Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20778 | 62557;62558;62559 | chr2:178589393;178589392;178589391 | chr2:179454120;179454119;179454118 |
| N2AB | 19137 | 57634;57635;57636 | chr2:178589393;178589392;178589391 | chr2:179454120;179454119;179454118 |
| N2A | 18210 | 54853;54854;54855 | chr2:178589393;178589392;178589391 | chr2:179454120;179454119;179454118 |
| N2B | 11713 | 35362;35363;35364 | chr2:178589393;178589392;178589391 | chr2:179454120;179454119;179454118 |
| Novex-1 | 11838 | 35737;35738;35739 | chr2:178589393;178589392;178589391 | chr2:179454120;179454119;179454118 |
| Novex-2 | 11905 | 35938;35939;35940 | chr2:178589393;178589392;178589391 | chr2:179454120;179454119;179454118 |
| 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/F | rs754672686  |
-0.906 | 0.966 | D | 0.488 | 0.276 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.64E-05 | 0 | 0 |
| V/F | rs754672686 |
-0.906 | 0.966 | D | 0.488 | 0.276 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/F | rs754672686 |
-0.906 | 0.966 | D | 0.488 | 0.276 | None | gnomAD-4.0.0 | 1.23972E-06 | None | None | None | None | N | None | 1.33561E-05 | 0 | None | 0 | 0 | None | 1.5626E-05 | 0 | 0 | 0 | 0 |
| V/I | None | None | 0.625 | D | 0.445 | 0.108 | 0.588051273532 | gnomAD-4.0.0 | 6.84334E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99551E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1954 | likely_benign | 0.2051 | benign | -0.569 | Destabilizing | 0.022 | N | 0.105 | neutral | N | 0.486727035 | None | None | N |
| V/C | 0.6772 | likely_pathogenic | 0.7511 | pathogenic | -0.716 | Destabilizing | 0.998 | D | 0.455 | neutral | None | None | None | None | N |
| V/D | 0.3939 | ambiguous | 0.4438 | ambiguous | -0.05 | Destabilizing | 0.934 | D | 0.597 | neutral | N | 0.428273377 | None | None | N |
| V/E | 0.3221 | likely_benign | 0.3467 | ambiguous | -0.136 | Destabilizing | 0.842 | D | 0.518 | neutral | None | None | None | None | N |
| V/F | 0.1855 | likely_benign | 0.187 | benign | -0.622 | Destabilizing | 0.966 | D | 0.488 | neutral | D | 0.527440294 | None | None | N |
| V/G | 0.2317 | likely_benign | 0.2313 | benign | -0.745 | Destabilizing | 0.801 | D | 0.548 | neutral | N | 0.410826554 | None | None | N |
| V/H | 0.5787 | likely_pathogenic | 0.6284 | pathogenic | -0.287 | Destabilizing | 0.998 | D | 0.589 | neutral | None | None | None | None | N |
| V/I | 0.0708 | likely_benign | 0.0754 | benign | -0.245 | Destabilizing | 0.625 | D | 0.445 | neutral | D | 0.527266935 | None | None | N |
| V/K | 0.3945 | ambiguous | 0.428 | ambiguous | -0.478 | Destabilizing | 0.842 | D | 0.521 | neutral | None | None | None | None | N |
| V/L | 0.1932 | likely_benign | 0.2081 | benign | -0.245 | Destabilizing | 0.454 | N | 0.405 | neutral | N | 0.485612314 | None | None | N |
| V/M | 0.1429 | likely_benign | 0.1555 | benign | -0.347 | Destabilizing | 0.991 | D | 0.427 | neutral | None | None | None | None | N |
| V/N | 0.2156 | likely_benign | 0.247 | benign | -0.254 | Destabilizing | 0.949 | D | 0.597 | neutral | None | None | None | None | N |
| V/P | 0.524 | ambiguous | 0.5387 | ambiguous | -0.317 | Destabilizing | 0.974 | D | 0.547 | neutral | None | None | None | None | N |
| V/Q | 0.314 | likely_benign | 0.3419 | ambiguous | -0.446 | Destabilizing | 0.974 | D | 0.574 | neutral | None | None | None | None | N |
| V/R | 0.4179 | ambiguous | 0.4382 | ambiguous | -0.022 | Destabilizing | 0.974 | D | 0.607 | neutral | None | None | None | None | N |
| V/S | 0.1936 | likely_benign | 0.2117 | benign | -0.705 | Destabilizing | 0.728 | D | 0.48 | neutral | None | None | None | None | N |
| V/T | 0.1489 | likely_benign | 0.1707 | benign | -0.68 | Destabilizing | 0.01 | N | 0.104 | neutral | None | None | None | None | N |
| V/W | 0.8218 | likely_pathogenic | 0.8377 | pathogenic | -0.712 | Destabilizing | 0.998 | D | 0.633 | neutral | None | None | None | None | N |
| V/Y | 0.5189 | ambiguous | 0.5669 | pathogenic | -0.409 | Destabilizing | 0.991 | D | 0.496 | 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.