Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23870 | 71833;71834;71835 | chr2:178574524;178574523;178574522 | chr2:179439251;179439250;179439249 |
| N2AB | 22229 | 66910;66911;66912 | chr2:178574524;178574523;178574522 | chr2:179439251;179439250;179439249 |
| N2A | 21302 | 64129;64130;64131 | chr2:178574524;178574523;178574522 | chr2:179439251;179439250;179439249 |
| N2B | 14805 | 44638;44639;44640 | chr2:178574524;178574523;178574522 | chr2:179439251;179439250;179439249 |
| Novex-1 | 14930 | 45013;45014;45015 | chr2:178574524;178574523;178574522 | chr2:179439251;179439250;179439249 |
| Novex-2 | 14997 | 45214;45215;45216 | chr2:178574524;178574523;178574522 | chr2:179439251;179439250;179439249 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/C | None | None | 0.995 | N | 0.683 | 0.364 | 0.580833741332 | gnomAD-4.0.0 | 6.84282E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99567E-07 | 0 | 0 |
| G/S | rs727503564  |
-0.987 | 0.005 | N | 0.294 | 0.103 | None | gnomAD-2.1.1 | 1.43E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.13E-05 | 0 |
| G/S | rs727503564 |
-0.987 | 0.005 | N | 0.294 | 0.103 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 4.78469E-04 |
| G/S | rs727503564 |
-0.987 | 0.005 | N | 0.294 | 0.103 | None | gnomAD-4.0.0 | 1.30159E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.125E-05 | 0 | 1.52591E-05 | 0 | 1.60128E-05 |
| G/V | rs1709389326 |
None | 0.901 | N | 0.675 | 0.277 | 0.611738395503 | gnomAD-4.0.0 | 3.42141E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.49785E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/A | 0.1369 | likely_benign | 0.1287 | benign | -0.405 | Destabilizing | 0.349 | N | 0.436 | neutral | N | 0.394245656 | None | None | N |
| G/C | 0.2248 | likely_benign | 0.2267 | benign | -0.815 | Destabilizing | 0.995 | D | 0.683 | prob.neutral | N | 0.501317193 | None | None | N |
| G/D | 0.5955 | likely_pathogenic | 0.6303 | pathogenic | -0.741 | Destabilizing | 0.722 | D | 0.583 | neutral | N | 0.423680342 | None | None | N |
| G/E | 0.6386 | likely_pathogenic | 0.6683 | pathogenic | -0.889 | Destabilizing | 0.775 | D | 0.591 | neutral | None | None | None | None | N |
| G/F | 0.8179 | likely_pathogenic | 0.8203 | pathogenic | -1.031 | Destabilizing | 0.961 | D | 0.695 | prob.neutral | None | None | None | None | N |
| G/H | 0.6528 | likely_pathogenic | 0.6772 | pathogenic | -0.748 | Destabilizing | 0.989 | D | 0.65 | neutral | None | None | None | None | N |
| G/I | 0.5774 | likely_pathogenic | 0.5525 | ambiguous | -0.438 | Destabilizing | 0.961 | D | 0.679 | prob.neutral | None | None | None | None | N |
| G/K | 0.8495 | likely_pathogenic | 0.8624 | pathogenic | -1.037 | Destabilizing | 0.633 | D | 0.589 | neutral | None | None | None | None | N |
| G/L | 0.5479 | ambiguous | 0.5346 | ambiguous | -0.438 | Destabilizing | 0.923 | D | 0.659 | neutral | None | None | None | None | N |
| G/M | 0.5829 | likely_pathogenic | 0.5791 | pathogenic | -0.461 | Destabilizing | 0.996 | D | 0.683 | prob.neutral | None | None | None | None | N |
| G/N | 0.3999 | ambiguous | 0.412 | ambiguous | -0.59 | Destabilizing | 0.633 | D | 0.549 | neutral | None | None | None | None | N |
| G/P | 0.9825 | likely_pathogenic | 0.9816 | pathogenic | -0.391 | Destabilizing | 0.961 | D | 0.621 | neutral | None | None | None | None | N |
| G/Q | 0.6494 | likely_pathogenic | 0.6589 | pathogenic | -0.867 | Destabilizing | 0.923 | D | 0.634 | neutral | None | None | None | None | N |
| G/R | 0.7123 | likely_pathogenic | 0.725 | pathogenic | -0.575 | Destabilizing | 0.901 | D | 0.629 | neutral | N | 0.431686536 | None | None | N |
| G/S | 0.0871 | likely_benign | 0.0818 | benign | -0.734 | Destabilizing | 0.005 | N | 0.294 | neutral | N | 0.309240115 | None | None | N |
| G/T | 0.1765 | likely_benign | 0.1792 | benign | -0.814 | Destabilizing | 0.633 | D | 0.567 | neutral | None | None | None | None | N |
| G/V | 0.3815 | ambiguous | 0.3628 | ambiguous | -0.391 | Destabilizing | 0.901 | D | 0.675 | neutral | N | 0.468551414 | None | None | N |
| G/W | 0.7511 | likely_pathogenic | 0.7772 | pathogenic | -1.225 | Destabilizing | 0.996 | D | 0.668 | neutral | None | None | None | None | N |
| G/Y | 0.7125 | likely_pathogenic | 0.7209 | pathogenic | -0.879 | Destabilizing | 0.987 | D | 0.693 | 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.