Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3987 | 12184;12185;12186 | chr2:178741274;178741273;178741272 | chr2:179606001;179606000;179605999 |
| N2AB | 3670 | 11233;11234;11235 | chr2:178741274;178741273;178741272 | chr2:179606001;179606000;179605999 |
| N2A | None | None | chr2:None | chr2:None |
| N2B | 3624 | 11095;11096;11097 | chr2:178741274;178741273;178741272 | chr2:179606001;179606000;179605999 |
| Novex-1 | 3749 | 11470;11471;11472 | chr2:178741274;178741273;178741272 | chr2:179606001;179606000;179605999 |
| Novex-2 | 3816 | 11671;11672;11673 | chr2:178741274;178741273;178741272 | chr2:179606001;179606000;179605999 |
| 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 | rs551387805  |
-0.308 | 0.01 | N | 0.114 | 0.091 | None | gnomAD-2.1.1 | 2.13292E-04 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 1.60131E-03 | None | 0 | 3.56E-05 | 0 |
| I/V | rs551387805 |
-0.308 | 0.01 | N | 0.114 | 0.091 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 1.03434E-03 | 0 |
| I/V | rs551387805 |
-0.308 | 0.01 | N | 0.114 | 0.091 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| I/V | rs551387805 |
-0.308 | 0.01 | N | 0.114 | 0.091 | None | gnomAD-4.0.0 | 1.1215E-04 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69514E-05 | 1.71263E-03 | 8.00256E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.6986 | likely_pathogenic | 0.6323 | pathogenic | -0.993 | Destabilizing | 0.003 | N | 0.162 | neutral | None | None | None | None | I |
| I/C | 0.8286 | likely_pathogenic | 0.7856 | pathogenic | -0.716 | Destabilizing | 0.944 | D | 0.36 | neutral | None | None | None | None | I |
| I/D | 0.8904 | likely_pathogenic | 0.86 | pathogenic | -0.442 | Destabilizing | 0.704 | D | 0.444 | neutral | None | None | None | None | I |
| I/E | 0.7988 | likely_pathogenic | 0.7521 | pathogenic | -0.509 | Destabilizing | 0.704 | D | 0.406 | neutral | None | None | None | None | I |
| I/F | 0.2303 | likely_benign | 0.2023 | benign | -0.796 | Destabilizing | 0.863 | D | 0.319 | neutral | N | 0.507392126 | None | None | I |
| I/G | 0.8946 | likely_pathogenic | 0.8571 | pathogenic | -1.214 | Destabilizing | 0.329 | N | 0.393 | neutral | None | None | None | None | I |
| I/H | 0.6487 | likely_pathogenic | 0.6088 | pathogenic | -0.4 | Destabilizing | 0.995 | D | 0.361 | neutral | None | None | None | None | I |
| I/K | 0.6305 | likely_pathogenic | 0.5818 | pathogenic | -0.646 | Destabilizing | 0.704 | D | 0.405 | neutral | None | None | None | None | I |
| I/L | 0.1768 | likely_benign | 0.1586 | benign | -0.51 | Destabilizing | 0.002 | N | 0.091 | neutral | N | 0.503291722 | None | None | I |
| I/M | 0.1858 | likely_benign | 0.1742 | benign | -0.435 | Destabilizing | 0.863 | D | 0.345 | neutral | N | 0.501245354 | None | None | I |
| I/N | 0.4761 | ambiguous | 0.44 | ambiguous | -0.435 | Destabilizing | 0.642 | D | 0.425 | neutral | D | 0.58517744 | None | None | I |
| I/P | 0.9592 | likely_pathogenic | 0.9445 | pathogenic | -0.637 | Destabilizing | 0.944 | D | 0.442 | neutral | None | None | None | None | I |
| I/Q | 0.6499 | likely_pathogenic | 0.6069 | pathogenic | -0.666 | Destabilizing | 0.944 | D | 0.424 | neutral | None | None | None | None | I |
| I/R | 0.4914 | ambiguous | 0.4435 | ambiguous | -0.018 | Destabilizing | 0.893 | D | 0.438 | neutral | None | None | None | None | I |
| I/S | 0.5084 | ambiguous | 0.4633 | ambiguous | -0.951 | Destabilizing | 0.01 | N | 0.205 | neutral | N | 0.489773924 | None | None | I |
| I/T | 0.4554 | ambiguous | 0.4015 | ambiguous | -0.908 | Destabilizing | 0.023 | N | 0.191 | neutral | N | 0.501282241 | None | None | I |
| I/V | 0.1701 | likely_benign | 0.1545 | benign | -0.637 | Destabilizing | 0.01 | N | 0.114 | neutral | N | 0.480680471 | None | None | I |
| I/W | 0.8603 | likely_pathogenic | 0.8287 | pathogenic | -0.805 | Destabilizing | 0.995 | D | 0.389 | neutral | None | None | None | None | I |
| I/Y | 0.6425 | likely_pathogenic | 0.6052 | pathogenic | -0.581 | Destabilizing | 0.981 | D | 0.393 | 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.