Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 5031 | 15316;15317;15318 | chr2:178734833;178734832;178734831 | chr2:179599560;179599559;179599558 |
| N2AB | 4714 | 14365;14366;14367 | chr2:178734833;178734832;178734831 | chr2:179599560;179599559;179599558 |
| N2A | 3787 | 11584;11585;11586 | chr2:178734833;178734832;178734831 | chr2:179599560;179599559;179599558 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs1239777211  |
-0.043 | 0.196 | N | 0.356 | 0.233 | 0.585321940634 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| Y/C | rs1239777211 |
-0.043 | 0.196 | N | 0.356 | 0.233 | 0.585321940634 | gnomAD-4.0.0 | 1.59134E-06 | None | None | None | None | N | None | 0 | 2.28676E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| Y/D | rs879023034 |
0.473 | 0.003 | N | 0.333 | 0.106 | None | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | N | None | 4.13E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.56E-05 | 0 |
| Y/D | rs879023034 |
0.473 | 0.003 | N | 0.333 | 0.106 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 7.23E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| Y/D | rs879023034 |
0.473 | 0.003 | N | 0.333 | 0.106 | None | gnomAD-4.0.0 | 1.2394E-05 | None | None | None | None | N | None | 4.00363E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.44097E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.096 | likely_benign | 0.1121 | benign | -1.209 | Destabilizing | 0.001 | N | 0.187 | neutral | None | None | None | None | N |
| Y/C | 0.0778 | likely_benign | 0.093 | benign | -0.098 | Destabilizing | 0.196 | N | 0.356 | neutral | N | 0.50733238 | None | None | N |
| Y/D | 0.1355 | likely_benign | 0.1351 | benign | 0.273 | Stabilizing | 0.003 | N | 0.333 | neutral | N | 0.465633107 | None | None | N |
| Y/E | 0.3161 | likely_benign | 0.3296 | benign | 0.283 | Stabilizing | 0.004 | N | 0.287 | neutral | None | None | None | None | N |
| Y/F | 0.0672 | likely_benign | 0.073 | benign | -0.559 | Destabilizing | 0.028 | N | 0.285 | neutral | N | 0.455167949 | None | None | N |
| Y/G | 0.1412 | likely_benign | 0.1445 | benign | -1.452 | Destabilizing | 0.002 | N | 0.286 | neutral | None | None | None | None | N |
| Y/H | 0.0974 | likely_benign | 0.1031 | benign | -0.217 | Destabilizing | 0.196 | N | 0.329 | neutral | N | 0.449607746 | None | None | N |
| Y/I | 0.1636 | likely_benign | 0.1772 | benign | -0.541 | Destabilizing | 0.018 | N | 0.31 | neutral | None | None | None | None | N |
| Y/K | 0.3404 | ambiguous | 0.3258 | benign | -0.257 | Destabilizing | 0.004 | N | 0.283 | neutral | None | None | None | None | N |
| Y/L | 0.1768 | likely_benign | 0.2036 | benign | -0.541 | Destabilizing | 0.008 | N | 0.206 | neutral | None | None | None | None | N |
| Y/M | 0.236 | likely_benign | 0.2584 | benign | -0.326 | Destabilizing | 0.497 | N | 0.32 | neutral | None | None | None | None | N |
| Y/N | 0.0635 | likely_benign | 0.066 | benign | -0.441 | Destabilizing | 0.003 | N | 0.285 | neutral | N | 0.461367235 | None | None | N |
| Y/P | 0.8434 | likely_pathogenic | 0.8593 | pathogenic | -0.749 | Destabilizing | 0.018 | N | 0.372 | neutral | None | None | None | None | N |
| Y/Q | 0.2033 | likely_benign | 0.2258 | benign | -0.4 | Destabilizing | 0.018 | N | 0.346 | neutral | None | None | None | None | N |
| Y/R | 0.234 | likely_benign | 0.2332 | benign | 0.07 | Stabilizing | 0.018 | N | 0.357 | neutral | None | None | None | None | N |
| Y/S | 0.0395 | likely_benign | 0.0448 | benign | -0.862 | Destabilizing | None | N | 0.124 | neutral | N | 0.338957077 | None | None | N |
| Y/T | 0.0775 | likely_benign | 0.0835 | benign | -0.757 | Destabilizing | None | N | 0.109 | neutral | None | None | None | None | N |
| Y/V | 0.1329 | likely_benign | 0.1448 | benign | -0.749 | Destabilizing | 0.008 | N | 0.252 | neutral | None | None | None | None | N |
| Y/W | 0.2986 | likely_benign | 0.3131 | benign | -0.514 | Destabilizing | 0.497 | N | 0.315 | 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.