Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 8749 | 26470;26471;26472 | chr2:178714529;178714528;178714527 | chr2:179579256;179579255;179579254 |
| N2AB | 8432 | 25519;25520;25521 | chr2:178714529;178714528;178714527 | chr2:179579256;179579255;179579254 |
| N2A | 7505 | 22738;22739;22740 | chr2:178714529;178714528;178714527 | chr2:179579256;179579255;179579254 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs770874023  |
-0.212 | None | N | 0.139 | 0.052 | None | gnomAD-2.1.1 | 3.63E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 9.39E-05 | 6.23E-05 | 0 |
| V/A | rs770874023 |
-0.212 | None | N | 0.139 | 0.052 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 9.49367E-03 | 1.47E-05 | 0 | 0 |
| V/A | rs770874023 |
-0.212 | None | N | 0.139 | 0.052 | None | gnomAD-4.0.0 | 2.72796E-05 | None | None | None | None | I | None | 0 | 1.66789E-05 | None | 0 | 0 | None | 3.13509E-05 | 6.6072E-04 | 2.45875E-05 | 3.29823E-05 | 8.00743E-05 |
| V/I | rs16866457 |
0.002 | None | N | 0.149 | 0.042 | None | gnomAD-2.1.1 | 5.20363E-03 | None | None | None | None | I | None | 4.10006E-02 | 1.61803E-03 | None | 3.10138E-02 | 0 | None | 9.84E-05 | None | 0 | 4.69807E-04 | 3.24767E-03 |
| V/I | rs16866457 |
0.002 | None | N | 0.149 | 0.042 | None | gnomAD-3.1.2 | 1.249E-02 | None | None | None | None | I | None | 4.10105E-02 | 3.60419E-03 | 0 | 2.94118E-02 | 0 | None | 0 | 0 | 3.82353E-04 | 0 | 8.61244E-03 |
| V/I | rs16866457 |
0.002 | None | N | 0.149 | 0.042 | None | 1000 genomes | 1.61741E-02 | None | None | None | None | I | None | 5.82E-02 | 5.8E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| V/I | rs16866457 |
0.002 | None | N | 0.149 | 0.042 | None | gnomAD-4.0.0 | 3.01617E-03 | None | None | None | None | I | None | 4.22047E-02 | 2.60156E-03 | None | 3.07068E-02 | 0 | None | 0 | 1.32188E-03 | 2.50112E-04 | 8.7943E-05 | 5.22084E-03 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.0653 | likely_benign | 0.0656 | benign | -1.12 | Destabilizing | None | N | 0.139 | neutral | N | 0.483875078 | None | None | I |
| V/C | 0.6028 | likely_pathogenic | 0.6304 | pathogenic | -0.771 | Destabilizing | 0.129 | N | 0.329 | neutral | None | None | None | None | I |
| V/D | 0.2133 | likely_benign | 0.2364 | benign | -0.884 | Destabilizing | 0.119 | N | 0.409 | neutral | N | 0.478221329 | None | None | I |
| V/E | 0.1625 | likely_benign | 0.1769 | benign | -0.927 | Destabilizing | 0.008 | N | 0.398 | neutral | None | None | None | None | I |
| V/F | 0.117 | likely_benign | 0.1347 | benign | -0.916 | Destabilizing | 0.206 | N | 0.365 | neutral | N | 0.500271643 | None | None | I |
| V/G | 0.1332 | likely_benign | 0.1544 | benign | -1.374 | Destabilizing | 0.025 | N | 0.435 | neutral | N | 0.500525132 | None | None | I |
| V/H | 0.3682 | ambiguous | 0.4144 | ambiguous | -0.86 | Destabilizing | 0.692 | D | 0.358 | neutral | None | None | None | None | I |
| V/I | 0.0658 | likely_benign | 0.0696 | benign | -0.548 | Destabilizing | None | N | 0.149 | neutral | N | 0.493073351 | None | None | I |
| V/K | 0.2039 | likely_benign | 0.2457 | benign | -1.042 | Destabilizing | 0.018 | N | 0.407 | neutral | None | None | None | None | I |
| V/L | 0.1145 | likely_benign | 0.1273 | benign | -0.548 | Destabilizing | None | N | 0.103 | neutral | N | 0.483760435 | None | None | I |
| V/M | 0.1016 | likely_benign | 0.114 | benign | -0.451 | Destabilizing | 0.088 | N | 0.307 | neutral | None | None | None | None | I |
| V/N | 0.1685 | likely_benign | 0.1889 | benign | -0.781 | Destabilizing | 0.009 | N | 0.408 | neutral | None | None | None | None | I |
| V/P | 0.2445 | likely_benign | 0.2487 | benign | -0.702 | Destabilizing | 0.019 | N | 0.381 | neutral | None | None | None | None | I |
| V/Q | 0.2096 | likely_benign | 0.2333 | benign | -0.984 | Destabilizing | 0.083 | N | 0.365 | neutral | None | None | None | None | I |
| V/R | 0.1688 | likely_benign | 0.2017 | benign | -0.467 | Destabilizing | 0.119 | N | 0.401 | neutral | None | None | None | None | I |
| V/S | 0.096 | likely_benign | 0.0978 | benign | -1.23 | Destabilizing | 0.001 | N | 0.298 | neutral | None | None | None | None | I |
| V/T | 0.0852 | likely_benign | 0.0881 | benign | -1.171 | Destabilizing | None | N | 0.225 | neutral | None | None | None | None | I |
| V/W | 0.5901 | likely_pathogenic | 0.6712 | pathogenic | -1.057 | Destabilizing | 0.894 | D | 0.419 | neutral | None | None | None | None | I |
| V/Y | 0.3763 | ambiguous | 0.4155 | ambiguous | -0.784 | Destabilizing | 0.215 | N | 0.326 | 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.