Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23585 | 70978;70979;70980 | chr2:178575379;178575378;178575377 | chr2:179440106;179440105;179440104 |
| N2AB | 21944 | 66055;66056;66057 | chr2:178575379;178575378;178575377 | chr2:179440106;179440105;179440104 |
| N2A | 21017 | 63274;63275;63276 | chr2:178575379;178575378;178575377 | chr2:179440106;179440105;179440104 |
| N2B | 14520 | 43783;43784;43785 | chr2:178575379;178575378;178575377 | chr2:179440106;179440105;179440104 |
| Novex-1 | 14645 | 44158;44159;44160 | chr2:178575379;178575378;178575377 | chr2:179440106;179440105;179440104 |
| Novex-2 | 14712 | 44359;44360;44361 | chr2:178575379;178575378;178575377 | chr2:179440106;179440105;179440104 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | None | None | 0.861 | N | 0.415 | 0.314 | 0.639809546828 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 6.33473E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/M | rs754040141  |
-0.394 | 0.997 | N | 0.494 | 0.351 | 0.635224905023 | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | I | None | 0 | 5.8E-05 | None | 1.99084E-04 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| V/M | rs754040141 |
-0.394 | 0.997 | N | 0.494 | 0.351 | 0.635224905023 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.78927E-04 |
| V/M | rs754040141 |
-0.394 | 0.997 | N | 0.494 | 0.351 | 0.635224905023 | gnomAD-4.0.0 | 1.05363E-05 | None | None | None | None | I | None | 2.67023E-05 | 1.00023E-04 | None | 0 | 0 | None | 0 | 0 | 1.69538E-06 | 3.29366E-05 | 6.40574E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2847 | likely_benign | 0.2678 | benign | -1.308 | Destabilizing | 0.861 | D | 0.415 | neutral | N | 0.482115979 | None | None | I |
| V/C | 0.7808 | likely_pathogenic | 0.7938 | pathogenic | -0.849 | Destabilizing | 0.126 | N | 0.383 | neutral | None | None | None | None | I |
| V/D | 0.7676 | likely_pathogenic | 0.7485 | pathogenic | -0.587 | Destabilizing | 0.999 | D | 0.582 | neutral | None | None | None | None | I |
| V/E | 0.5714 | likely_pathogenic | 0.5685 | pathogenic | -0.492 | Destabilizing | 0.992 | D | 0.546 | neutral | N | 0.490331959 | None | None | I |
| V/F | 0.3847 | ambiguous | 0.3367 | benign | -0.752 | Destabilizing | 0.992 | D | 0.489 | neutral | None | None | None | None | I |
| V/G | 0.3842 | ambiguous | 0.3559 | ambiguous | -1.721 | Destabilizing | 0.997 | D | 0.553 | neutral | N | 0.471506915 | None | None | I |
| V/H | 0.8321 | likely_pathogenic | 0.8325 | pathogenic | -1.227 | Destabilizing | 1.0 | D | 0.573 | neutral | None | None | None | None | I |
| V/I | 0.105 | likely_benign | 0.103 | benign | -0.243 | Destabilizing | 0.017 | N | 0.147 | neutral | None | None | None | None | I |
| V/K | 0.7135 | likely_pathogenic | 0.715 | pathogenic | -0.807 | Destabilizing | 0.997 | D | 0.532 | neutral | None | None | None | None | I |
| V/L | 0.3169 | likely_benign | 0.3017 | benign | -0.243 | Destabilizing | 0.008 | N | 0.155 | neutral | N | 0.511150185 | None | None | I |
| V/M | 0.2197 | likely_benign | 0.2021 | benign | -0.294 | Destabilizing | 0.997 | D | 0.494 | neutral | N | 0.501260645 | None | None | I |
| V/N | 0.5587 | ambiguous | 0.5628 | ambiguous | -0.752 | Destabilizing | 0.982 | D | 0.583 | neutral | None | None | None | None | I |
| V/P | 0.9436 | likely_pathogenic | 0.9318 | pathogenic | -0.563 | Destabilizing | 0.982 | D | 0.555 | neutral | None | None | None | None | I |
| V/Q | 0.5525 | ambiguous | 0.5605 | ambiguous | -0.737 | Destabilizing | 0.996 | D | 0.543 | neutral | None | None | None | None | I |
| V/R | 0.6979 | likely_pathogenic | 0.6896 | pathogenic | -0.584 | Destabilizing | 0.999 | D | 0.588 | neutral | None | None | None | None | I |
| V/S | 0.3354 | likely_benign | 0.3375 | benign | -1.458 | Destabilizing | 0.993 | D | 0.527 | neutral | None | None | None | None | I |
| V/T | 0.2512 | likely_benign | 0.2472 | benign | -1.223 | Destabilizing | 0.942 | D | 0.436 | neutral | None | None | None | None | I |
| V/W | 0.9578 | likely_pathogenic | 0.9527 | pathogenic | -1.01 | Destabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | I |
| V/Y | 0.8359 | likely_pathogenic | 0.8138 | pathogenic | -0.639 | Destabilizing | 0.999 | D | 0.497 | 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.