Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22420 | 67483;67484;67485 | chr2:178580029;178580028;178580027 | chr2:179444756;179444755;179444754 |
| N2AB | 20779 | 62560;62561;62562 | chr2:178580029;178580028;178580027 | chr2:179444756;179444755;179444754 |
| N2A | 19852 | 59779;59780;59781 | chr2:178580029;178580028;178580027 | chr2:179444756;179444755;179444754 |
| N2B | 13355 | 40288;40289;40290 | chr2:178580029;178580028;178580027 | chr2:179444756;179444755;179444754 |
| Novex-1 | 13480 | 40663;40664;40665 | chr2:178580029;178580028;178580027 | chr2:179444756;179444755;179444754 |
| Novex-2 | 13547 | 40864;40865;40866 | chr2:178580029;178580028;178580027 | chr2:179444756;179444755;179444754 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/G | rs1356121178  |
-0.747 | 0.704 | N | 0.394 | 0.324 | 0.354822389136 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| E/G | rs1356121178 |
-0.747 | 0.704 | N | 0.394 | 0.324 | 0.354822389136 | gnomAD-4.0.0 | 1.20034E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.66327E-05 |
| E/K | rs530426755 |
0.514 | 0.92 | N | 0.434 | 0.293 | 0.264081493735 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.94099E-04 | None | 0 | 0 | 0 | 0 | 0 |
| E/K | rs530426755 |
0.514 | 0.92 | N | 0.434 | 0.293 | 0.264081493735 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| E/K | rs530426755 |
0.514 | 0.92 | N | 0.434 | 0.293 | 0.264081493735 | gnomAD-4.0.0 | 6.57099E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.94553E-04 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.1741 | likely_benign | 0.1683 | benign | -0.358 | Destabilizing | 0.061 | N | 0.165 | neutral | N | 0.515593212 | None | None | N |
| E/C | 0.9404 | likely_pathogenic | 0.928 | pathogenic | 0.054 | Stabilizing | 0.999 | D | 0.466 | neutral | None | None | None | None | N |
| E/D | 0.4344 | ambiguous | 0.3517 | ambiguous | -0.352 | Destabilizing | 0.826 | D | 0.457 | neutral | N | 0.509516305 | None | None | N |
| E/F | 0.9473 | likely_pathogenic | 0.9408 | pathogenic | -0.334 | Destabilizing | 0.997 | D | 0.489 | neutral | None | None | None | None | N |
| E/G | 0.3913 | ambiguous | 0.3433 | ambiguous | -0.555 | Destabilizing | 0.704 | D | 0.394 | neutral | N | 0.501376004 | None | None | N |
| E/H | 0.8649 | likely_pathogenic | 0.8218 | pathogenic | -0.188 | Destabilizing | 0.997 | D | 0.381 | neutral | None | None | None | None | N |
| E/I | 0.5553 | ambiguous | 0.5312 | ambiguous | 0.123 | Stabilizing | 0.991 | D | 0.511 | neutral | None | None | None | None | N |
| E/K | 0.3691 | ambiguous | 0.3272 | benign | 0.287 | Stabilizing | 0.92 | D | 0.434 | neutral | N | 0.482498054 | None | None | N |
| E/L | 0.7288 | likely_pathogenic | 0.6949 | pathogenic | 0.123 | Stabilizing | 0.939 | D | 0.491 | neutral | None | None | None | None | N |
| E/M | 0.6911 | likely_pathogenic | 0.6658 | pathogenic | 0.288 | Stabilizing | 0.999 | D | 0.449 | neutral | None | None | None | None | N |
| E/N | 0.6292 | likely_pathogenic | 0.5568 | ambiguous | 0.076 | Stabilizing | 0.939 | D | 0.436 | neutral | None | None | None | None | N |
| E/P | 0.4353 | ambiguous | 0.4192 | ambiguous | -0.017 | Destabilizing | 0.991 | D | 0.442 | neutral | None | None | None | None | N |
| E/Q | 0.286 | likely_benign | 0.2702 | benign | 0.092 | Stabilizing | 0.959 | D | 0.498 | neutral | N | 0.479295276 | None | None | N |
| E/R | 0.5549 | ambiguous | 0.5131 | ambiguous | 0.45 | Stabilizing | 0.991 | D | 0.403 | neutral | None | None | None | None | N |
| E/S | 0.4164 | ambiguous | 0.3685 | ambiguous | -0.113 | Destabilizing | 0.373 | N | 0.157 | neutral | None | None | None | None | N |
| E/T | 0.4378 | ambiguous | 0.3802 | ambiguous | 0.042 | Stabilizing | 0.884 | D | 0.386 | neutral | None | None | None | None | N |
| E/V | 0.3438 | ambiguous | 0.3321 | benign | -0.017 | Destabilizing | 0.92 | D | 0.452 | neutral | N | 0.497995416 | None | None | N |
| E/W | 0.9875 | likely_pathogenic | 0.9825 | pathogenic | -0.217 | Destabilizing | 0.999 | D | 0.569 | neutral | None | None | None | None | N |
| E/Y | 0.9124 | likely_pathogenic | 0.8932 | pathogenic | -0.097 | Destabilizing | 0.997 | D | 0.46 | 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.