Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28606 | 86041;86042;86043 | chr2:178560316;178560315;178560314 | chr2:179425043;179425042;179425041 |
| N2AB | 26965 | 81118;81119;81120 | chr2:178560316;178560315;178560314 | chr2:179425043;179425042;179425041 |
| N2A | 26038 | 78337;78338;78339 | chr2:178560316;178560315;178560314 | chr2:179425043;179425042;179425041 |
| N2B | 19541 | 58846;58847;58848 | chr2:178560316;178560315;178560314 | chr2:179425043;179425042;179425041 |
| Novex-1 | 19666 | 59221;59222;59223 | chr2:178560316;178560315;178560314 | chr2:179425043;179425042;179425041 |
| Novex-2 | 19733 | 59422;59423;59424 | chr2:178560316;178560315;178560314 | chr2:179425043;179425042;179425041 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs748945937  |
0.144 | 0.986 | N | 0.644 | 0.307 | 0.411133732114 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.65837E-04 |
| Y/F | rs748945937 |
-0.004 | 0.008 | N | 0.263 | 0.086 | 0.197625483188 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| Y/F | rs748945937 |
-0.004 | 0.008 | N | 0.263 | 0.086 | 0.197625483188 | gnomAD-4.0.0 | 3.1826E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.86549E-05 | 0 |
| Y/H | rs757029350 |
0.35 | 0.983 | N | 0.602 | 0.255 | 0.285698343383 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| Y/H | rs757029350 |
0.35 | 0.983 | N | 0.602 | 0.255 | 0.285698343383 | gnomAD-4.0.0 | 6.36507E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.14327E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.4249 | ambiguous | 0.405 | ambiguous | -0.913 | Destabilizing | 0.011 | N | 0.322 | neutral | None | None | None | None | N |
| Y/C | 0.128 | likely_benign | 0.1223 | benign | -0.114 | Destabilizing | 0.986 | D | 0.644 | neutral | N | 0.467089976 | None | None | N |
| Y/D | 0.34 | ambiguous | 0.315 | benign | 0.787 | Stabilizing | 0.949 | D | 0.635 | neutral | N | 0.393034935 | None | None | N |
| Y/E | 0.645 | likely_pathogenic | 0.6245 | pathogenic | 0.794 | Stabilizing | 0.923 | D | 0.594 | neutral | None | None | None | None | N |
| Y/F | 0.1223 | likely_benign | 0.12 | benign | -0.311 | Destabilizing | 0.008 | N | 0.263 | neutral | N | 0.422107048 | None | None | N |
| Y/G | 0.3219 | likely_benign | 0.3063 | benign | -1.126 | Destabilizing | 0.633 | D | 0.507 | neutral | None | None | None | None | N |
| Y/H | 0.2295 | likely_benign | 0.2133 | benign | 0.109 | Stabilizing | 0.983 | D | 0.602 | neutral | N | 0.41800795 | None | None | N |
| Y/I | 0.5015 | ambiguous | 0.4959 | ambiguous | -0.348 | Destabilizing | 0.858 | D | 0.537 | neutral | None | None | None | None | N |
| Y/K | 0.5318 | ambiguous | 0.5191 | ambiguous | -0.081 | Destabilizing | 0.923 | D | 0.61 | neutral | None | None | None | None | N |
| Y/L | 0.4077 | ambiguous | 0.4063 | ambiguous | -0.348 | Destabilizing | 0.633 | D | 0.525 | neutral | None | None | None | None | N |
| Y/M | 0.5613 | ambiguous | 0.561 | ambiguous | -0.269 | Destabilizing | 0.989 | D | 0.615 | neutral | None | None | None | None | N |
| Y/N | 0.1919 | likely_benign | 0.1865 | benign | -0.35 | Destabilizing | 0.949 | D | 0.625 | neutral | N | 0.365829691 | None | None | N |
| Y/P | 0.5836 | likely_pathogenic | 0.5493 | ambiguous | -0.519 | Destabilizing | 0.961 | D | 0.639 | neutral | None | None | None | None | N |
| Y/Q | 0.4865 | ambiguous | 0.461 | ambiguous | -0.261 | Destabilizing | 0.961 | D | 0.609 | neutral | None | None | None | None | N |
| Y/R | 0.3512 | ambiguous | 0.3401 | ambiguous | 0.176 | Stabilizing | 0.961 | D | 0.628 | neutral | None | None | None | None | N |
| Y/S | 0.1738 | likely_benign | 0.1663 | benign | -0.8 | Destabilizing | 0.565 | D | 0.491 | neutral | N | 0.347377216 | None | None | N |
| Y/T | 0.3048 | likely_benign | 0.2969 | benign | -0.703 | Destabilizing | 0.923 | D | 0.508 | neutral | None | None | None | None | N |
| Y/V | 0.379 | ambiguous | 0.3739 | ambiguous | -0.519 | Destabilizing | 0.633 | D | 0.55 | neutral | None | None | None | None | N |
| Y/W | 0.381 | ambiguous | 0.3724 | ambiguous | -0.326 | Destabilizing | 0.996 | D | 0.599 | 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.