Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29851 | 89776;89777;89778 | chr2:178553349;178553348;178553347 | chr2:179418076;179418075;179418074 |
| N2AB | 28210 | 84853;84854;84855 | chr2:178553349;178553348;178553347 | chr2:179418076;179418075;179418074 |
| N2A | 27283 | 82072;82073;82074 | chr2:178553349;178553348;178553347 | chr2:179418076;179418075;179418074 |
| N2B | 20786 | 62581;62582;62583 | chr2:178553349;178553348;178553347 | chr2:179418076;179418075;179418074 |
| Novex-1 | 20911 | 62956;62957;62958 | chr2:178553349;178553348;178553347 | chr2:179418076;179418075;179418074 |
| Novex-2 | 20978 | 63157;63158;63159 | chr2:178553349;178553348;178553347 | chr2:179418076;179418075;179418074 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/D | rs774885355  |
-1.432 | 1.0 | N | 0.676 | 0.623 | 0.806978627759 | gnomAD-2.1.1 | 8.27E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.59E-05 | None | 0 | 0 | 0 |
| A/D | rs774885355 |
-1.432 | 1.0 | N | 0.676 | 0.623 | 0.806978627759 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/D | rs774885355 |
-1.432 | 1.0 | N | 0.676 | 0.623 | 0.806978627759 | gnomAD-4.0.0 | 8.74292E-06 | None | None | None | None | N | None | 0 | 1.66867E-05 | None | 0 | 0 | None | 0 | 0 | 2.55085E-06 | 9.90426E-05 | 1.60705E-05 |
| A/V | rs774885355 |
None | 0.884 | N | 0.39 | 0.166 | 0.415313616471 | gnomAD-4.0.0 | 5.52057E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.21983E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.4694 | ambiguous | 0.4473 | ambiguous | -0.953 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| A/D | 0.9456 | likely_pathogenic | 0.9134 | pathogenic | -1.648 | Destabilizing | 1.0 | D | 0.676 | prob.neutral | N | 0.516780094 | None | None | N |
| A/E | 0.8357 | likely_pathogenic | 0.7858 | pathogenic | -1.606 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| A/F | 0.6795 | likely_pathogenic | 0.6609 | pathogenic | -0.9 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| A/G | 0.3459 | ambiguous | 0.3046 | benign | -1.346 | Destabilizing | 0.999 | D | 0.58 | neutral | D | 0.531291462 | None | None | N |
| A/H | 0.867 | likely_pathogenic | 0.8496 | pathogenic | -1.631 | Destabilizing | 1.0 | D | 0.649 | neutral | None | None | None | None | N |
| A/I | 0.4187 | ambiguous | 0.3681 | ambiguous | -0.232 | Destabilizing | 0.994 | D | 0.651 | neutral | None | None | None | None | N |
| A/K | 0.8325 | likely_pathogenic | 0.8016 | pathogenic | -1.492 | Destabilizing | 1.0 | D | 0.708 | prob.delet. | None | None | None | None | N |
| A/L | 0.3815 | ambiguous | 0.364 | ambiguous | -0.232 | Destabilizing | 0.994 | D | 0.554 | neutral | None | None | None | None | N |
| A/M | 0.5019 | ambiguous | 0.4582 | ambiguous | -0.202 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| A/N | 0.8688 | likely_pathogenic | 0.8296 | pathogenic | -1.343 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| A/P | 0.9404 | likely_pathogenic | 0.9049 | pathogenic | -0.45 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | N | 0.498422349 | None | None | N |
| A/Q | 0.7447 | likely_pathogenic | 0.7156 | pathogenic | -1.393 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| A/R | 0.7361 | likely_pathogenic | 0.7137 | pathogenic | -1.213 | Destabilizing | 1.0 | D | 0.714 | prob.delet. | None | None | None | None | N |
| A/S | 0.2214 | likely_benign | 0.1966 | benign | -1.695 | Destabilizing | 0.998 | D | 0.592 | neutral | N | 0.486305575 | None | None | N |
| A/T | 0.1734 | likely_benign | 0.1402 | benign | -1.557 | Destabilizing | 0.996 | D | 0.638 | neutral | N | 0.521805187 | None | None | N |
| A/V | 0.1709 | likely_benign | 0.143 | benign | -0.45 | Destabilizing | 0.884 | D | 0.39 | neutral | N | 0.362933819 | None | None | N |
| A/W | 0.9399 | likely_pathogenic | 0.9344 | pathogenic | -1.419 | Destabilizing | 1.0 | D | 0.653 | neutral | None | None | None | None | N |
| A/Y | 0.8213 | likely_pathogenic | 0.805 | pathogenic | -0.963 | Destabilizing | 1.0 | D | 0.701 | prob.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.