Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29822 | 89689;89690;89691 | chr2:178553541;178553540;178553539 | chr2:179418268;179418267;179418266 |
| N2AB | 28181 | 84766;84767;84768 | chr2:178553541;178553540;178553539 | chr2:179418268;179418267;179418266 |
| N2A | 27254 | 81985;81986;81987 | chr2:178553541;178553540;178553539 | chr2:179418268;179418267;179418266 |
| N2B | 20757 | 62494;62495;62496 | chr2:178553541;178553540;178553539 | chr2:179418268;179418267;179418266 |
| Novex-1 | 20882 | 62869;62870;62871 | chr2:178553541;178553540;178553539 | chr2:179418268;179418267;179418266 |
| Novex-2 | 20949 | 63070;63071;63072 | chr2:178553541;178553540;178553539 | chr2:179418268;179418267;179418266 |
| 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/M | rs754018369  |
-0.885 | 0.075 | N | 0.421 | 0.071 | 0.245660935333 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.28E-05 | None | 0 | 0 | 0 |
| I/M | rs754018369 |
-0.885 | 0.075 | N | 0.421 | 0.071 | 0.245660935333 | gnomAD-4.0.0 | 1.59175E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43357E-05 | 0 |
| I/T | None | None | 0.722 | N | 0.599 | 0.218 | 0.504297271243 | gnomAD-4.0.0 | 2.73721E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.7991E-06 | 2.31949E-05 | 0 |
| I/V | None | None | 0.19 | N | 0.416 | 0.096 | 0.332133492242 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.1154 | likely_benign | 0.1173 | benign | -2.224 | Highly Destabilizing | 0.044 | N | 0.351 | neutral | None | None | None | None | I |
| I/C | 0.5963 | likely_pathogenic | 0.605 | pathogenic | -1.354 | Destabilizing | 0.996 | D | 0.719 | prob.delet. | None | None | None | None | I |
| I/D | 0.6774 | likely_pathogenic | 0.6689 | pathogenic | -2.171 | Highly Destabilizing | 0.961 | D | 0.749 | deleterious | None | None | None | None | I |
| I/E | 0.4863 | ambiguous | 0.4744 | ambiguous | -2.053 | Highly Destabilizing | 0.961 | D | 0.731 | prob.delet. | None | None | None | None | I |
| I/F | 0.2701 | likely_benign | 0.2455 | benign | -1.348 | Destabilizing | 0.923 | D | 0.607 | neutral | None | None | None | None | I |
| I/G | 0.494 | ambiguous | 0.4969 | ambiguous | -2.664 | Highly Destabilizing | 0.775 | D | 0.693 | prob.neutral | None | None | None | None | I |
| I/H | 0.6311 | likely_pathogenic | 0.6044 | pathogenic | -2.013 | Highly Destabilizing | 0.996 | D | 0.773 | deleterious | None | None | None | None | I |
| I/K | 0.4301 | ambiguous | 0.3912 | ambiguous | -1.746 | Destabilizing | 0.901 | D | 0.72 | prob.delet. | N | 0.4722963 | None | None | I |
| I/L | 0.1237 | likely_benign | 0.1132 | benign | -1.008 | Destabilizing | 0.075 | N | 0.416 | neutral | N | 0.445955061 | None | None | I |
| I/M | 0.0869 | likely_benign | 0.088 | benign | -0.81 | Destabilizing | 0.075 | N | 0.421 | neutral | N | 0.490882061 | None | None | I |
| I/N | 0.3586 | ambiguous | 0.3405 | ambiguous | -1.76 | Destabilizing | 0.961 | D | 0.764 | deleterious | None | None | None | None | I |
| I/P | 0.8605 | likely_pathogenic | 0.8418 | pathogenic | -1.389 | Destabilizing | 0.961 | D | 0.756 | deleterious | None | None | None | None | I |
| I/Q | 0.4238 | ambiguous | 0.4129 | ambiguous | -1.794 | Destabilizing | 0.961 | D | 0.765 | deleterious | None | None | None | None | I |
| I/R | 0.345 | ambiguous | 0.3012 | benign | -1.253 | Destabilizing | 0.901 | D | 0.757 | deleterious | N | 0.453614539 | None | None | I |
| I/S | 0.1939 | likely_benign | 0.1938 | benign | -2.402 | Highly Destabilizing | 0.633 | D | 0.634 | neutral | None | None | None | None | I |
| I/T | 0.0883 | likely_benign | 0.0846 | benign | -2.167 | Highly Destabilizing | 0.722 | D | 0.599 | neutral | N | 0.434335345 | None | None | I |
| I/V | 0.066 | likely_benign | 0.0629 | benign | -1.389 | Destabilizing | 0.19 | N | 0.416 | neutral | N | 0.417517666 | None | None | I |
| I/W | 0.8558 | likely_pathogenic | 0.835 | pathogenic | -1.632 | Destabilizing | 0.996 | D | 0.777 | deleterious | None | None | None | None | I |
| I/Y | 0.6564 | likely_pathogenic | 0.6318 | pathogenic | -1.377 | Destabilizing | 0.961 | D | 0.725 | prob.delet. | 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.