Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14003 | 42232;42233;42234 | chr2:178635182;178635181;178635180 | chr2:179499909;179499908;179499907 |
| N2AB | 12362 | 37309;37310;37311 | chr2:178635182;178635181;178635180 | chr2:179499909;179499908;179499907 |
| N2A | 11435 | 34528;34529;34530 | chr2:178635182;178635181;178635180 | chr2:179499909;179499908;179499907 |
| N2B | 4938 | 15037;15038;15039 | chr2:178635182;178635181;178635180 | chr2:179499909;179499908;179499907 |
| Novex-1 | 5063 | 15412;15413;15414 | chr2:178635182;178635181;178635180 | chr2:179499909;179499908;179499907 |
| Novex-2 | 5130 | 15613;15614;15615 | chr2:178635182;178635181;178635180 | chr2:179499909;179499908;179499907 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs767585297  |
-0.723 | 0.437 | N | 0.338 | 0.046 | None | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 6.47E-05 | 2.91E-05 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| L/F | rs767585297 |
-0.723 | 0.437 | N | 0.338 | 0.046 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07469E-04 | 0 |
| L/F | rs767585297 |
-0.723 | 0.437 | N | 0.338 | 0.046 | None | gnomAD-4.0.0 | 6.41248E-06 | None | None | None | None | N | None | 1.69279E-05 | 1.69848E-05 | None | 0 | 0 | None | 0 | 0 | 2.39519E-06 | 1.3425E-05 | 2.84787E-05 |
| L/P | rs1162691488 |
-0.547 | 0.828 | N | 0.574 | 0.269 | 0.415055319159 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.29E-05 | None | 0 | 0 | 0 |
| L/P | rs1162691488 |
-0.547 | 0.828 | N | 0.574 | 0.269 | 0.415055319159 | gnomAD-4.0.0 | 2.05369E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 3.48367E-05 | 0 |
| L/R | None | None | 0.612 | N | 0.506 | 0.198 | 0.398133443147 | gnomAD-4.0.0 | 6.84563E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.73732E-04 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.4181 | ambiguous | 0.2468 | benign | -0.911 | Destabilizing | 0.057 | N | 0.287 | neutral | None | None | None | None | N |
| L/C | 0.8017 | likely_pathogenic | 0.7225 | pathogenic | -0.621 | Destabilizing | 0.887 | D | 0.328 | neutral | None | None | None | None | N |
| L/D | 0.743 | likely_pathogenic | 0.5607 | ambiguous | -0.411 | Destabilizing | 0.676 | D | 0.569 | neutral | None | None | None | None | N |
| L/E | 0.4457 | ambiguous | 0.2975 | benign | -0.477 | Destabilizing | 0.676 | D | 0.515 | neutral | None | None | None | None | N |
| L/F | 0.3393 | likely_benign | 0.2257 | benign | -0.714 | Destabilizing | 0.437 | N | 0.338 | neutral | N | 0.436832397 | None | None | N |
| L/G | 0.8072 | likely_pathogenic | 0.6576 | pathogenic | -1.126 | Destabilizing | 0.676 | D | 0.497 | neutral | None | None | None | None | N |
| L/H | 0.6064 | likely_pathogenic | 0.4078 | ambiguous | -0.35 | Destabilizing | 0.948 | D | 0.514 | neutral | N | 0.437409307 | None | None | N |
| L/I | 0.1069 | likely_benign | 0.0838 | benign | -0.443 | Destabilizing | None | N | 0.053 | neutral | N | 0.394806952 | None | None | N |
| L/K | 0.6161 | likely_pathogenic | 0.4479 | ambiguous | -0.608 | Destabilizing | 0.676 | D | 0.452 | neutral | None | None | None | None | N |
| L/M | 0.1502 | likely_benign | 0.1165 | benign | -0.459 | Destabilizing | 0.507 | D | 0.487 | neutral | None | None | None | None | N |
| L/N | 0.4619 | ambiguous | 0.3032 | benign | -0.349 | Destabilizing | 0.864 | D | 0.536 | neutral | None | None | None | None | N |
| L/P | 0.4426 | ambiguous | 0.286 | benign | -0.566 | Destabilizing | 0.828 | D | 0.574 | neutral | N | 0.387330434 | None | None | N |
| L/Q | 0.4012 | ambiguous | 0.2386 | benign | -0.572 | Destabilizing | 0.864 | D | 0.467 | neutral | None | None | None | None | N |
| L/R | 0.6287 | likely_pathogenic | 0.442 | ambiguous | -0.015 | Destabilizing | 0.612 | D | 0.506 | neutral | N | 0.435725285 | None | None | N |
| L/S | 0.5653 | likely_pathogenic | 0.3299 | benign | -0.832 | Destabilizing | 0.227 | N | 0.443 | neutral | None | None | None | None | N |
| L/T | 0.2723 | likely_benign | 0.1672 | benign | -0.792 | Destabilizing | 0.227 | N | 0.329 | neutral | None | None | None | None | N |
| L/V | 0.115 | likely_benign | 0.0842 | benign | -0.566 | Destabilizing | None | N | 0.058 | neutral | N | 0.358761722 | None | None | N |
| L/W | 0.6191 | likely_pathogenic | 0.4959 | ambiguous | -0.733 | Destabilizing | 0.96 | D | 0.555 | neutral | None | None | None | None | N |
| L/Y | 0.6023 | likely_pathogenic | 0.4731 | ambiguous | -0.511 | Destabilizing | 0.676 | D | 0.402 | 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.