Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 5491 | 16696;16697;16698 | chr2:178732590;178732589;178732588 | chr2:179597317;179597316;179597315 |
| N2AB | 5174 | 15745;15746;15747 | chr2:178732590;178732589;178732588 | chr2:179597317;179597316;179597315 |
| N2A | 4247 | 12964;12965;12966 | chr2:178732590;178732589;178732588 | chr2:179597317;179597316;179597315 |
| 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 | None | None | 0.001 | N | 0.135 | 0.137 | 0.424430313326 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| V/L | rs1460594860  |
None | None | N | 0.132 | 0.134 | 0.268211541103 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.59E-05 | None | 0 | None | 0 | 0 | 0 |
| V/L | rs1460594860 |
None | None | N | 0.132 | 0.134 | 0.268211541103 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 3.861E-04 | None | 0 | 0 | 0 | 0 | 0 |
| V/L | rs1460594860 |
None | None | N | 0.132 | 0.134 | 0.268211541103 | gnomAD-4.0.0 | 6.40567E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.21412E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.0929 | likely_benign | 0.1005 | benign | -0.386 | Destabilizing | 0.001 | N | 0.135 | neutral | N | 0.477683477 | None | None | N |
| V/C | 0.578 | likely_pathogenic | 0.61 | pathogenic | -0.757 | Destabilizing | 0.883 | D | 0.361 | neutral | None | None | None | None | N |
| V/D | 0.1391 | likely_benign | 0.1743 | benign | -0.16 | Destabilizing | 0.427 | N | 0.423 | neutral | N | 0.497309388 | None | None | N |
| V/E | 0.1119 | likely_benign | 0.1412 | benign | -0.264 | Destabilizing | 0.124 | N | 0.409 | neutral | None | None | None | None | N |
| V/F | 0.1025 | likely_benign | 0.1152 | benign | -0.587 | Destabilizing | 0.427 | N | 0.377 | neutral | D | 0.52376527 | None | None | N |
| V/G | 0.1194 | likely_benign | 0.1312 | benign | -0.5 | Destabilizing | 0.096 | N | 0.394 | neutral | N | 0.498464181 | None | None | N |
| V/H | 0.2649 | likely_benign | 0.3057 | benign | -0.003 | Destabilizing | 0.958 | D | 0.405 | neutral | None | None | None | None | N |
| V/I | 0.0732 | likely_benign | 0.0797 | benign | -0.232 | Destabilizing | None | N | 0.175 | neutral | N | 0.514260353 | None | None | N |
| V/K | 0.1444 | likely_benign | 0.1838 | benign | -0.394 | Destabilizing | 0.001 | N | 0.263 | neutral | None | None | None | None | N |
| V/L | 0.1 | likely_benign | 0.1077 | benign | -0.232 | Destabilizing | None | N | 0.132 | neutral | N | 0.447285999 | None | None | N |
| V/M | 0.1103 | likely_benign | 0.1224 | benign | -0.463 | Destabilizing | 0.497 | N | 0.343 | neutral | None | None | None | None | N |
| V/N | 0.1227 | likely_benign | 0.1428 | benign | -0.214 | Destabilizing | 0.497 | N | 0.426 | neutral | None | None | None | None | N |
| V/P | 0.2325 | likely_benign | 0.2629 | benign | -0.25 | Destabilizing | 0.667 | D | 0.402 | neutral | None | None | None | None | N |
| V/Q | 0.1352 | likely_benign | 0.1532 | benign | -0.414 | Destabilizing | 0.497 | N | 0.402 | neutral | None | None | None | None | N |
| V/R | 0.1397 | likely_benign | 0.1619 | benign | 0.082 | Stabilizing | 0.331 | N | 0.422 | neutral | None | None | None | None | N |
| V/S | 0.0989 | likely_benign | 0.1088 | benign | -0.583 | Destabilizing | 0.124 | N | 0.364 | neutral | None | None | None | None | N |
| V/T | 0.1003 | likely_benign | 0.1119 | benign | -0.583 | Destabilizing | 0.002 | N | 0.131 | neutral | None | None | None | None | N |
| V/W | 0.5705 | likely_pathogenic | 0.6354 | pathogenic | -0.657 | Destabilizing | 0.958 | D | 0.449 | neutral | None | None | None | None | N |
| V/Y | 0.2944 | likely_benign | 0.3427 | ambiguous | -0.37 | Destabilizing | 0.667 | D | 0.366 | 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.