Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19809 | 59650;59651;59652 | chr2:178592580;178592579;178592578 | chr2:179457307;179457306;179457305 |
| N2AB | 18168 | 54727;54728;54729 | chr2:178592580;178592579;178592578 | chr2:179457307;179457306;179457305 |
| N2A | 17241 | 51946;51947;51948 | chr2:178592580;178592579;178592578 | chr2:179457307;179457306;179457305 |
| N2B | 10744 | 32455;32456;32457 | chr2:178592580;178592579;178592578 | chr2:179457307;179457306;179457305 |
| Novex-1 | 10869 | 32830;32831;32832 | chr2:178592580;178592579;178592578 | chr2:179457307;179457306;179457305 |
| Novex-2 | 10936 | 33031;33032;33033 | chr2:178592580;178592579;178592578 | chr2:179457307;179457306;179457305 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/V | rs754507241  |
-0.05 | None | N | 0.135 | 0.11 | 0.223146558224 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| I/V | rs754507241 |
-0.05 | None | N | 0.135 | 0.11 | 0.223146558224 | gnomAD-4.0.0 | 1.59192E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85945E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.4113 | ambiguous | 0.2522 | benign | -0.545 | Destabilizing | 0.007 | N | 0.277 | neutral | None | None | None | None | I |
| I/C | 0.7178 | likely_pathogenic | 0.6113 | pathogenic | -0.831 | Destabilizing | 0.356 | N | 0.505 | neutral | None | None | None | None | I |
| I/D | 0.7906 | likely_pathogenic | 0.6494 | pathogenic | -0.138 | Destabilizing | 0.136 | N | 0.528 | neutral | None | None | None | None | I |
| I/E | 0.6959 | likely_pathogenic | 0.5514 | ambiguous | -0.219 | Destabilizing | 0.136 | N | 0.538 | neutral | None | None | None | None | I |
| I/F | 0.2442 | likely_benign | 0.1726 | benign | -0.548 | Destabilizing | 0.055 | N | 0.425 | neutral | N | 0.48390016 | None | None | I |
| I/G | 0.6833 | likely_pathogenic | 0.491 | ambiguous | -0.683 | Destabilizing | None | N | 0.303 | neutral | None | None | None | None | I |
| I/H | 0.611 | likely_pathogenic | 0.4712 | ambiguous | 0.053 | Stabilizing | 0.628 | D | 0.499 | neutral | None | None | None | None | I |
| I/K | 0.5431 | ambiguous | 0.3861 | ambiguous | -0.392 | Destabilizing | 0.136 | N | 0.535 | neutral | None | None | None | None | I |
| I/L | 0.1395 | likely_benign | 0.1137 | benign | -0.3 | Destabilizing | 0.005 | N | 0.197 | neutral | N | 0.476915473 | None | None | I |
| I/M | 0.1244 | likely_benign | 0.0937 | benign | -0.561 | Destabilizing | 0.171 | N | 0.436 | neutral | N | 0.508507816 | None | None | I |
| I/N | 0.3462 | ambiguous | 0.2288 | benign | -0.303 | Destabilizing | 0.106 | N | 0.555 | neutral | N | 0.472104299 | None | None | I |
| I/P | 0.9158 | likely_pathogenic | 0.8894 | pathogenic | -0.351 | Destabilizing | 0.136 | N | 0.559 | neutral | None | None | None | None | I |
| I/Q | 0.5484 | ambiguous | 0.3933 | ambiguous | -0.471 | Destabilizing | 0.628 | D | 0.529 | neutral | None | None | None | None | I |
| I/R | 0.4723 | ambiguous | 0.3411 | ambiguous | 0.105 | Stabilizing | 0.356 | N | 0.547 | neutral | None | None | None | None | I |
| I/S | 0.3782 | ambiguous | 0.2431 | benign | -0.732 | Destabilizing | 0.012 | N | 0.455 | neutral | N | 0.451459668 | None | None | I |
| I/T | 0.2816 | likely_benign | 0.1588 | benign | -0.705 | Destabilizing | None | N | 0.184 | neutral | N | 0.412015845 | None | None | I |
| I/V | 0.0685 | likely_benign | 0.0567 | benign | -0.351 | Destabilizing | None | N | 0.135 | neutral | N | 0.443514975 | None | None | I |
| I/W | 0.8276 | likely_pathogenic | 0.7877 | pathogenic | -0.566 | Destabilizing | 0.864 | D | 0.504 | neutral | None | None | None | None | I |
| I/Y | 0.5474 | ambiguous | 0.49 | ambiguous | -0.336 | Destabilizing | 0.356 | N | 0.533 | 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.