Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26989 | 81190;81191;81192 | chr2:178565167;178565166;178565165 | chr2:179429894;179429893;179429892 |
| N2AB | 25348 | 76267;76268;76269 | chr2:178565167;178565166;178565165 | chr2:179429894;179429893;179429892 |
| N2A | 24421 | 73486;73487;73488 | chr2:178565167;178565166;178565165 | chr2:179429894;179429893;179429892 |
| N2B | 17924 | 53995;53996;53997 | chr2:178565167;178565166;178565165 | chr2:179429894;179429893;179429892 |
| Novex-1 | 18049 | 54370;54371;54372 | chr2:178565167;178565166;178565165 | chr2:179429894;179429893;179429892 |
| Novex-2 | 18116 | 54571;54572;54573 | chr2:178565167;178565166;178565165 | chr2:179429894;179429893;179429892 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/I | rs1348393968  |
None | 0.324 | N | 0.49 | 0.229 | 0.339555952218 | gnomAD-4.0.0 | 6.00161E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.56251E-06 | 0 | 0 |
| F/S | rs1351288093 |
None | 0.006 | N | 0.398 | 0.193 | 0.325533332567 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 2.88184E-04 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| F/S | rs1351288093 |
None | 0.006 | N | 0.398 | 0.193 | 0.325533332567 | gnomAD-4.0.0 | 2.56344E-06 | None | None | None | None | N | None | 0 | 0 | None | 4.09366E-05 | 0 | None | 0 | 0 | 0 | 1.34095E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.3253 | likely_benign | 0.358 | ambiguous | -2.758 | Highly Destabilizing | 0.116 | N | 0.461 | neutral | None | None | None | None | N |
| F/C | 0.2095 | likely_benign | 0.2306 | benign | -1.469 | Destabilizing | 0.975 | D | 0.603 | neutral | N | 0.439788732 | None | None | N |
| F/D | 0.7315 | likely_pathogenic | 0.7272 | pathogenic | -2.184 | Highly Destabilizing | 0.69 | D | 0.652 | neutral | None | None | None | None | N |
| F/E | 0.8288 | likely_pathogenic | 0.8251 | pathogenic | -2.093 | Highly Destabilizing | 0.388 | N | 0.652 | neutral | None | None | None | None | N |
| F/G | 0.6106 | likely_pathogenic | 0.627 | pathogenic | -3.095 | Highly Destabilizing | 0.241 | N | 0.585 | neutral | None | None | None | None | N |
| F/H | 0.3528 | ambiguous | 0.3585 | ambiguous | -1.323 | Destabilizing | 0.69 | D | 0.559 | neutral | None | None | None | None | N |
| F/I | 0.3204 | likely_benign | 0.3186 | benign | -1.71 | Destabilizing | 0.324 | N | 0.49 | neutral | N | 0.477229612 | None | None | N |
| F/K | 0.8513 | likely_pathogenic | 0.8412 | pathogenic | -1.616 | Destabilizing | 0.388 | N | 0.649 | neutral | None | None | None | None | N |
| F/L | 0.8602 | likely_pathogenic | 0.8509 | pathogenic | -1.71 | Destabilizing | 0.09 | N | 0.425 | neutral | N | 0.487830608 | None | None | N |
| F/M | 0.4257 | ambiguous | 0.4273 | ambiguous | -1.311 | Destabilizing | 0.932 | D | 0.481 | neutral | None | None | None | None | N |
| F/N | 0.3798 | ambiguous | 0.3645 | ambiguous | -1.688 | Destabilizing | 0.69 | D | 0.658 | neutral | None | None | None | None | N |
| F/P | 0.9981 | likely_pathogenic | 0.9982 | pathogenic | -2.059 | Highly Destabilizing | 0.818 | D | 0.649 | neutral | None | None | None | None | N |
| F/Q | 0.716 | likely_pathogenic | 0.708 | pathogenic | -1.866 | Destabilizing | 0.818 | D | 0.652 | neutral | None | None | None | None | N |
| F/R | 0.7492 | likely_pathogenic | 0.7506 | pathogenic | -0.79 | Destabilizing | 0.69 | D | 0.655 | neutral | None | None | None | None | N |
| F/S | 0.1654 | likely_benign | 0.1838 | benign | -2.417 | Highly Destabilizing | 0.006 | N | 0.398 | neutral | N | 0.282608088 | None | None | N |
| F/T | 0.2383 | likely_benign | 0.2551 | benign | -2.24 | Highly Destabilizing | 0.241 | N | 0.567 | neutral | None | None | None | None | N |
| F/V | 0.25 | likely_benign | 0.2419 | benign | -2.059 | Highly Destabilizing | 0.324 | N | 0.515 | neutral | N | 0.436940428 | None | None | N |
| F/W | 0.5471 | ambiguous | 0.5404 | ambiguous | -0.726 | Destabilizing | 0.818 | D | 0.467 | neutral | None | None | None | None | N |
| F/Y | 0.1103 | likely_benign | 0.1015 | benign | -0.966 | Destabilizing | None | N | 0.101 | neutral | N | 0.388013117 | 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.