Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35423 | 106492;106493;106494 | chr2:178530348;178530347;178530346 | chr2:179395075;179395074;179395073 |
| N2AB | 33782 | 101569;101570;101571 | chr2:178530348;178530347;178530346 | chr2:179395075;179395074;179395073 |
| N2A | 32855 | 98788;98789;98790 | chr2:178530348;178530347;178530346 | chr2:179395075;179395074;179395073 |
| N2B | 26358 | 79297;79298;79299 | chr2:178530348;178530347;178530346 | chr2:179395075;179395074;179395073 |
| Novex-1 | 26483 | 79672;79673;79674 | chr2:178530348;178530347;178530346 | chr2:179395075;179395074;179395073 |
| Novex-2 | 26550 | 79873;79874;79875 | chr2:178530348;178530347;178530346 | chr2:179395075;179395074;179395073 |
| 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/F | rs763752622  |
-0.712 | 0.624 | N | 0.406 | 0.128 | 0.504968073517 | gnomAD-2.1.1 | 8.03E-06 | None | None | None | None | I | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.86E-06 | 0 |
| V/F | rs763752622 |
-0.712 | 0.624 | N | 0.406 | 0.128 | 0.504968073517 | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | I | None | 4.82E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 8.82E-05 | 0 | 0 |
| V/F | rs763752622 |
-0.712 | 0.624 | N | 0.406 | 0.128 | 0.504968073517 | gnomAD-4.0.0 | 1.92127E-05 | None | None | None | None | I | None | 5.07219E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.87096E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2137 | likely_benign | 0.1856 | benign | -0.572 | Destabilizing | 0.001 | N | 0.099 | neutral | N | 0.495670939 | None | None | I |
| V/C | 0.8391 | likely_pathogenic | 0.8051 | pathogenic | -0.78 | Destabilizing | 0.944 | D | 0.36 | neutral | None | None | None | None | I |
| V/D | 0.3579 | ambiguous | 0.3256 | benign | -0.433 | Destabilizing | 0.771 | D | 0.438 | neutral | N | 0.495497581 | None | None | I |
| V/E | 0.2607 | likely_benign | 0.2332 | benign | -0.54 | Destabilizing | 0.688 | D | 0.395 | neutral | None | None | None | None | I |
| V/F | 0.1717 | likely_benign | 0.1515 | benign | -0.71 | Destabilizing | 0.624 | D | 0.406 | neutral | N | 0.465695748 | None | None | I |
| V/G | 0.2844 | likely_benign | 0.262 | benign | -0.71 | Destabilizing | 0.192 | N | 0.368 | neutral | N | 0.466202727 | None | None | I |
| V/H | 0.613 | likely_pathogenic | 0.5484 | ambiguous | -0.18 | Destabilizing | 0.981 | D | 0.421 | neutral | None | None | None | None | I |
| V/I | 0.0825 | likely_benign | 0.0763 | benign | -0.357 | Destabilizing | 0.001 | N | 0.106 | neutral | N | 0.421671826 | None | None | I |
| V/K | 0.3651 | ambiguous | 0.3294 | benign | -0.597 | Destabilizing | 0.688 | D | 0.403 | neutral | None | None | None | None | I |
| V/L | 0.1976 | likely_benign | 0.1664 | benign | -0.357 | Destabilizing | 0.041 | N | 0.265 | neutral | N | 0.43290754 | None | None | I |
| V/M | 0.1732 | likely_benign | 0.1537 | benign | -0.452 | Destabilizing | 0.688 | D | 0.455 | neutral | None | None | None | None | I |
| V/N | 0.3204 | likely_benign | 0.2687 | benign | -0.408 | Destabilizing | 0.817 | D | 0.434 | neutral | None | None | None | None | I |
| V/P | 0.7319 | likely_pathogenic | 0.6958 | pathogenic | -0.394 | Destabilizing | 0.817 | D | 0.427 | neutral | None | None | None | None | I |
| V/Q | 0.3361 | likely_benign | 0.302 | benign | -0.652 | Destabilizing | 0.817 | D | 0.399 | neutral | None | None | None | None | I |
| V/R | 0.3185 | likely_benign | 0.2868 | benign | -0.028 | Destabilizing | 0.688 | D | 0.446 | neutral | None | None | None | None | I |
| V/S | 0.2418 | likely_benign | 0.2085 | benign | -0.767 | Destabilizing | 0.239 | N | 0.349 | neutral | None | None | None | None | I |
| V/T | 0.1893 | likely_benign | 0.1668 | benign | -0.774 | Destabilizing | 0.386 | N | 0.324 | neutral | None | None | None | None | I |
| V/W | 0.8422 | likely_pathogenic | 0.816 | pathogenic | -0.777 | Destabilizing | 0.981 | D | 0.565 | neutral | None | None | None | None | I |
| V/Y | 0.5846 | likely_pathogenic | 0.5314 | ambiguous | -0.498 | Destabilizing | 0.932 | D | 0.405 | 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.