Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27781 | 83566;83567;83568 | chr2:178562791;178562790;178562789 | chr2:179427518;179427517;179427516 |
| N2AB | 26140 | 78643;78644;78645 | chr2:178562791;178562790;178562789 | chr2:179427518;179427517;179427516 |
| N2A | 25213 | 75862;75863;75864 | chr2:178562791;178562790;178562789 | chr2:179427518;179427517;179427516 |
| N2B | 18716 | 56371;56372;56373 | chr2:178562791;178562790;178562789 | chr2:179427518;179427517;179427516 |
| Novex-1 | 18841 | 56746;56747;56748 | chr2:178562791;178562790;178562789 | chr2:179427518;179427517;179427516 |
| Novex-2 | 18908 | 56947;56948;56949 | chr2:178562791;178562790;178562789 | chr2:179427518;179427517;179427516 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/N | rs773517655  |
-0.502 | 0.003 | N | 0.052 | 0.08 | 0.229264304666 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.94E-06 | 0 |
| D/N | rs773517655 |
-0.502 | 0.003 | N | 0.052 | 0.08 | 0.229264304666 | gnomAD-4.0.0 | 1.3689E-06 | None | None | None | None | N | None | 2.98846E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99614E-07 | 0 | 0 |
| D/V | None | None | 0.684 | N | 0.407 | 0.302 | 0.458464862945 | gnomAD-4.0.0 | 1.20033E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.31251E-06 | 0 | 0 |
| D/Y | None | None | 0.979 | N | 0.391 | 0.415 | 0.445711490874 | gnomAD-4.0.0 | 6.84451E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52755E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2635 | likely_benign | 0.2166 | benign | -0.409 | Destabilizing | 0.684 | D | 0.317 | neutral | N | 0.478409904 | None | None | N |
| D/C | 0.6518 | likely_pathogenic | 0.6037 | pathogenic | -0.128 | Destabilizing | 0.996 | D | 0.415 | neutral | None | None | None | None | N |
| D/E | 0.1707 | likely_benign | 0.1412 | benign | -0.775 | Destabilizing | 0.007 | N | 0.125 | neutral | N | 0.465244537 | None | None | N |
| D/F | 0.6279 | likely_pathogenic | 0.5915 | pathogenic | -0.456 | Destabilizing | 0.984 | D | 0.389 | neutral | None | None | None | None | N |
| D/G | 0.18 | likely_benign | 0.1632 | benign | -0.703 | Destabilizing | 0.309 | N | 0.327 | neutral | N | 0.468850797 | None | None | N |
| D/H | 0.3782 | ambiguous | 0.3461 | ambiguous | -0.854 | Destabilizing | 0.939 | D | 0.382 | neutral | N | 0.46869944 | None | None | N |
| D/I | 0.5384 | ambiguous | 0.4727 | ambiguous | 0.342 | Stabilizing | 0.91 | D | 0.407 | neutral | None | None | None | None | N |
| D/K | 0.5727 | likely_pathogenic | 0.5121 | ambiguous | -0.301 | Destabilizing | 0.59 | D | 0.354 | neutral | None | None | None | None | N |
| D/L | 0.5352 | ambiguous | 0.4834 | ambiguous | 0.342 | Stabilizing | 0.742 | D | 0.41 | neutral | None | None | None | None | N |
| D/M | 0.6484 | likely_pathogenic | 0.6075 | pathogenic | 0.78 | Stabilizing | 0.996 | D | 0.372 | neutral | None | None | None | None | N |
| D/N | 0.0989 | likely_benign | 0.0933 | benign | -0.557 | Destabilizing | 0.003 | N | 0.052 | neutral | N | 0.477709615 | None | None | N |
| D/P | 0.9159 | likely_pathogenic | 0.888 | pathogenic | 0.117 | Stabilizing | 0.953 | D | 0.411 | neutral | None | None | None | None | N |
| D/Q | 0.4259 | ambiguous | 0.3739 | ambiguous | -0.488 | Destabilizing | 0.835 | D | 0.369 | neutral | None | None | None | None | N |
| D/R | 0.6136 | likely_pathogenic | 0.5685 | pathogenic | -0.292 | Destabilizing | 0.91 | D | 0.376 | neutral | None | None | None | None | N |
| D/S | 0.1563 | likely_benign | 0.136 | benign | -0.783 | Destabilizing | 0.373 | N | 0.284 | neutral | None | None | None | None | N |
| D/T | 0.2453 | likely_benign | 0.2072 | benign | -0.551 | Destabilizing | 0.037 | N | 0.208 | neutral | None | None | None | None | N |
| D/V | 0.3524 | ambiguous | 0.3025 | benign | 0.117 | Stabilizing | 0.684 | D | 0.407 | neutral | N | 0.506313528 | None | None | N |
| D/W | 0.9067 | likely_pathogenic | 0.8969 | pathogenic | -0.419 | Destabilizing | 0.996 | D | 0.536 | neutral | None | None | None | None | N |
| D/Y | 0.2658 | likely_benign | 0.2598 | benign | -0.251 | Destabilizing | 0.979 | D | 0.391 | neutral | N | 0.512643404 | 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.