Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31693 | 95302;95303;95304 | chr2:178546254;178546253;178546252 | chr2:179410981;179410980;179410979 |
| N2AB | 30052 | 90379;90380;90381 | chr2:178546254;178546253;178546252 | chr2:179410981;179410980;179410979 |
| N2A | 29125 | 87598;87599;87600 | chr2:178546254;178546253;178546252 | chr2:179410981;179410980;179410979 |
| N2B | 22628 | 68107;68108;68109 | chr2:178546254;178546253;178546252 | chr2:179410981;179410980;179410979 |
| Novex-1 | 22753 | 68482;68483;68484 | chr2:178546254;178546253;178546252 | chr2:179410981;179410980;179410979 |
| Novex-2 | 22820 | 68683;68684;68685 | chr2:178546254;178546253;178546252 | chr2:179410981;179410980;179410979 |
| 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 | rs2288326  |
-0.051 | 1.0 | N | 0.684 | 0.462 | None | gnomAD-2.1.1 | 1.75095E-04 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.35608E-03 | None | 9.82E-05 | None | 0 | 0 | 0 |
| A/D | rs2288326 |
-0.051 | 1.0 | N | 0.684 | 0.462 | None | gnomAD-3.1.2 | 1.38002E-04 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 4.04624E-03 | None | 0 | 0 | 0 | 0 | 0 |
| A/D | rs2288326 |
-0.051 | 1.0 | N | 0.684 | 0.462 | None | 1000 genomes | 1.39776E-03 | None | None | None | None | I | None | 0 | 0 | None | None | 6.9E-03 | 0 | None | None | None | 0 | None |
| A/D | rs2288326 |
-0.051 | 1.0 | N | 0.684 | 0.462 | None | gnomAD-4.0.0 | 1.95876E-04 | None | None | None | None | I | None | 0 | 0 | None | 0 | 6.79802E-03 | None | 0 | 0 | 8.47948E-07 | 7.68859E-05 | 4.80246E-05 |
| A/T | rs928573760 |
None | 1.0 | N | 0.532 | 0.323 | 0.527809512145 | gnomAD-4.0.0 | 1.16351E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.51927E-05 | None | 0 | 0 | 1.43966E-05 | 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 | 0.6557 | likely_pathogenic | 0.646 | pathogenic | -0.82 | Destabilizing | 1.0 | D | 0.591 | neutral | None | None | None | None | I |
| A/D | 0.6674 | likely_pathogenic | 0.6695 | pathogenic | -0.48 | Destabilizing | 1.0 | D | 0.684 | prob.neutral | N | 0.51218284 | None | None | I |
| A/E | 0.6549 | likely_pathogenic | 0.6659 | pathogenic | -0.629 | Destabilizing | 1.0 | D | 0.581 | neutral | None | None | None | None | I |
| A/F | 0.6055 | likely_pathogenic | 0.6005 | pathogenic | -0.901 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | I |
| A/G | 0.2683 | likely_benign | 0.2655 | benign | -0.203 | Destabilizing | 1.0 | D | 0.34 | neutral | N | 0.490268772 | None | None | I |
| A/H | 0.7396 | likely_pathogenic | 0.7444 | pathogenic | -0.213 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | I |
| A/I | 0.3455 | ambiguous | 0.3241 | benign | -0.389 | Destabilizing | 1.0 | D | 0.573 | neutral | None | None | None | None | I |
| A/K | 0.8237 | likely_pathogenic | 0.8315 | pathogenic | -0.503 | Destabilizing | 1.0 | D | 0.58 | neutral | None | None | None | None | I |
| A/L | 0.3262 | likely_benign | 0.312 | benign | -0.389 | Destabilizing | 1.0 | D | 0.509 | neutral | None | None | None | None | I |
| A/M | 0.4098 | ambiguous | 0.3893 | ambiguous | -0.545 | Destabilizing | 1.0 | D | 0.588 | neutral | None | None | None | None | I |
| A/N | 0.4738 | ambiguous | 0.4569 | ambiguous | -0.201 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | I |
| A/P | 0.2814 | likely_benign | 0.2701 | benign | -0.302 | Destabilizing | 1.0 | D | 0.585 | neutral | N | 0.453097251 | None | None | I |
| A/Q | 0.6302 | likely_pathogenic | 0.6297 | pathogenic | -0.457 | Destabilizing | 1.0 | D | 0.575 | neutral | None | None | None | None | I |
| A/R | 0.7309 | likely_pathogenic | 0.7529 | pathogenic | -0.09 | Destabilizing | 1.0 | D | 0.587 | neutral | None | None | None | None | I |
| A/S | 0.1379 | likely_benign | 0.1319 | benign | -0.388 | Destabilizing | 1.0 | D | 0.395 | neutral | N | 0.438413013 | None | None | I |
| A/T | 0.1461 | likely_benign | 0.1375 | benign | -0.464 | Destabilizing | 1.0 | D | 0.532 | neutral | N | 0.50275528 | None | None | I |
| A/V | 0.1717 | likely_benign | 0.162 | benign | -0.302 | Destabilizing | 1.0 | D | 0.452 | neutral | N | 0.489172694 | None | None | I |
| A/W | 0.9259 | likely_pathogenic | 0.9258 | pathogenic | -1.002 | Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | I |
| A/Y | 0.7425 | likely_pathogenic | 0.7446 | pathogenic | -0.684 | Destabilizing | 1.0 | D | 0.686 | prob.neutral | None | None | None | None | I |
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.