Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 6991 | 21196;21197;21198 | chr2:178724404;178724403;178724402 | chr2:179589131;179589130;179589129 |
| N2AB | 6674 | 20245;20246;20247 | chr2:178724404;178724403;178724402 | chr2:179589131;179589130;179589129 |
| N2A | 5747 | 17464;17465;17466 | chr2:178724404;178724403;178724402 | chr2:179589131;179589130;179589129 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/I | rs373585016  |
0.119 | 0.966 | N | 0.388 | 0.375 | 0.500426043041 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| S/I | rs373585016 |
0.119 | 0.966 | N | 0.388 | 0.375 | 0.500426043041 | gnomAD-4.0.0 | 2.7373E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.04032E-05 | None | 0 | 0 | 8.99599E-07 | 1.15947E-05 | 0 |
| S/N | rs373585016 |
0.126 | 0.012 | N | 0.309 | 0.155 | None | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| S/N | rs373585016 |
0.126 | 0.012 | N | 0.309 | 0.155 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| S/N | rs373585016 |
0.126 | 0.012 | N | 0.309 | 0.155 | None | gnomAD-4.0.0 | 1.05364E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.27161E-05 | 0 | 3.20307E-05 |
| S/R | rs778559152 |
0.1 | 0.934 | N | 0.311 | 0.235 | 0.241078983079 | gnomAD-2.1.1 | 2.14E-05 | None | None | None | None | I | None | 0 | 2.83E-05 | None | 0 | 0 | None | 0 | None | 0 | 3.13E-05 | 1.40687E-04 |
| S/R | rs778559152 |
0.1 | 0.934 | N | 0.311 | 0.235 | 0.241078983079 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| S/R | rs778559152 |
0.1 | 0.934 | N | 0.311 | 0.235 | 0.241078983079 | gnomAD-4.0.0 | 1.02529E-05 | None | None | None | None | I | None | 0 | 3.39179E-05 | None | 0 | 0 | None | 0 | 0 | 1.43647E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1807 | likely_benign | 0.157 | benign | -0.401 | Destabilizing | 0.525 | D | 0.391 | neutral | None | None | None | None | I |
| S/C | 0.1975 | likely_benign | 0.1881 | benign | -0.278 | Destabilizing | 0.997 | D | 0.332 | neutral | N | 0.495920458 | None | None | I |
| S/D | 0.2864 | likely_benign | 0.2469 | benign | 0.2 | Stabilizing | 0.728 | D | 0.3 | neutral | None | None | None | None | I |
| S/E | 0.6552 | likely_pathogenic | 0.6153 | pathogenic | 0.124 | Stabilizing | 0.842 | D | 0.286 | neutral | None | None | None | None | I |
| S/F | 0.4555 | ambiguous | 0.3895 | ambiguous | -0.891 | Destabilizing | 0.991 | D | 0.375 | neutral | None | None | None | None | I |
| S/G | 0.0926 | likely_benign | 0.0796 | benign | -0.547 | Destabilizing | 0.002 | N | 0.187 | neutral | N | 0.484741869 | None | None | I |
| S/H | 0.4687 | ambiguous | 0.4285 | ambiguous | -1.019 | Destabilizing | 0.974 | D | 0.285 | neutral | None | None | None | None | I |
| S/I | 0.3803 | ambiguous | 0.3211 | benign | -0.144 | Destabilizing | 0.966 | D | 0.388 | neutral | N | 0.481677316 | None | None | I |
| S/K | 0.8141 | likely_pathogenic | 0.7657 | pathogenic | -0.531 | Destabilizing | 0.842 | D | 0.284 | neutral | None | None | None | None | I |
| S/L | 0.2271 | likely_benign | 0.192 | benign | -0.144 | Destabilizing | 0.915 | D | 0.345 | neutral | None | None | None | None | I |
| S/M | 0.4204 | ambiguous | 0.3551 | ambiguous | 0.045 | Stabilizing | 0.998 | D | 0.289 | neutral | None | None | None | None | I |
| S/N | 0.1341 | likely_benign | 0.1084 | benign | -0.267 | Destabilizing | 0.012 | N | 0.309 | neutral | N | 0.501559548 | None | None | I |
| S/P | 0.6266 | likely_pathogenic | 0.618 | pathogenic | -0.199 | Destabilizing | 0.991 | D | 0.305 | neutral | None | None | None | None | I |
| S/Q | 0.6768 | likely_pathogenic | 0.6329 | pathogenic | -0.475 | Destabilizing | 0.974 | D | 0.331 | neutral | None | None | None | None | I |
| S/R | 0.7189 | likely_pathogenic | 0.6804 | pathogenic | -0.339 | Destabilizing | 0.934 | D | 0.311 | neutral | N | 0.459596589 | None | None | I |
| S/T | 0.1135 | likely_benign | 0.1002 | benign | -0.361 | Destabilizing | 0.801 | D | 0.375 | neutral | N | 0.501540906 | None | None | I |
| S/V | 0.3895 | ambiguous | 0.3296 | benign | -0.199 | Destabilizing | 0.974 | D | 0.377 | neutral | None | None | None | None | I |
| S/W | 0.5705 | likely_pathogenic | 0.5373 | ambiguous | -0.903 | Destabilizing | 0.998 | D | 0.537 | neutral | None | None | None | None | I |
| S/Y | 0.3923 | ambiguous | 0.3486 | ambiguous | -0.628 | Destabilizing | 0.991 | D | 0.371 | 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.