Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35180 | 105763;105764;105765 | chr2:178531077;178531076;178531075 | chr2:179395804;179395803;179395802 |
| N2AB | 33539 | 100840;100841;100842 | chr2:178531077;178531076;178531075 | chr2:179395804;179395803;179395802 |
| N2A | 32612 | 98059;98060;98061 | chr2:178531077;178531076;178531075 | chr2:179395804;179395803;179395802 |
| N2B | 26115 | 78568;78569;78570 | chr2:178531077;178531076;178531075 | chr2:179395804;179395803;179395802 |
| Novex-1 | 26240 | 78943;78944;78945 | chr2:178531077;178531076;178531075 | chr2:179395804;179395803;179395802 |
| Novex-2 | 26307 | 79144;79145;79146 | chr2:178531077;178531076;178531075 | chr2:179395804;179395803;179395802 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs1473790126  |
-0.342 | None | N | 0.143 | 0.125 | 0.12205267543 | gnomAD-2.1.1 | 4.01E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.85E-06 | 0 |
| T/A | rs1473790126 |
-0.342 | None | N | 0.143 | 0.125 | 0.12205267543 | gnomAD-4.0.0 | 1.36827E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79878E-06 | 0 | 0 |
| T/K | rs1575225765 |
None | 0.052 | N | 0.346 | 0.218 | 0.337378238328 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0876 | likely_benign | 0.1112 | benign | -0.359 | Destabilizing | None | N | 0.143 | neutral | N | 0.519071527 | None | None | N |
| T/C | 0.6292 | likely_pathogenic | 0.6916 | pathogenic | -0.275 | Destabilizing | 0.796 | D | 0.449 | neutral | None | None | None | None | N |
| T/D | 0.3766 | ambiguous | 0.4299 | ambiguous | 0.232 | Stabilizing | 0.203 | N | 0.34 | neutral | None | None | None | None | N |
| T/E | 0.3234 | likely_benign | 0.3771 | ambiguous | 0.15 | Stabilizing | 0.068 | N | 0.332 | neutral | None | None | None | None | N |
| T/F | 0.4483 | ambiguous | 0.4884 | ambiguous | -0.941 | Destabilizing | 0.508 | D | 0.535 | neutral | None | None | None | None | N |
| T/G | 0.2105 | likely_benign | 0.2461 | benign | -0.463 | Destabilizing | 0.068 | N | 0.404 | neutral | None | None | None | None | N |
| T/H | 0.3971 | ambiguous | 0.4243 | ambiguous | -0.766 | Destabilizing | 0.796 | D | 0.549 | neutral | None | None | None | None | N |
| T/I | 0.4236 | ambiguous | 0.4798 | ambiguous | -0.208 | Destabilizing | 0.278 | N | 0.407 | neutral | N | 0.518052806 | None | None | N |
| T/K | 0.2959 | likely_benign | 0.319 | benign | -0.306 | Destabilizing | 0.052 | N | 0.346 | neutral | N | 0.510238613 | None | None | N |
| T/L | 0.1878 | likely_benign | 0.2113 | benign | -0.208 | Destabilizing | 0.068 | N | 0.355 | neutral | None | None | None | None | N |
| T/M | 0.149 | likely_benign | 0.1711 | benign | -0.043 | Destabilizing | 0.796 | D | 0.423 | neutral | None | None | None | None | N |
| T/N | 0.1535 | likely_benign | 0.1651 | benign | -0.118 | Destabilizing | 0.203 | N | 0.291 | neutral | None | None | None | None | N |
| T/P | 0.3692 | ambiguous | 0.4571 | ambiguous | -0.231 | Destabilizing | 0.278 | N | 0.411 | neutral | D | 0.536638567 | None | None | N |
| T/Q | 0.2794 | likely_benign | 0.3061 | benign | -0.329 | Destabilizing | 0.338 | N | 0.405 | neutral | None | None | None | None | N |
| T/R | 0.2232 | likely_benign | 0.254 | benign | -0.063 | Destabilizing | 0.278 | N | 0.411 | neutral | N | 0.440784101 | None | None | N |
| T/S | 0.1004 | likely_benign | 0.1146 | benign | -0.321 | Destabilizing | None | N | 0.139 | neutral | N | 0.469450783 | None | None | N |
| T/V | 0.2676 | likely_benign | 0.302 | benign | -0.231 | Destabilizing | 0.068 | N | 0.3 | neutral | None | None | None | None | N |
| T/W | 0.7488 | likely_pathogenic | 0.7784 | pathogenic | -0.966 | Destabilizing | 0.922 | D | 0.601 | neutral | None | None | None | None | N |
| T/Y | 0.5191 | ambiguous | 0.5597 | ambiguous | -0.667 | Destabilizing | 0.508 | D | 0.527 | 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.