Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29856 | 89791;89792;89793 | chr2:178553334;178553333;178553332 | chr2:179418061;179418060;179418059 |
| N2AB | 28215 | 84868;84869;84870 | chr2:178553334;178553333;178553332 | chr2:179418061;179418060;179418059 |
| N2A | 27288 | 82087;82088;82089 | chr2:178553334;178553333;178553332 | chr2:179418061;179418060;179418059 |
| N2B | 20791 | 62596;62597;62598 | chr2:178553334;178553333;178553332 | chr2:179418061;179418060;179418059 |
| Novex-1 | 20916 | 62971;62972;62973 | chr2:178553334;178553333;178553332 | chr2:179418061;179418060;179418059 |
| Novex-2 | 20983 | 63172;63173;63174 | chr2:178553334;178553333;178553332 | chr2:179418061;179418060;179418059 |
| 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/E | None | None | 0.989 | N | 0.451 | 0.151 | 0.262175524916 | gnomAD-4.0.0 | 6.88879E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00946E-07 | 0 | 0 |
| D/Y | rs1244755099  |
-0.021 | 1.0 | N | 0.617 | 0.289 | 0.435590266561 | gnomAD-2.1.1 | 4.13E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.29E-05 | None | 0 | 0 | 0 |
| D/Y | rs1244755099 |
-0.021 | 1.0 | N | 0.617 | 0.289 | 0.435590266561 | gnomAD-4.0.0 | 1.61856E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43575E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1714 | likely_benign | 0.1678 | benign | -0.407 | Destabilizing | 0.989 | D | 0.481 | neutral | N | 0.429504662 | None | None | I |
| D/C | 0.6514 | likely_pathogenic | 0.6459 | pathogenic | -0.185 | Destabilizing | 1.0 | D | 0.653 | neutral | None | None | None | None | I |
| D/E | 0.2275 | likely_benign | 0.2287 | benign | -0.681 | Destabilizing | 0.989 | D | 0.451 | neutral | N | 0.446415555 | None | None | I |
| D/F | 0.6088 | likely_pathogenic | 0.595 | pathogenic | -0.265 | Destabilizing | 1.0 | D | 0.627 | neutral | None | None | None | None | I |
| D/G | 0.2286 | likely_benign | 0.2247 | benign | -0.714 | Destabilizing | 0.989 | D | 0.483 | neutral | N | 0.489206327 | None | None | I |
| D/H | 0.2743 | likely_benign | 0.2807 | benign | -0.611 | Destabilizing | 1.0 | D | 0.542 | neutral | N | 0.471140641 | None | None | I |
| D/I | 0.3431 | ambiguous | 0.3346 | benign | 0.385 | Stabilizing | 0.998 | D | 0.637 | neutral | None | None | None | None | I |
| D/K | 0.3801 | ambiguous | 0.4032 | ambiguous | -0.397 | Destabilizing | 0.998 | D | 0.519 | neutral | None | None | None | None | I |
| D/L | 0.4059 | ambiguous | 0.409 | ambiguous | 0.385 | Stabilizing | 0.998 | D | 0.627 | neutral | None | None | None | None | I |
| D/M | 0.5679 | likely_pathogenic | 0.5709 | pathogenic | 0.725 | Stabilizing | 1.0 | D | 0.621 | neutral | None | None | None | None | I |
| D/N | 0.1011 | likely_benign | 0.0993 | benign | -0.693 | Destabilizing | 0.733 | D | 0.268 | neutral | N | 0.428464512 | None | None | I |
| D/P | 0.5614 | ambiguous | 0.5531 | ambiguous | 0.146 | Stabilizing | 1.0 | D | 0.567 | neutral | None | None | None | None | I |
| D/Q | 0.3721 | ambiguous | 0.3872 | ambiguous | -0.579 | Destabilizing | 0.999 | D | 0.539 | neutral | None | None | None | None | I |
| D/R | 0.4521 | ambiguous | 0.4788 | ambiguous | -0.284 | Destabilizing | 0.999 | D | 0.58 | neutral | None | None | None | None | I |
| D/S | 0.1476 | likely_benign | 0.1471 | benign | -0.889 | Destabilizing | 0.983 | D | 0.443 | neutral | None | None | None | None | I |
| D/T | 0.194 | likely_benign | 0.1961 | benign | -0.652 | Destabilizing | 0.784 | D | 0.303 | neutral | None | None | None | None | I |
| D/V | 0.2033 | likely_benign | 0.2002 | benign | 0.146 | Stabilizing | 0.997 | D | 0.624 | neutral | N | 0.451765446 | None | None | I |
| D/W | 0.8988 | likely_pathogenic | 0.8958 | pathogenic | -0.189 | Destabilizing | 1.0 | D | 0.67 | neutral | None | None | None | None | I |
| D/Y | 0.2313 | likely_benign | 0.2225 | benign | -0.071 | Destabilizing | 1.0 | D | 0.617 | neutral | N | 0.504810497 | 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.