Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21008 | 63247;63248;63249 | chr2:178588703;178588702;178588701 | chr2:179453430;179453429;179453428 |
| N2AB | 19367 | 58324;58325;58326 | chr2:178588703;178588702;178588701 | chr2:179453430;179453429;179453428 |
| N2A | 18440 | 55543;55544;55545 | chr2:178588703;178588702;178588701 | chr2:179453430;179453429;179453428 |
| N2B | 11943 | 36052;36053;36054 | chr2:178588703;178588702;178588701 | chr2:179453430;179453429;179453428 |
| Novex-1 | 12068 | 36427;36428;36429 | chr2:178588703;178588702;178588701 | chr2:179453430;179453429;179453428 |
| Novex-2 | 12135 | 36628;36629;36630 | chr2:178588703;178588702;178588701 | chr2:179453430;179453429;179453428 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | None | None | None | N | 0.073 | 0.054 | 0.0551355673512 | gnomAD-4.0.0 | 6.84427E-07 | None | None | None | None | N | None | 2.99043E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/I | rs72646850  |
0.106 | None | N | 0.132 | 0.172 | None | gnomAD-2.1.1 | 9.0722E-03 | None | None | None | None | N | None | 1.98478E-03 | 1.10457E-02 | None | 1.48055E-02 | 0 | None | 7.84673E-04 | None | 2.04114E-03 | 1.39345E-02 | 1.26547E-02 |
| T/I | rs72646850 |
0.106 | None | N | 0.132 | 0.172 | None | gnomAD-3.1.2 | 9.87409E-03 | None | None | None | None | N | None | 2.80044E-03 | 1.43026E-02 | 3.28947E-03 | 1.64265E-02 | 1.9478E-04 | None | 1.9774E-03 | 0 | 1.55202E-02 | 6.20604E-04 | 1.2931E-02 |
| T/I | rs72646850 |
0.106 | None | N | 0.132 | 0.172 | None | 1000 genomes | 5.79073E-03 | None | None | None | None | N | None | 8E-04 | 1.59E-02 | None | None | 0 | 1.69E-02 | None | None | None | 0 | None |
| T/I | rs72646850 |
0.106 | None | N | 0.132 | 0.172 | None | gnomAD-4.0.0 | 1.23667E-02 | None | None | None | None | N | None | 2.25375E-03 | 1.18079E-02 | None | 1.45359E-02 | 2.23524E-05 | None | 2.34382E-03 | 7.76603E-03 | 1.48871E-02 | 1.03249E-03 | 1.26329E-02 |
| T/R | rs72646850 |
0.223 | 0.033 | N | 0.302 | 0.165 | 0.0762999501168 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| T/R | rs72646850 |
0.223 | 0.033 | N | 0.302 | 0.165 | 0.0762999501168 | gnomAD-4.0.0 | 1.36884E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.31981E-05 | 0 |
| T/S | None | None | 0.003 | N | 0.311 | 0.054 | 0.0482279557977 | gnomAD-4.0.0 | 6.84427E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52449E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0641 | likely_benign | 0.065 | benign | -0.181 | Destabilizing | None | N | 0.073 | neutral | N | 0.438788654 | None | None | N |
| T/C | 0.2706 | likely_benign | 0.2895 | benign | -0.395 | Destabilizing | 0.245 | N | 0.289 | neutral | None | None | None | None | N |
| T/D | 0.3348 | likely_benign | 0.3576 | ambiguous | 0.073 | Stabilizing | 0.044 | N | 0.36 | neutral | None | None | None | None | N |
| T/E | 0.2519 | likely_benign | 0.2751 | benign | -0.015 | Destabilizing | 0.018 | N | 0.371 | neutral | None | None | None | None | N |
| T/F | 0.1412 | likely_benign | 0.1517 | benign | -0.871 | Destabilizing | 0.044 | N | 0.323 | neutral | None | None | None | None | N |
| T/G | 0.1301 | likely_benign | 0.1293 | benign | -0.23 | Destabilizing | 0.009 | N | 0.378 | neutral | None | None | None | None | N |
| T/H | 0.1972 | likely_benign | 0.2144 | benign | -0.359 | Destabilizing | 0.497 | N | 0.291 | neutral | None | None | None | None | N |
| T/I | 0.0678 | likely_benign | 0.0925 | benign | -0.173 | Destabilizing | None | N | 0.132 | neutral | N | 0.423320556 | None | None | N |
| T/K | 0.1849 | likely_benign | 0.2031 | benign | -0.255 | Destabilizing | 0.014 | N | 0.377 | neutral | N | 0.420394894 | None | None | N |
| T/L | 0.0501 | likely_benign | 0.0498 | benign | -0.173 | Destabilizing | None | N | 0.13 | neutral | None | None | None | None | N |
| T/M | 0.0593 | likely_benign | 0.0644 | benign | -0.233 | Destabilizing | 0.044 | N | 0.323 | neutral | None | None | None | None | N |
| T/N | 0.0842 | likely_benign | 0.0909 | benign | -0.085 | Destabilizing | 0.085 | N | 0.261 | neutral | None | None | None | None | N |
| T/P | 0.0768 | likely_benign | 0.0722 | benign | -0.152 | Destabilizing | 0.033 | N | 0.329 | neutral | N | 0.443829114 | None | None | N |
| T/Q | 0.1631 | likely_benign | 0.1793 | benign | -0.263 | Destabilizing | 0.085 | N | 0.322 | neutral | None | None | None | None | N |
| T/R | 0.1717 | likely_benign | 0.1951 | benign | 0.017 | Stabilizing | 0.033 | N | 0.302 | neutral | N | 0.429881169 | None | None | N |
| T/S | 0.079 | likely_benign | 0.0791 | benign | -0.254 | Destabilizing | 0.003 | N | 0.311 | neutral | N | 0.384396809 | None | None | N |
| T/V | 0.0609 | likely_benign | 0.0692 | benign | -0.152 | Destabilizing | None | N | 0.066 | neutral | None | None | None | None | N |
| T/W | 0.4184 | ambiguous | 0.4512 | ambiguous | -0.971 | Destabilizing | 0.788 | D | 0.295 | neutral | None | None | None | None | N |
| T/Y | 0.1897 | likely_benign | 0.2154 | benign | -0.64 | Destabilizing | 0.085 | N | 0.296 | 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.