Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18382 | 55369;55370;55371 | chr2:178602127;178602126;178602125 | chr2:179466854;179466853;179466852 |
| N2AB | 16741 | 50446;50447;50448 | chr2:178602127;178602126;178602125 | chr2:179466854;179466853;179466852 |
| N2A | 15814 | 47665;47666;47667 | chr2:178602127;178602126;178602125 | chr2:179466854;179466853;179466852 |
| N2B | 9317 | 28174;28175;28176 | chr2:178602127;178602126;178602125 | chr2:179466854;179466853;179466852 |
| Novex-1 | 9442 | 28549;28550;28551 | chr2:178602127;178602126;178602125 | chr2:179466854;179466853;179466852 |
| Novex-2 | 9509 | 28750;28751;28752 | chr2:178602127;178602126;178602125 | chr2:179466854;179466853;179466852 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | None | None | 0.801 | N | 0.465 | 0.356 | 0.664688822591 | gnomAD-4.0.0 | 6.87451E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.02032E-07 | 0 | 0 |
| I/V | rs1233345100  |
-0.59 | 0.005 | N | 0.188 | 0.064 | 0.346544149963 | gnomAD-2.1.1 | 8.24E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.68E-05 | None | 0 | None | 0 | 9.05E-06 | 0 |
| I/V | rs1233345100 |
-0.59 | 0.005 | N | 0.188 | 0.064 | 0.346544149963 | gnomAD-4.0.0 | 3.43698E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.0674E-05 | None | 0 | 0 | 9.02017E-07 | 1.17805E-05 | 1.66456E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.2949 | likely_benign | 0.2392 | benign | -0.622 | Destabilizing | 0.525 | D | 0.445 | neutral | None | None | None | None | I |
| I/C | 0.7871 | likely_pathogenic | 0.7213 | pathogenic | -0.706 | Destabilizing | 0.998 | D | 0.475 | neutral | None | None | None | None | I |
| I/D | 0.8645 | likely_pathogenic | 0.8082 | pathogenic | -0.178 | Destabilizing | 0.991 | D | 0.471 | neutral | None | None | None | None | I |
| I/E | 0.7961 | likely_pathogenic | 0.7285 | pathogenic | -0.251 | Destabilizing | 0.974 | D | 0.471 | neutral | None | None | None | None | I |
| I/F | 0.2753 | likely_benign | 0.2369 | benign | -0.586 | Destabilizing | 0.934 | D | 0.463 | neutral | N | 0.507814383 | None | None | I |
| I/G | 0.7779 | likely_pathogenic | 0.697 | pathogenic | -0.799 | Destabilizing | 0.974 | D | 0.463 | neutral | None | None | None | None | I |
| I/H | 0.8069 | likely_pathogenic | 0.7337 | pathogenic | -0.147 | Destabilizing | 0.998 | D | 0.459 | neutral | None | None | None | None | I |
| I/K | 0.6612 | likely_pathogenic | 0.5804 | pathogenic | -0.421 | Destabilizing | 0.974 | D | 0.475 | neutral | None | None | None | None | I |
| I/L | 0.1406 | likely_benign | 0.1189 | benign | -0.267 | Destabilizing | 0.005 | N | 0.177 | neutral | N | 0.505387366 | None | None | I |
| I/M | 0.1271 | likely_benign | 0.1085 | benign | -0.468 | Destabilizing | 0.934 | D | 0.491 | neutral | N | 0.507641025 | None | None | I |
| I/N | 0.5767 | likely_pathogenic | 0.468 | ambiguous | -0.221 | Destabilizing | 0.989 | D | 0.457 | neutral | N | 0.5081611 | None | None | I |
| I/P | 0.7097 | likely_pathogenic | 0.6546 | pathogenic | -0.353 | Destabilizing | 0.991 | D | 0.467 | neutral | None | None | None | None | I |
| I/Q | 0.7293 | likely_pathogenic | 0.6372 | pathogenic | -0.399 | Destabilizing | 0.991 | D | 0.456 | neutral | None | None | None | None | I |
| I/R | 0.5785 | likely_pathogenic | 0.5051 | ambiguous | 0.062 | Stabilizing | 0.974 | D | 0.458 | neutral | None | None | None | None | I |
| I/S | 0.4303 | ambiguous | 0.4326 | ambiguous | -0.67 | Destabilizing | 0.966 | D | 0.461 | neutral | N | 0.507814383 | None | None | I |
| I/T | 0.1517 | likely_benign | 0.1261 | benign | -0.631 | Destabilizing | 0.801 | D | 0.465 | neutral | N | 0.507467666 | None | None | I |
| I/V | 0.0895 | likely_benign | 0.0791 | benign | -0.353 | Destabilizing | 0.005 | N | 0.188 | neutral | N | 0.439367444 | None | None | I |
| I/W | 0.8603 | likely_pathogenic | 0.8224 | pathogenic | -0.622 | Destabilizing | 0.998 | D | 0.499 | neutral | None | None | None | None | I |
| I/Y | 0.7588 | likely_pathogenic | 0.7106 | pathogenic | -0.373 | Destabilizing | 0.974 | D | 0.478 | 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.