Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30039 | 90340;90341;90342 | chr2:178552785;178552784;178552783 | chr2:179417512;179417511;179417510 |
| N2AB | 28398 | 85417;85418;85419 | chr2:178552785;178552784;178552783 | chr2:179417512;179417511;179417510 |
| N2A | 27471 | 82636;82637;82638 | chr2:178552785;178552784;178552783 | chr2:179417512;179417511;179417510 |
| N2B | 20974 | 63145;63146;63147 | chr2:178552785;178552784;178552783 | chr2:179417512;179417511;179417510 |
| Novex-1 | 21099 | 63520;63521;63522 | chr2:178552785;178552784;178552783 | chr2:179417512;179417511;179417510 |
| Novex-2 | 21166 | 63721;63722;63723 | chr2:178552785;178552784;178552783 | chr2:179417512;179417511;179417510 |
| 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/V | rs778266858  |
0.11 | None | N | 0.165 | 0.044 | 0.0551355673512 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 1.77E-05 | 0 |
| M/V | rs778266858 |
0.11 | None | N | 0.165 | 0.044 | 0.0551355673512 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.78927E-04 |
| M/V | rs778266858 |
0.11 | None | N | 0.165 | 0.044 | 0.0551355673512 | gnomAD-4.0.0 | 4.95718E-06 | None | None | None | None | N | None | 1.33426E-05 | 3.33356E-05 | None | 0 | 0 | None | 0 | 0 | 1.69515E-06 | 1.09777E-05 | 3.20205E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.4837 | ambiguous | 0.4118 | ambiguous | -1.266 | Destabilizing | 0.035 | N | 0.422 | neutral | None | None | None | None | N |
| M/C | 0.6482 | likely_pathogenic | 0.6189 | pathogenic | -1.168 | Destabilizing | 0.824 | D | 0.585 | neutral | None | None | None | None | N |
| M/D | 0.9511 | likely_pathogenic | 0.9244 | pathogenic | 0.315 | Stabilizing | 0.555 | D | 0.656 | neutral | None | None | None | None | N |
| M/E | 0.7165 | likely_pathogenic | 0.6177 | pathogenic | 0.378 | Stabilizing | 0.555 | D | 0.639 | neutral | None | None | None | None | N |
| M/F | 0.4111 | ambiguous | 0.376 | ambiguous | -0.203 | Destabilizing | 0.149 | N | 0.535 | neutral | None | None | None | None | N |
| M/G | 0.7622 | likely_pathogenic | 0.6645 | pathogenic | -1.604 | Destabilizing | 0.262 | N | 0.669 | neutral | None | None | None | None | N |
| M/H | 0.751 | likely_pathogenic | 0.7149 | pathogenic | -0.575 | Destabilizing | 0.935 | D | 0.605 | neutral | None | None | None | None | N |
| M/I | 0.2935 | likely_benign | 0.2366 | benign | -0.393 | Destabilizing | 0.009 | N | 0.43 | neutral | N | 0.356015342 | None | None | N |
| M/K | 0.3985 | ambiguous | 0.3441 | ambiguous | -0.123 | Destabilizing | 0.211 | N | 0.59 | neutral | N | 0.441482243 | None | None | N |
| M/L | 0.1231 | likely_benign | 0.1214 | benign | -0.393 | Destabilizing | None | N | 0.117 | neutral | N | 0.382585868 | None | None | N |
| M/N | 0.7743 | likely_pathogenic | 0.7162 | pathogenic | -0.131 | Destabilizing | 0.791 | D | 0.641 | neutral | None | None | None | None | N |
| M/P | 0.6813 | likely_pathogenic | 0.6227 | pathogenic | -0.655 | Destabilizing | 0.791 | D | 0.643 | neutral | None | None | None | None | N |
| M/Q | 0.3949 | ambiguous | 0.3439 | ambiguous | -0.086 | Destabilizing | 0.791 | D | 0.541 | neutral | None | None | None | None | N |
| M/R | 0.3961 | ambiguous | 0.3443 | ambiguous | 0.199 | Stabilizing | 0.484 | N | 0.62 | neutral | N | 0.49383386 | None | None | N |
| M/S | 0.6338 | likely_pathogenic | 0.5588 | ambiguous | -0.834 | Destabilizing | 0.149 | N | 0.535 | neutral | None | None | None | None | N |
| M/T | 0.3969 | ambiguous | 0.336 | benign | -0.636 | Destabilizing | 0.062 | N | 0.515 | neutral | N | 0.445445268 | None | None | N |
| M/V | 0.0695 | likely_benign | 0.0571 | benign | -0.655 | Destabilizing | None | N | 0.165 | neutral | N | 0.293635945 | None | None | N |
| M/W | 0.7128 | likely_pathogenic | 0.6816 | pathogenic | -0.173 | Destabilizing | 0.935 | D | 0.566 | neutral | None | None | None | None | N |
| M/Y | 0.673 | likely_pathogenic | 0.642 | pathogenic | -0.143 | Destabilizing | 0.555 | D | 0.611 | 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.