Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15810 | 47653;47654;47655 | chr2:178617923;178617922;178617921 | chr2:179482650;179482649;179482648 |
| N2AB | 14169 | 42730;42731;42732 | chr2:178617923;178617922;178617921 | chr2:179482650;179482649;179482648 |
| N2A | 13242 | 39949;39950;39951 | chr2:178617923;178617922;178617921 | chr2:179482650;179482649;179482648 |
| N2B | 6745 | 20458;20459;20460 | chr2:178617923;178617922;178617921 | chr2:179482650;179482649;179482648 |
| Novex-1 | 6870 | 20833;20834;20835 | chr2:178617923;178617922;178617921 | chr2:179482650;179482649;179482648 |
| Novex-2 | 6937 | 21034;21035;21036 | chr2:178617923;178617922;178617921 | chr2:179482650;179482649;179482648 |
| 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/I | rs748816848  |
0.083 | 0.012 | N | 0.276 | 0.143 | None | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 9.8E-05 | None | 0 | 8.91E-06 | 0 |
| T/I | rs748816848 |
0.083 | 0.012 | N | 0.276 | 0.143 | None | gnomAD-4.0.0 | 1.09536E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59969E-06 | 1.27563E-04 | 1.65854E-05 |
| T/P | None | None | 0.989 | N | 0.578 | 0.371 | 0.393927044628 | gnomAD-4.0.0 | 1.36919E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.31927E-05 | 0 |
| T/S | None | None | 0.891 | N | 0.366 | 0.116 | 0.183819452728 | gnomAD-4.0.0 | 6.84598E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99922E-07 | 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 | 0.0895 | likely_benign | 0.0864 | benign | -0.685 | Destabilizing | 0.625 | D | 0.351 | neutral | N | 0.476396356 | None | None | N |
| T/C | 0.4852 | ambiguous | 0.4026 | ambiguous | -0.391 | Destabilizing | 0.998 | D | 0.513 | neutral | None | None | None | None | N |
| T/D | 0.4 | ambiguous | 0.3876 | ambiguous | -0.175 | Destabilizing | 0.991 | D | 0.584 | neutral | None | None | None | None | N |
| T/E | 0.2674 | likely_benign | 0.257 | benign | -0.208 | Destabilizing | 0.971 | D | 0.567 | neutral | None | None | None | None | N |
| T/F | 0.259 | likely_benign | 0.2333 | benign | -0.876 | Destabilizing | 0.949 | D | 0.599 | neutral | None | None | None | None | N |
| T/G | 0.3215 | likely_benign | 0.2964 | benign | -0.904 | Destabilizing | 0.971 | D | 0.573 | neutral | None | None | None | None | N |
| T/H | 0.2693 | likely_benign | 0.2435 | benign | -1.232 | Destabilizing | 0.998 | D | 0.559 | neutral | None | None | None | None | N |
| T/I | 0.1427 | likely_benign | 0.1297 | benign | -0.204 | Destabilizing | 0.012 | N | 0.276 | neutral | N | 0.475761048 | None | None | N |
| T/K | 0.2378 | likely_benign | 0.2338 | benign | -0.744 | Destabilizing | 0.915 | D | 0.569 | neutral | None | None | None | None | N |
| T/L | 0.107 | likely_benign | 0.0999 | benign | -0.204 | Destabilizing | 0.007 | N | 0.211 | neutral | None | None | None | None | N |
| T/M | 0.0844 | likely_benign | 0.0829 | benign | 0.091 | Stabilizing | 0.949 | D | 0.555 | neutral | None | None | None | None | N |
| T/N | 0.1166 | likely_benign | 0.1099 | benign | -0.576 | Destabilizing | 0.989 | D | 0.502 | neutral | N | 0.472051747 | None | None | N |
| T/P | 0.2468 | likely_benign | 0.2223 | benign | -0.333 | Destabilizing | 0.989 | D | 0.578 | neutral | N | 0.483527918 | None | None | N |
| T/Q | 0.2272 | likely_benign | 0.2147 | benign | -0.783 | Destabilizing | 0.991 | D | 0.555 | neutral | None | None | None | None | N |
| T/R | 0.2104 | likely_benign | 0.2062 | benign | -0.467 | Destabilizing | 0.991 | D | 0.564 | neutral | None | None | None | None | N |
| T/S | 0.1277 | likely_benign | 0.1185 | benign | -0.814 | Destabilizing | 0.891 | D | 0.366 | neutral | N | 0.467327855 | None | None | N |
| T/V | 0.1131 | likely_benign | 0.1036 | benign | -0.333 | Destabilizing | 0.029 | N | 0.132 | neutral | None | None | None | None | N |
| T/W | 0.6126 | likely_pathogenic | 0.5751 | pathogenic | -0.827 | Destabilizing | 0.998 | D | 0.599 | neutral | None | None | None | None | N |
| T/Y | 0.2929 | likely_benign | 0.2612 | benign | -0.6 | Destabilizing | 0.991 | D | 0.603 | 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.