Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35908 | 107947;107948;107949 | chr2:178527266;178527265;178527264 | chr2:179391993;179391992;179391991 |
| N2AB | 34267 | 103024;103025;103026 | chr2:178527266;178527265;178527264 | chr2:179391993;179391992;179391991 |
| N2A | 33340 | 100243;100244;100245 | chr2:178527266;178527265;178527264 | chr2:179391993;179391992;179391991 |
| N2B | 26843 | 80752;80753;80754 | chr2:178527266;178527265;178527264 | chr2:179391993;179391992;179391991 |
| Novex-1 | 26968 | 81127;81128;81129 | chr2:178527266;178527265;178527264 | chr2:179391993;179391992;179391991 |
| Novex-2 | 27035 | 81328;81329;81330 | chr2:178527266;178527265;178527264 | chr2:179391993;179391992;179391991 |
| 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/L | None | None | 0.993 | N | 0.305 | 0.326 | 0.48286525802 | gnomAD-4.0.0 | 8.92808E-06 | None | None | None | -1.01(OBSL1) -1.08(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.1734E-05 | 0 | 0 |
| I/M | None | None | 1.0 | N | 0.585 | 0.492 | 0.406806705197 | gnomAD-4.0.0 | 2.05723E-06 | None | None | None | -1.264(OBSL1) -1.082(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.7043E-06 | 0 | 0 |
| I/T | rs769141222  |
-3.038 | 1.0 | N | 0.55 | 0.507 | None | gnomAD-2.1.1 | 2.87E-05 | None | None | None | -0.937(OBSL1) -0.198(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.29E-05 | 0 |
| I/T | rs769141222 |
-3.038 | 1.0 | N | 0.55 | 0.507 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | -0.937(OBSL1) -0.198(OBSCN) | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| I/T | rs769141222 |
-3.038 | 1.0 | N | 0.55 | 0.507 | None | gnomAD-4.0.0 | 6.20981E-05 | None | None | None | -0.937(OBSL1) -0.198(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.49408E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.5743 | likely_pathogenic | 0.7453 | pathogenic | -2.295 | Highly Destabilizing | 0.999 | D | 0.471 | neutral | None | None | None | -0.736(OBSL1) -0.662(OBSCN) | N |
| I/C | 0.9356 | likely_pathogenic | 0.9645 | pathogenic | -1.655 | Destabilizing | 1.0 | D | 0.554 | neutral | None | None | None | -1.411(OBSL1) -0.537(OBSCN) | N |
| I/D | 0.9869 | likely_pathogenic | 0.9927 | pathogenic | -2.042 | Highly Destabilizing | 1.0 | D | 0.629 | neutral | None | None | None | -1.852(OBSL1) -0.461(OBSCN) | N |
| I/E | 0.9533 | likely_pathogenic | 0.9738 | pathogenic | -1.926 | Destabilizing | 1.0 | D | 0.624 | neutral | None | None | None | -1.982(OBSL1) -0.565(OBSCN) | N |
| I/F | 0.5572 | ambiguous | 0.6657 | pathogenic | -1.48 | Destabilizing | 1.0 | D | 0.569 | neutral | N | 0.510396115 | None | -0.514(OBSL1) -1.53(OBSCN) | N |
| I/G | 0.9544 | likely_pathogenic | 0.9789 | pathogenic | -2.746 | Highly Destabilizing | 1.0 | D | 0.621 | neutral | None | None | None | -0.674(OBSL1) -0.533(OBSCN) | N |
| I/H | 0.9718 | likely_pathogenic | 0.9867 | pathogenic | -2.015 | Highly Destabilizing | 1.0 | D | 0.662 | neutral | None | None | None | -0.675(OBSL1) -0.377(OBSCN) | N |
| I/K | 0.9253 | likely_pathogenic | 0.9606 | pathogenic | -1.662 | Destabilizing | 1.0 | D | 0.628 | neutral | None | None | None | -1.751(OBSL1) -0.441(OBSCN) | N |
| I/L | 0.2977 | likely_benign | 0.3791 | ambiguous | -1.051 | Destabilizing | 0.993 | D | 0.305 | neutral | N | 0.4879219 | None | -1.01(OBSL1) -1.08(OBSCN) | N |
| I/M | 0.2032 | likely_benign | 0.2623 | benign | -0.961 | Destabilizing | 1.0 | D | 0.585 | neutral | N | 0.50397853 | None | -1.264(OBSL1) -1.082(OBSCN) | N |
| I/N | 0.9168 | likely_pathogenic | 0.9514 | pathogenic | -1.696 | Destabilizing | 1.0 | D | 0.65 | neutral | N | 0.504738999 | None | -0.926(OBSL1) -0.413(OBSCN) | N |
| I/P | 0.9771 | likely_pathogenic | 0.9849 | pathogenic | -1.44 | Destabilizing | 1.0 | D | 0.648 | neutral | None | None | None | -0.904(OBSL1) -0.938(OBSCN) | N |
| I/Q | 0.9401 | likely_pathogenic | 0.9692 | pathogenic | -1.74 | Destabilizing | 1.0 | D | 0.639 | neutral | None | None | None | -1.148(OBSL1) -0.521(OBSCN) | N |
| I/R | 0.8833 | likely_pathogenic | 0.9335 | pathogenic | -1.187 | Destabilizing | 1.0 | D | 0.655 | neutral | None | None | None | -1.707(OBSL1) -0.405(OBSCN) | N |
| I/S | 0.777 | likely_pathogenic | 0.8728 | pathogenic | -2.425 | Highly Destabilizing | 1.0 | D | 0.547 | neutral | N | 0.516052651 | None | -0.793(OBSL1) -0.044(OBSCN) | N |
| I/T | 0.3905 | ambiguous | 0.5679 | pathogenic | -2.176 | Highly Destabilizing | 1.0 | D | 0.55 | neutral | N | 0.503238069 | None | -0.937(OBSL1) -0.198(OBSCN) | N |
| I/V | 0.0941 | likely_benign | 0.1222 | benign | -1.44 | Destabilizing | 0.993 | D | 0.318 | neutral | N | 0.413053208 | None | -0.904(OBSL1) -0.938(OBSCN) | N |
| I/W | 0.9757 | likely_pathogenic | 0.9837 | pathogenic | -1.687 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | -0.897(OBSL1) -1.928(OBSCN) | N |
| I/Y | 0.9412 | likely_pathogenic | 0.9632 | pathogenic | -1.438 | Destabilizing | 1.0 | D | 0.543 | neutral | None | None | None | -0.494(OBSL1) -1.566(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.