Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19162 | 57709;57710;57711 | chr2:178597598;178597597;178597596 | chr2:179462325;179462324;179462323 |
| N2AB | 17521 | 52786;52787;52788 | chr2:178597598;178597597;178597596 | chr2:179462325;179462324;179462323 |
| N2A | 16594 | 50005;50006;50007 | chr2:178597598;178597597;178597596 | chr2:179462325;179462324;179462323 |
| N2B | 10097 | 30514;30515;30516 | chr2:178597598;178597597;178597596 | chr2:179462325;179462324;179462323 |
| Novex-1 | 10222 | 30889;30890;30891 | chr2:178597598;178597597;178597596 | chr2:179462325;179462324;179462323 |
| Novex-2 | 10289 | 31090;31091;31092 | chr2:178597598;178597597;178597596 | chr2:179462325;179462324;179462323 |
| 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/C | rs751697133  |
-0.208 | 0.97 | N | 0.562 | 0.348 | 0.350964488264 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| S/C | rs751697133 |
-0.208 | 0.97 | N | 0.562 | 0.348 | 0.350964488264 | gnomAD-4.0.0 | 1.59286E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43308E-05 | 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 | 0.1056 | likely_benign | 0.1117 | benign | -0.838 | Destabilizing | 0.002 | N | 0.175 | neutral | N | 0.462211726 | None | None | N |
| S/C | 0.0936 | likely_benign | 0.0957 | benign | -0.814 | Destabilizing | 0.97 | D | 0.562 | neutral | N | 0.476546461 | None | None | N |
| S/D | 0.619 | likely_pathogenic | 0.6528 | pathogenic | -1.866 | Destabilizing | 0.617 | D | 0.524 | neutral | None | None | None | None | N |
| S/E | 0.5986 | likely_pathogenic | 0.5961 | pathogenic | -1.654 | Destabilizing | 0.617 | D | 0.521 | neutral | None | None | None | None | N |
| S/F | 0.1985 | likely_benign | 0.2264 | benign | -0.746 | Destabilizing | 0.896 | D | 0.613 | neutral | N | 0.505482501 | None | None | N |
| S/G | 0.1603 | likely_benign | 0.1704 | benign | -1.223 | Destabilizing | 0.25 | N | 0.519 | neutral | None | None | None | None | N |
| S/H | 0.3175 | likely_benign | 0.3216 | benign | -1.63 | Destabilizing | 0.992 | D | 0.563 | neutral | None | None | None | None | N |
| S/I | 0.1705 | likely_benign | 0.1836 | benign | 0.142 | Stabilizing | 0.739 | D | 0.593 | neutral | None | None | None | None | N |
| S/K | 0.7841 | likely_pathogenic | 0.8083 | pathogenic | -0.282 | Destabilizing | 0.617 | D | 0.514 | neutral | None | None | None | None | N |
| S/L | 0.1256 | likely_benign | 0.1417 | benign | 0.142 | Stabilizing | 0.447 | N | 0.545 | neutral | None | None | None | None | N |
| S/M | 0.1852 | likely_benign | 0.1946 | benign | -0.026 | Destabilizing | 0.92 | D | 0.572 | neutral | None | None | None | None | N |
| S/N | 0.1937 | likely_benign | 0.2034 | benign | -1.126 | Destabilizing | 0.617 | D | 0.536 | neutral | None | None | None | None | N |
| S/P | 0.9639 | likely_pathogenic | 0.9743 | pathogenic | -0.151 | Destabilizing | 0.896 | D | 0.569 | neutral | N | 0.458187329 | None | None | N |
| S/Q | 0.5086 | ambiguous | 0.5084 | ambiguous | -0.836 | Destabilizing | 0.92 | D | 0.545 | neutral | None | None | None | None | N |
| S/R | 0.6688 | likely_pathogenic | 0.6946 | pathogenic | -0.728 | Destabilizing | 0.85 | D | 0.575 | neutral | None | None | None | None | N |
| S/T | 0.068 | likely_benign | 0.0685 | benign | -0.693 | Destabilizing | 0.001 | N | 0.173 | neutral | N | 0.34707528 | None | None | N |
| S/V | 0.1693 | likely_benign | 0.1812 | benign | -0.151 | Destabilizing | 0.447 | N | 0.545 | neutral | None | None | None | None | N |
| S/W | 0.3562 | ambiguous | 0.3864 | ambiguous | -1.094 | Destabilizing | 0.992 | D | 0.691 | prob.neutral | None | None | None | None | N |
| S/Y | 0.1783 | likely_benign | 0.2003 | benign | -0.603 | Destabilizing | 0.896 | D | 0.608 | neutral | N | 0.486550024 | 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.