Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25138 | 75637;75638;75639 | chr2:178570720;178570719;178570718 | chr2:179435447;179435446;179435445 |
| N2AB | 23497 | 70714;70715;70716 | chr2:178570720;178570719;178570718 | chr2:179435447;179435446;179435445 |
| N2A | 22570 | 67933;67934;67935 | chr2:178570720;178570719;178570718 | chr2:179435447;179435446;179435445 |
| N2B | 16073 | 48442;48443;48444 | chr2:178570720;178570719;178570718 | chr2:179435447;179435446;179435445 |
| Novex-1 | 16198 | 48817;48818;48819 | chr2:178570720;178570719;178570718 | chr2:179435447;179435446;179435445 |
| Novex-2 | 16265 | 49018;49019;49020 | chr2:178570720;178570719;178570718 | chr2:179435447;179435446;179435445 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/Q | rs1392761642  |
0.227 | 0.978 | N | 0.678 | 0.487 | 0.355242300401 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| K/Q | rs1392761642 |
0.227 | 0.978 | N | 0.678 | 0.487 | 0.355242300401 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-06 | 0 | 0 |
| K/R | rs376597438 |
0.08 | 0.085 | N | 0.351 | 0.18 | None | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| K/R | rs376597438 |
0.08 | 0.085 | N | 0.351 | 0.18 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| K/R | rs376597438 |
0.08 | 0.085 | N | 0.351 | 0.18 | None | gnomAD-4.0.0 | 2.54095E-05 | None | None | None | None | I | None | 1.33326E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 3.30616E-05 | 0 | 1.60087E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.8938 | likely_pathogenic | 0.8815 | pathogenic | 0.039 | Stabilizing | 0.944 | D | 0.629 | neutral | None | None | None | None | I |
| K/C | 0.9053 | likely_pathogenic | 0.8879 | pathogenic | -0.445 | Destabilizing | 0.999 | D | 0.779 | deleterious | None | None | None | None | I |
| K/D | 0.9783 | likely_pathogenic | 0.9748 | pathogenic | -0.306 | Destabilizing | 0.983 | D | 0.695 | prob.neutral | None | None | None | None | I |
| K/E | 0.7863 | likely_pathogenic | 0.7458 | pathogenic | -0.315 | Destabilizing | 0.928 | D | 0.577 | neutral | N | 0.501619129 | None | None | I |
| K/F | 0.9407 | likely_pathogenic | 0.9343 | pathogenic | -0.287 | Destabilizing | 0.999 | D | 0.739 | prob.delet. | None | None | None | None | I |
| K/G | 0.9398 | likely_pathogenic | 0.9307 | pathogenic | -0.094 | Destabilizing | 0.983 | D | 0.635 | neutral | None | None | None | None | I |
| K/H | 0.5946 | likely_pathogenic | 0.5696 | pathogenic | -0.178 | Destabilizing | 0.998 | D | 0.695 | prob.neutral | None | None | None | None | I |
| K/I | 0.6876 | likely_pathogenic | 0.6454 | pathogenic | 0.306 | Stabilizing | 0.989 | D | 0.743 | deleterious | N | 0.488467941 | None | None | I |
| K/L | 0.6928 | likely_pathogenic | 0.6689 | pathogenic | 0.306 | Stabilizing | 0.983 | D | 0.635 | neutral | None | None | None | None | I |
| K/M | 0.5471 | ambiguous | 0.5246 | ambiguous | -0.099 | Destabilizing | 0.999 | D | 0.697 | prob.neutral | None | None | None | None | I |
| K/N | 0.8979 | likely_pathogenic | 0.8856 | pathogenic | 0.002 | Stabilizing | 0.978 | D | 0.687 | prob.neutral | D | 0.525477424 | None | None | I |
| K/P | 0.9941 | likely_pathogenic | 0.9917 | pathogenic | 0.24 | Stabilizing | 0.997 | D | 0.693 | prob.neutral | None | None | None | None | I |
| K/Q | 0.413 | ambiguous | 0.3696 | ambiguous | -0.132 | Destabilizing | 0.978 | D | 0.678 | prob.neutral | N | 0.499455398 | None | None | I |
| K/R | 0.1238 | likely_benign | 0.1216 | benign | -0.097 | Destabilizing | 0.085 | N | 0.351 | neutral | N | 0.483612159 | None | None | I |
| K/S | 0.8986 | likely_pathogenic | 0.8867 | pathogenic | -0.348 | Destabilizing | 0.944 | D | 0.661 | neutral | None | None | None | None | I |
| K/T | 0.6836 | likely_pathogenic | 0.6423 | pathogenic | -0.241 | Destabilizing | 0.978 | D | 0.642 | neutral | D | 0.535096985 | None | None | I |
| K/V | 0.6944 | likely_pathogenic | 0.6649 | pathogenic | 0.24 | Stabilizing | 0.992 | D | 0.715 | prob.delet. | None | None | None | None | I |
| K/W | 0.944 | likely_pathogenic | 0.9375 | pathogenic | -0.4 | Destabilizing | 0.999 | D | 0.779 | deleterious | None | None | None | None | I |
| K/Y | 0.8746 | likely_pathogenic | 0.8603 | pathogenic | -0.046 | Destabilizing | 0.997 | D | 0.741 | deleterious | None | None | None | None | I |
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.