Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32311 | 97156;97157;97158 | chr2:178542923;178542922;178542921 | chr2:179407650;179407649;179407648 |
| N2AB | 30670 | 92233;92234;92235 | chr2:178542923;178542922;178542921 | chr2:179407650;179407649;179407648 |
| N2A | 29743 | 89452;89453;89454 | chr2:178542923;178542922;178542921 | chr2:179407650;179407649;179407648 |
| N2B | 23246 | 69961;69962;69963 | chr2:178542923;178542922;178542921 | chr2:179407650;179407649;179407648 |
| Novex-1 | 23371 | 70336;70337;70338 | chr2:178542923;178542922;178542921 | chr2:179407650;179407649;179407648 |
| Novex-2 | 23438 | 70537;70538;70539 | chr2:178542923;178542922;178542921 | chr2:179407650;179407649;179407648 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/T | None | None | 0.425 | N | 0.392 | 0.219 | 0.579236789951 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| M/V | rs727504981  |
0.307 | 0.003 | N | 0.149 | 0.105 | 0.300449992093 | gnomAD-2.1.1 | 1.63E-05 | None | None | None | None | N | None | 0 | 2.93E-05 | None | 0 | 0 | None | 0 | None | 0 | 2.7E-05 | 0 |
| M/V | rs727504981 |
0.307 | 0.003 | N | 0.149 | 0.105 | 0.300449992093 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| M/V | rs727504981 |
0.307 | 0.003 | N | 0.149 | 0.105 | 0.300449992093 | gnomAD-4.0.0 | 1.55515E-05 | None | None | None | None | N | None | 0 | 1.67588E-05 | None | 0 | 0 | None | 0 | 1.64908E-04 | 1.95703E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.6061 | likely_pathogenic | 0.5662 | pathogenic | -1.338 | Destabilizing | 0.3 | N | 0.297 | neutral | None | None | None | None | N |
| M/C | 0.7803 | likely_pathogenic | 0.7389 | pathogenic | -1.082 | Destabilizing | 0.981 | D | 0.382 | neutral | None | None | None | None | N |
| M/D | 0.9278 | likely_pathogenic | 0.9095 | pathogenic | -0.024 | Destabilizing | 0.936 | D | 0.53 | neutral | None | None | None | None | N |
| M/E | 0.8211 | likely_pathogenic | 0.7841 | pathogenic | 0.013 | Stabilizing | 0.936 | D | 0.45 | neutral | None | None | None | None | N |
| M/F | 0.2848 | likely_benign | 0.2526 | benign | -0.393 | Destabilizing | 0.495 | N | 0.249 | neutral | None | None | None | None | N |
| M/G | 0.8427 | likely_pathogenic | 0.8155 | pathogenic | -1.653 | Destabilizing | 0.936 | D | 0.476 | neutral | None | None | None | None | N |
| M/H | 0.6539 | likely_pathogenic | 0.5925 | pathogenic | -0.723 | Destabilizing | 0.981 | D | 0.459 | neutral | None | None | None | None | N |
| M/I | 0.1886 | likely_benign | 0.1937 | benign | -0.536 | Destabilizing | 0.001 | N | 0.144 | neutral | N | 0.367106622 | None | None | N |
| M/K | 0.5303 | ambiguous | 0.4597 | ambiguous | -0.245 | Destabilizing | 0.784 | D | 0.429 | neutral | N | 0.395522588 | None | None | N |
| M/L | 0.098 | likely_benign | 0.0955 | benign | -0.536 | Destabilizing | 0.029 | N | 0.229 | neutral | N | 0.362026089 | None | None | N |
| M/N | 0.7252 | likely_pathogenic | 0.6993 | pathogenic | -0.178 | Destabilizing | 0.936 | D | 0.53 | neutral | None | None | None | None | N |
| M/P | 0.8976 | likely_pathogenic | 0.8641 | pathogenic | -0.775 | Destabilizing | 0.936 | D | 0.545 | neutral | None | None | None | None | N |
| M/Q | 0.5278 | ambiguous | 0.4773 | ambiguous | -0.197 | Destabilizing | 0.936 | D | 0.294 | neutral | None | None | None | None | N |
| M/R | 0.5383 | ambiguous | 0.446 | ambiguous | 0.15 | Stabilizing | 0.917 | D | 0.476 | neutral | N | 0.415244499 | None | None | N |
| M/S | 0.6497 | likely_pathogenic | 0.6052 | pathogenic | -0.8 | Destabilizing | 0.665 | D | 0.43 | neutral | None | None | None | None | N |
| M/T | 0.4834 | ambiguous | 0.442 | ambiguous | -0.637 | Destabilizing | 0.425 | N | 0.392 | neutral | N | 0.396389379 | None | None | N |
| M/V | 0.0822 | likely_benign | 0.0817 | benign | -0.775 | Destabilizing | 0.003 | N | 0.149 | neutral | N | 0.444700614 | None | None | N |
| M/W | 0.6553 | likely_pathogenic | 0.5816 | pathogenic | -0.355 | Destabilizing | 0.995 | D | 0.383 | neutral | None | None | None | None | N |
| M/Y | 0.5648 | likely_pathogenic | 0.5076 | ambiguous | -0.333 | Destabilizing | 0.936 | D | 0.459 | 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.