Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23614 | 71065;71066;71067 | chr2:178575292;178575291;178575290 | chr2:179440019;179440018;179440017 |
| N2AB | 21973 | 66142;66143;66144 | chr2:178575292;178575291;178575290 | chr2:179440019;179440018;179440017 |
| N2A | 21046 | 63361;63362;63363 | chr2:178575292;178575291;178575290 | chr2:179440019;179440018;179440017 |
| N2B | 14549 | 43870;43871;43872 | chr2:178575292;178575291;178575290 | chr2:179440019;179440018;179440017 |
| Novex-1 | 14674 | 44245;44246;44247 | chr2:178575292;178575291;178575290 | chr2:179440019;179440018;179440017 |
| Novex-2 | 14741 | 44446;44447;44448 | chr2:178575292;178575291;178575290 | chr2:179440019;179440018;179440017 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/G | None | None | 0.099 | N | 0.443 | 0.142 | 0.0920862733494 | gnomAD-4.0.0 | 1.20034E-06 | None | None | None | None | N | None | 6.33473E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/N | None | None | 0.841 | D | 0.716 | 0.306 | 0.301455362545 | gnomAD-4.0.0 | 2.0531E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69871E-06 | 0 | 0 |
| S/T | rs1237254642  |
-1.05 | 0.636 | D | 0.702 | 0.371 | 0.253726318573 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| S/T | rs1237254642 |
-1.05 | 0.636 | D | 0.702 | 0.371 | 0.253726318573 | gnomAD-4.0.0 | 1.36873E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79914E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.6005 | likely_pathogenic | 0.5968 | pathogenic | -0.687 | Destabilizing | 0.702 | D | 0.682 | prob.neutral | None | None | None | None | N |
| S/C | 0.8409 | likely_pathogenic | 0.8552 | pathogenic | -0.641 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | D | 0.536445652 | None | None | N |
| S/D | 0.9883 | likely_pathogenic | 0.9878 | pathogenic | -1.145 | Destabilizing | 0.984 | D | 0.729 | prob.delet. | None | None | None | None | N |
| S/E | 0.9953 | likely_pathogenic | 0.9954 | pathogenic | -1.112 | Destabilizing | 0.994 | D | 0.744 | deleterious | None | None | None | None | N |
| S/F | 0.9955 | likely_pathogenic | 0.9957 | pathogenic | -0.677 | Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | N |
| S/G | 0.2197 | likely_benign | 0.2077 | benign | -0.974 | Destabilizing | 0.099 | N | 0.443 | neutral | N | 0.468156264 | None | None | N |
| S/H | 0.9915 | likely_pathogenic | 0.9915 | pathogenic | -1.456 | Destabilizing | 1.0 | D | 0.732 | prob.delet. | None | None | None | None | N |
| S/I | 0.9931 | likely_pathogenic | 0.9945 | pathogenic | -0.02 | Destabilizing | 1.0 | D | 0.803 | deleterious | D | 0.536192162 | None | None | N |
| S/K | 0.9988 | likely_pathogenic | 0.9989 | pathogenic | -1.004 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| S/L | 0.9706 | likely_pathogenic | 0.9759 | pathogenic | -0.02 | Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | N |
| S/M | 0.9823 | likely_pathogenic | 0.9848 | pathogenic | 0.232 | Stabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| S/N | 0.9671 | likely_pathogenic | 0.9672 | pathogenic | -1.125 | Destabilizing | 0.841 | D | 0.716 | prob.delet. | D | 0.546952583 | None | None | N |
| S/P | 0.9953 | likely_pathogenic | 0.9961 | pathogenic | -0.208 | Destabilizing | 0.999 | D | 0.769 | deleterious | None | None | None | None | N |
| S/Q | 0.9942 | likely_pathogenic | 0.9941 | pathogenic | -1.246 | Destabilizing | 1.0 | D | 0.766 | deleterious | None | None | None | None | N |
| S/R | 0.9978 | likely_pathogenic | 0.9979 | pathogenic | -0.888 | Destabilizing | 1.0 | D | 0.769 | deleterious | D | 0.529101818 | None | None | N |
| S/T | 0.8332 | likely_pathogenic | 0.8573 | pathogenic | -0.99 | Destabilizing | 0.636 | D | 0.702 | prob.neutral | D | 0.534417735 | None | None | N |
| S/V | 0.9896 | likely_pathogenic | 0.9917 | pathogenic | -0.208 | Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | N |
| S/W | 0.9948 | likely_pathogenic | 0.9953 | pathogenic | -0.745 | Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | N |
| S/Y | 0.9911 | likely_pathogenic | 0.9921 | pathogenic | -0.461 | Destabilizing | 1.0 | D | 0.806 | deleterious | 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.