Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35932 | 108019;108020;108021 | chr2:178527194;178527193;178527192 | chr2:179391921;179391920;179391919 |
| N2AB | 34291 | 103096;103097;103098 | chr2:178527194;178527193;178527192 | chr2:179391921;179391920;179391919 |
| N2A | 33364 | 100315;100316;100317 | chr2:178527194;178527193;178527192 | chr2:179391921;179391920;179391919 |
| N2B | 26867 | 80824;80825;80826 | chr2:178527194;178527193;178527192 | chr2:179391921;179391920;179391919 |
| Novex-1 | 26992 | 81199;81200;81201 | chr2:178527194;178527193;178527192 | chr2:179391921;179391920;179391919 |
| Novex-2 | 27059 | 81400;81401;81402 | chr2:178527194;178527193;178527192 | chr2:179391921;179391920;179391919 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/S | rs557626982  |
0.067 | 0.006 | N | 0.359 | 0.119 | 0.27132560031 | gnomAD-2.1.1 | 4.01E-06 | None | None | None | -0.916(OBSL1) -1.201(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| C/S | rs557626982 |
0.067 | 0.006 | N | 0.359 | 0.119 | 0.27132560031 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | -0.916(OBSL1) -1.201(OBSCN) | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.06954E-04 | 0 |
| C/S | rs557626982 |
0.067 | 0.006 | N | 0.359 | 0.119 | 0.27132560031 | 1000 genomes | 1.99681E-04 | None | None | None | -0.916(OBSL1) -1.201(OBSCN) | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| C/S | rs557626982 |
0.067 | 0.006 | N | 0.359 | 0.119 | 0.27132560031 | gnomAD-4.0.0 | 1.36831E-06 | None | None | None | -0.916(OBSL1) -1.201(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79881E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/A | 0.2843 | likely_benign | 0.2993 | benign | -1.419 | Destabilizing | 0.004 | N | 0.335 | neutral | None | None | None | -0.785(OBSL1) -1.079(OBSCN) | N |
| C/D | 0.5315 | ambiguous | 0.549 | ambiguous | 0.644 | Stabilizing | 0.018 | N | 0.473 | neutral | None | None | None | -0.651(OBSL1) -0.911(OBSCN) | N |
| C/E | 0.5195 | ambiguous | 0.5365 | ambiguous | 0.695 | Stabilizing | 0.004 | N | 0.391 | neutral | None | None | None | -0.727(OBSL1) -0.944(OBSCN) | N |
| C/F | 0.1406 | likely_benign | 0.1404 | benign | -1.191 | Destabilizing | 0.017 | N | 0.555 | neutral | N | 0.403931427 | None | -1.09(OBSL1) -0.835(OBSCN) | N |
| C/G | 0.1755 | likely_benign | 0.186 | benign | -1.649 | Destabilizing | 0.014 | N | 0.398 | neutral | N | 0.448338352 | None | -0.769(OBSL1) -1.115(OBSCN) | N |
| C/H | 0.1387 | likely_benign | 0.1354 | benign | -1.774 | Destabilizing | None | N | 0.327 | neutral | None | None | None | -0.116(OBSL1) -0.319(OBSCN) | N |
| C/I | 0.3793 | ambiguous | 0.3926 | ambiguous | -0.86 | Destabilizing | 0.044 | N | 0.528 | neutral | None | None | None | -0.857(OBSL1) -0.986(OBSCN) | N |
| C/K | 0.2801 | likely_benign | 0.2772 | benign | -0.091 | Destabilizing | None | N | 0.325 | neutral | None | None | None | -0.698(OBSL1) -0.953(OBSCN) | N |
| C/L | 0.2821 | likely_benign | 0.2864 | benign | -0.86 | Destabilizing | 0.004 | N | 0.362 | neutral | None | None | None | -0.857(OBSL1) -0.986(OBSCN) | N |
| C/M | 0.5251 | ambiguous | 0.5336 | ambiguous | -0.445 | Destabilizing | 0.497 | N | 0.513 | neutral | None | None | None | -0.708(OBSL1) -0.616(OBSCN) | N |
| C/N | 0.3373 | likely_benign | 0.3482 | ambiguous | 0.053 | Stabilizing | 0.009 | N | 0.428 | neutral | None | None | None | -1.084(OBSL1) -1.269(OBSCN) | N |
| C/P | 0.8668 | likely_pathogenic | 0.8875 | pathogenic | -1.022 | Destabilizing | 0.085 | N | 0.596 | neutral | None | None | None | -0.829(OBSL1) -1.013(OBSCN) | N |
| C/Q | 0.1791 | likely_benign | 0.1834 | benign | 0.078 | Stabilizing | 0.009 | N | 0.476 | neutral | None | None | None | -0.981(OBSL1) -1.108(OBSCN) | N |
| C/R | 0.0712 | likely_benign | 0.0703 | benign | -0.108 | Destabilizing | None | N | 0.306 | neutral | N | 0.322582267 | None | -0.536(OBSL1) -0.787(OBSCN) | N |
| C/S | 0.2085 | likely_benign | 0.2219 | benign | -0.52 | Destabilizing | 0.006 | N | 0.359 | neutral | N | 0.413687061 | None | -0.916(OBSL1) -1.201(OBSCN) | N |
| C/T | 0.3598 | ambiguous | 0.3705 | ambiguous | -0.287 | Destabilizing | 0.018 | N | 0.39 | neutral | None | None | None | -0.995(OBSL1) -1.173(OBSCN) | N |
| C/V | 0.3276 | likely_benign | 0.3407 | ambiguous | -1.022 | Destabilizing | 0.018 | N | 0.402 | neutral | None | None | None | -0.829(OBSL1) -1.013(OBSCN) | N |
| C/W | 0.2493 | likely_benign | 0.2624 | benign | -1.091 | Destabilizing | 0.196 | N | 0.593 | neutral | N | 0.472850008 | None | -1.284(OBSL1) -0.822(OBSCN) | N |
| C/Y | 0.1363 | likely_benign | 0.1386 | benign | -1.016 | Destabilizing | None | N | 0.269 | neutral | N | 0.424114698 | None | -1.117(OBSL1) -0.775(OBSCN) | 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.