Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14091 | 42496;42497;42498 | chr2:178634510;178634509;178634508 | chr2:179499237;179499236;179499235 |
| N2AB | 12450 | 37573;37574;37575 | chr2:178634510;178634509;178634508 | chr2:179499237;179499236;179499235 |
| N2A | 11523 | 34792;34793;34794 | chr2:178634510;178634509;178634508 | chr2:179499237;179499236;179499235 |
| N2B | 5026 | 15301;15302;15303 | chr2:178634510;178634509;178634508 | chr2:179499237;179499236;179499235 |
| Novex-1 | 5151 | 15676;15677;15678 | chr2:178634510;178634509;178634508 | chr2:179499237;179499236;179499235 |
| Novex-2 | 5218 | 15877;15878;15879 | chr2:178634510;178634509;178634508 | chr2:179499237;179499236;179499235 |
| 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/T | None | None | 0.98 | N | 0.485 | 0.351 | 0.723184643479 | gnomAD-4.0.0 | 1.5922E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85999E-06 | 0 | 0 |
| I/V | None | None | 0.4 | N | 0.208 | 0.093 | 0.51721326083 | gnomAD-4.0.0 | 1.20033E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.31251E-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 | 0.5611 | ambiguous | 0.5048 | ambiguous | -0.743 | Destabilizing | 0.964 | D | 0.487 | neutral | None | None | None | None | N |
| I/C | 0.8641 | likely_pathogenic | 0.833 | pathogenic | -0.65 | Destabilizing | 1.0 | D | 0.551 | neutral | None | None | None | None | N |
| I/D | 0.8234 | likely_pathogenic | 0.7764 | pathogenic | -0.065 | Destabilizing | 0.991 | D | 0.533 | neutral | None | None | None | None | N |
| I/E | 0.7187 | likely_pathogenic | 0.6712 | pathogenic | -0.143 | Destabilizing | 0.469 | N | 0.389 | neutral | None | None | None | None | N |
| I/F | 0.2907 | likely_benign | 0.2681 | benign | -0.681 | Destabilizing | 0.998 | D | 0.439 | neutral | None | None | None | None | N |
| I/G | 0.8536 | likely_pathogenic | 0.8128 | pathogenic | -0.932 | Destabilizing | 0.998 | D | 0.569 | neutral | None | None | None | None | N |
| I/H | 0.7032 | likely_pathogenic | 0.6611 | pathogenic | -0.231 | Destabilizing | 1.0 | D | 0.629 | neutral | None | None | None | None | N |
| I/K | 0.5664 | likely_pathogenic | 0.5262 | ambiguous | -0.371 | Destabilizing | 0.994 | D | 0.542 | neutral | N | 0.465334137 | None | None | N |
| I/L | 0.1879 | likely_benign | 0.1802 | benign | -0.36 | Destabilizing | 0.911 | D | 0.327 | neutral | N | 0.476116409 | None | None | N |
| I/M | 0.1547 | likely_benign | 0.1442 | benign | -0.394 | Destabilizing | 0.997 | D | 0.481 | neutral | N | 0.501156472 | None | None | N |
| I/N | 0.435 | ambiguous | 0.3738 | ambiguous | -0.151 | Destabilizing | 0.998 | D | 0.617 | neutral | None | None | None | None | N |
| I/P | 0.8178 | likely_pathogenic | 0.7962 | pathogenic | -0.454 | Destabilizing | 0.999 | D | 0.619 | neutral | None | None | None | None | N |
| I/Q | 0.6513 | likely_pathogenic | 0.5992 | pathogenic | -0.357 | Destabilizing | 0.996 | D | 0.619 | neutral | None | None | None | None | N |
| I/R | 0.4669 | ambiguous | 0.4296 | ambiguous | 0.156 | Stabilizing | 0.994 | D | 0.621 | neutral | N | 0.498748545 | None | None | N |
| I/S | 0.5273 | ambiguous | 0.472 | ambiguous | -0.66 | Destabilizing | 0.996 | D | 0.508 | neutral | None | None | None | None | N |
| I/T | 0.3641 | ambiguous | 0.3179 | benign | -0.623 | Destabilizing | 0.98 | D | 0.485 | neutral | N | 0.505415311 | None | None | N |
| I/V | 0.1014 | likely_benign | 0.0952 | benign | -0.454 | Destabilizing | 0.4 | N | 0.208 | neutral | N | 0.496745121 | None | None | N |
| I/W | 0.8815 | likely_pathogenic | 0.8645 | pathogenic | -0.692 | Destabilizing | 1.0 | D | 0.674 | neutral | None | None | None | None | N |
| I/Y | 0.6638 | likely_pathogenic | 0.6285 | pathogenic | -0.445 | Destabilizing | 0.999 | D | 0.498 | 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.