Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25865 | 77818;77819;77820 | chr2:178568539;178568538;178568537 | chr2:179433266;179433265;179433264 |
| N2AB | 24224 | 72895;72896;72897 | chr2:178568539;178568538;178568537 | chr2:179433266;179433265;179433264 |
| N2A | 23297 | 70114;70115;70116 | chr2:178568539;178568538;178568537 | chr2:179433266;179433265;179433264 |
| N2B | 16800 | 50623;50624;50625 | chr2:178568539;178568538;178568537 | chr2:179433266;179433265;179433264 |
| Novex-1 | 16925 | 50998;50999;51000 | chr2:178568539;178568538;178568537 | chr2:179433266;179433265;179433264 |
| Novex-2 | 16992 | 51199;51200;51201 | chr2:178568539;178568538;178568537 | chr2:179433266;179433265;179433264 |
| 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/D | rs756930121  |
-0.047 | 0.001 | N | 0.353 | 0.139 | 0.218112801441 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.58E-05 | None | 3.27E-05 | None | 0 | 0 | 0 |
| G/D | rs756930121 |
-0.047 | 0.001 | N | 0.353 | 0.139 | 0.218112801441 | gnomAD-4.0.0 | 3.18384E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43295E-05 | 3.02645E-05 |
| G/S | None | None | 0.001 | N | 0.239 | 0.09 | 0.126345400529 | gnomAD-4.0.0 | 3.42169E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.49807E-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 | 0.079 | likely_benign | 0.0756 | benign | -0.632 | Destabilizing | 0.004 | N | 0.259 | neutral | N | 0.407130101 | None | None | N |
| G/C | 0.1081 | likely_benign | 0.108 | benign | -0.969 | Destabilizing | 0.883 | D | 0.761 | deleterious | N | 0.491150513 | None | None | N |
| G/D | 0.3952 | ambiguous | 0.4154 | ambiguous | -0.658 | Destabilizing | 0.001 | N | 0.353 | neutral | N | 0.516703225 | None | None | N |
| G/E | 0.3183 | likely_benign | 0.3527 | ambiguous | -0.734 | Destabilizing | 0.157 | N | 0.633 | neutral | None | None | None | None | N |
| G/F | 0.4352 | ambiguous | 0.4565 | ambiguous | -1.062 | Destabilizing | 0.726 | D | 0.777 | deleterious | None | None | None | None | N |
| G/H | 0.3136 | likely_benign | 0.3349 | benign | -1.156 | Destabilizing | 0.909 | D | 0.724 | prob.delet. | None | None | None | None | N |
| G/I | 0.2033 | likely_benign | 0.2218 | benign | -0.328 | Destabilizing | 0.567 | D | 0.771 | deleterious | None | None | None | None | N |
| G/K | 0.3778 | ambiguous | 0.4072 | ambiguous | -1.003 | Destabilizing | 0.396 | N | 0.655 | neutral | None | None | None | None | N |
| G/L | 0.3233 | likely_benign | 0.3368 | benign | -0.328 | Destabilizing | 0.567 | D | 0.691 | prob.neutral | None | None | None | None | N |
| G/M | 0.3229 | likely_benign | 0.3344 | benign | -0.352 | Destabilizing | 0.968 | D | 0.76 | deleterious | None | None | None | None | N |
| G/N | 0.2932 | likely_benign | 0.294 | benign | -0.675 | Destabilizing | 0.157 | N | 0.522 | neutral | None | None | None | None | N |
| G/P | 0.8984 | likely_pathogenic | 0.9182 | pathogenic | -0.388 | Destabilizing | 0.567 | D | 0.723 | prob.delet. | None | None | None | None | N |
| G/Q | 0.2849 | likely_benign | 0.3038 | benign | -0.855 | Destabilizing | 0.567 | D | 0.731 | prob.delet. | None | None | None | None | N |
| G/R | 0.235 | likely_benign | 0.2605 | benign | -0.724 | Destabilizing | 0.497 | N | 0.731 | prob.delet. | N | 0.502600564 | None | None | N |
| G/S | 0.0693 | likely_benign | 0.0645 | benign | -0.993 | Destabilizing | 0.001 | N | 0.239 | neutral | N | 0.417037663 | None | None | N |
| G/T | 0.0999 | likely_benign | 0.1049 | benign | -0.974 | Destabilizing | 0.157 | N | 0.634 | neutral | None | None | None | None | N |
| G/V | 0.1588 | likely_benign | 0.167 | benign | -0.388 | Destabilizing | 0.497 | N | 0.694 | prob.neutral | N | 0.460849942 | None | None | N |
| G/W | 0.4032 | ambiguous | 0.4324 | ambiguous | -1.352 | Destabilizing | 0.968 | D | 0.727 | prob.delet. | None | None | None | None | N |
| G/Y | 0.3353 | likely_benign | 0.3512 | ambiguous | -0.933 | Destabilizing | 0.726 | D | 0.768 | 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.