Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25760 | 77503;77504;77505 | chr2:178568854;178568853;178568852 | chr2:179433581;179433580;179433579 |
| N2AB | 24119 | 72580;72581;72582 | chr2:178568854;178568853;178568852 | chr2:179433581;179433580;179433579 |
| N2A | 23192 | 69799;69800;69801 | chr2:178568854;178568853;178568852 | chr2:179433581;179433580;179433579 |
| N2B | 16695 | 50308;50309;50310 | chr2:178568854;178568853;178568852 | chr2:179433581;179433580;179433579 |
| Novex-1 | 16820 | 50683;50684;50685 | chr2:178568854;178568853;178568852 | chr2:179433581;179433580;179433579 |
| Novex-2 | 16887 | 50884;50885;50886 | chr2:178568854;178568853;178568852 | chr2:179433581;179433580;179433579 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/K | None | None | 0.892 | N | 0.496 | 0.232 | 0.126345400529 | gnomAD-4.0.0 | 6.84495E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99604E-07 | 0 | 0 |
| N/S | rs3813246  |
0.257 | 0.243 | N | 0.283 | 0.116 | None | gnomAD-2.1.1 | 2.57166E-02 | None | None | None | None | N | None | 4.83791E-03 | 3.34768E-02 | None | 1.4612E-02 | 6.13756E-02 | None | 6.04891E-03 | None | 4.81879E-02 | 2.33044E-02 | 2.64565E-02 |
| N/S | rs3813246 |
0.257 | 0.243 | N | 0.283 | 0.116 | None | gnomAD-3.1.2 | 2.01989E-02 | None | None | None | None | N | None | 4.44166E-03 | 2.18619E-02 | 3.07018E-02 | 1.90202E-02 | 6.1339E-02 | None | 4.42036E-02 | 6.32911E-03 | 2.34033E-02 | 8.28157E-03 | 1.95985E-02 |
| N/S | rs3813246 |
0.257 | 0.243 | N | 0.283 | 0.116 | None | 1000 genomes | 2.23642E-02 | None | None | None | None | N | None | 8E-04 | 2.45E-02 | None | None | 6.05E-02 | 2.68E-02 | None | None | None | 6.1E-03 | None |
| N/S | rs3813246 |
0.257 | 0.243 | N | 0.283 | 0.116 | None | gnomAD-4.0.0 | 2.28761E-02 | None | None | None | None | N | None | 4.25367E-03 | 2.93706E-02 | None | 1.48719E-02 | 6.31891E-02 | None | 4.76071E-02 | 9.74884E-03 | 2.24335E-02 | 6.7762E-03 | 2.16459E-02 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.2207 | likely_benign | 0.2019 | benign | -0.147 | Destabilizing | 0.845 | D | 0.48 | neutral | None | None | None | None | N |
| N/C | 0.4032 | ambiguous | 0.3643 | ambiguous | 0.242 | Stabilizing | 0.999 | D | 0.646 | neutral | None | None | None | None | N |
| N/D | 0.1319 | likely_benign | 0.1235 | benign | 0.123 | Stabilizing | 0.025 | N | 0.227 | neutral | N | 0.444213117 | None | None | N |
| N/E | 0.4348 | ambiguous | 0.3902 | ambiguous | 0.059 | Stabilizing | 0.845 | D | 0.476 | neutral | None | None | None | None | N |
| N/F | 0.6622 | likely_pathogenic | 0.6438 | pathogenic | -0.738 | Destabilizing | 0.996 | D | 0.63 | neutral | None | None | None | None | N |
| N/G | 0.1901 | likely_benign | 0.1725 | benign | -0.243 | Destabilizing | 0.916 | D | 0.48 | neutral | None | None | None | None | N |
| N/H | 0.1244 | likely_benign | 0.1124 | benign | -0.279 | Destabilizing | 0.994 | D | 0.529 | neutral | N | 0.47261346 | None | None | N |
| N/I | 0.4866 | ambiguous | 0.4635 | ambiguous | 0.007 | Stabilizing | 0.983 | D | 0.626 | neutral | N | 0.51122828 | None | None | N |
| N/K | 0.3734 | ambiguous | 0.3406 | ambiguous | 0.17 | Stabilizing | 0.892 | D | 0.496 | neutral | N | 0.465225894 | None | None | N |
| N/L | 0.389 | ambiguous | 0.3653 | ambiguous | 0.007 | Stabilizing | 0.987 | D | 0.576 | neutral | None | None | None | None | N |
| N/M | 0.4906 | ambiguous | 0.4591 | ambiguous | 0.18 | Stabilizing | 0.999 | D | 0.563 | neutral | None | None | None | None | N |
| N/P | 0.701 | likely_pathogenic | 0.674 | pathogenic | -0.021 | Destabilizing | 0.987 | D | 0.576 | neutral | None | None | None | None | N |
| N/Q | 0.3667 | ambiguous | 0.3256 | benign | -0.222 | Destabilizing | 0.987 | D | 0.517 | neutral | None | None | None | None | N |
| N/R | 0.4228 | ambiguous | 0.3848 | ambiguous | 0.237 | Stabilizing | 0.987 | D | 0.513 | neutral | None | None | None | None | N |
| N/S | 0.0789 | likely_benign | 0.077 | benign | 0.009 | Stabilizing | 0.243 | N | 0.283 | neutral | N | 0.487217319 | None | None | N |
| N/T | 0.1695 | likely_benign | 0.1578 | benign | 0.062 | Stabilizing | 0.805 | D | 0.482 | neutral | N | 0.474677375 | None | None | N |
| N/V | 0.4018 | ambiguous | 0.3774 | ambiguous | -0.021 | Destabilizing | 0.987 | D | 0.616 | neutral | None | None | None | None | N |
| N/W | 0.86 | likely_pathogenic | 0.8396 | pathogenic | -0.847 | Destabilizing | 0.999 | D | 0.681 | prob.neutral | None | None | None | None | N |
| N/Y | 0.2534 | likely_benign | 0.241 | benign | -0.527 | Destabilizing | 0.994 | D | 0.576 | neutral | N | 0.499618485 | 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.