81858 | chr2:178564501;178564500;178564499 | chr2:179429228;179429227;179429226 |
| N2AB | 25570 | 76933;76934;76935 | chr2:178564501;178564500;178564499 | chr2:179429228;179429227;179429226 |
| N2A | 24643 | 74152;74153;74154 | chr2:178564501;178564500;178564499 | chr2:179429228;179429227;179429226 |
| N2B | 18146 | 54661;54662;54663 | chr2:178564501;178564500;178564499 | chr2:179429228;179429227;179429226 |
| Novex-1 | 18271 | 55036;55037;55038 | chr2:178564501;178564500;178564499 | chr2:179429228;179429227;179429226 |
| Novex-2 | 18338 | 55237;55238;55239 | chr2:178564501;178564500;178564499 | chr2:179429228;179429227;179429226 |
| 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/N | rs747343429  |
-1.31 | 0.801 | N | 0.48 | 0.288 | 0.36453787251 | gnomAD-2.1.1 | 4.09E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.08E-06 | 0 |
| D/N | rs747343429 |
-1.31 | 0.801 | N | 0.48 | 0.288 | 0.36453787251 | gnomAD-4.0.0 | 2.73964E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.53241E-05 | None | 0 | 0 | 0 | 0 | 4.97595E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2627 | likely_benign | 0.236 | benign | -0.609 | Destabilizing | 0.801 | D | 0.504 | neutral | N | 0.470937484 | None | None | N |
| D/C | 0.7865 | likely_pathogenic | 0.7463 | pathogenic | -0.387 | Destabilizing | 0.998 | D | 0.647 | neutral | None | None | None | None | N |
| D/E | 0.1409 | likely_benign | 0.1404 | benign | -0.826 | Destabilizing | 0.005 | N | 0.085 | neutral | N | 0.400267551 | None | None | N |
| D/F | 0.7742 | likely_pathogenic | 0.724 | pathogenic | -0.282 | Destabilizing | 0.991 | D | 0.611 | neutral | None | None | None | None | N |
| D/G | 0.4121 | ambiguous | 0.3585 | ambiguous | -1.018 | Destabilizing | 0.801 | D | 0.437 | neutral | N | 0.496508806 | None | None | N |
| D/H | 0.614 | likely_pathogenic | 0.5567 | ambiguous | -0.704 | Destabilizing | 0.966 | D | 0.523 | neutral | N | 0.490055697 | None | None | N |
| D/I | 0.4129 | ambiguous | 0.3812 | ambiguous | 0.493 | Stabilizing | 0.974 | D | 0.618 | neutral | None | None | None | None | N |
| D/K | 0.6799 | likely_pathogenic | 0.6303 | pathogenic | -0.817 | Destabilizing | 0.029 | N | 0.153 | neutral | None | None | None | None | N |
| D/L | 0.4647 | ambiguous | 0.4209 | ambiguous | 0.493 | Stabilizing | 0.949 | D | 0.527 | neutral | None | None | None | None | N |
| D/M | 0.6532 | likely_pathogenic | 0.6163 | pathogenic | 1.036 | Stabilizing | 0.998 | D | 0.594 | neutral | None | None | None | None | N |
| D/N | 0.2013 | likely_benign | 0.1696 | benign | -1.176 | Destabilizing | 0.801 | D | 0.48 | neutral | N | 0.521943181 | None | None | N |
| D/P | 0.7073 | likely_pathogenic | 0.6882 | pathogenic | 0.151 | Stabilizing | 0.974 | D | 0.444 | neutral | None | None | None | None | N |
| D/Q | 0.5156 | ambiguous | 0.4836 | ambiguous | -0.952 | Destabilizing | 0.728 | D | 0.425 | neutral | None | None | None | None | N |
| D/R | 0.7476 | likely_pathogenic | 0.6992 | pathogenic | -0.735 | Destabilizing | 0.728 | D | 0.497 | neutral | None | None | None | None | N |
| D/S | 0.2602 | likely_benign | 0.2324 | benign | -1.605 | Destabilizing | 0.842 | D | 0.437 | neutral | None | None | None | None | N |
| D/T | 0.397 | ambiguous | 0.377 | ambiguous | -1.256 | Destabilizing | 0.842 | D | 0.441 | neutral | None | None | None | None | N |
| D/V | 0.2488 | likely_benign | 0.2313 | benign | 0.151 | Stabilizing | 0.966 | D | 0.537 | neutral | N | 0.476724382 | None | None | N |
| D/W | 0.9511 | likely_pathogenic | 0.9402 | pathogenic | -0.254 | Destabilizing | 0.998 | D | 0.679 | prob.neutral | None | None | None | None | N |
| D/Y | 0.4075 | ambiguous | 0.3458 | ambiguous | -0.076 | Destabilizing | 0.989 | D | 0.611 | neutral | N | 0.51394685 | 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.