Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18458 | 55597;55598;55599 | chr2:178601718;178601717;178601716 | chr2:179466445;179466444;179466443 |
| N2AB | 16817 | 50674;50675;50676 | chr2:178601718;178601717;178601716 | chr2:179466445;179466444;179466443 |
| N2A | 15890 | 47893;47894;47895 | chr2:178601718;178601717;178601716 | chr2:179466445;179466444;179466443 |
| N2B | 9393 | 28402;28403;28404 | chr2:178601718;178601717;178601716 | chr2:179466445;179466444;179466443 |
| Novex-1 | 9518 | 28777;28778;28779 | chr2:178601718;178601717;178601716 | chr2:179466445;179466444;179466443 |
| Novex-2 | 9585 | 28978;28979;28980 | chr2:178601718;178601717;178601716 | chr2:179466445;179466444;179466443 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/G | rs368890202  |
-0.736 | 0.98 | N | 0.517 | 0.152 | None | gnomAD-2.1.1 | 4.07E-06 | None | None | None | None | N | None | 6.49E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/R | rs200550947 |
-0.23 | 0.994 | N | 0.636 | 0.37 | 0.298056030225 | gnomAD-2.1.1 | 4.11537E-04 | None | None | None | None | N | None | 1.65865E-04 | 5.74E-05 | None | 0 | 0 | None | 3.36E-05 | None | 6.44019E-04 | 7.0103E-04 | 2.8401E-04 |
| S/R | rs200550947 |
-0.23 | 0.994 | N | 0.636 | 0.37 | 0.298056030225 | gnomAD-3.1.2 | 6.05096E-04 | None | None | None | None | N | None | 1.92985E-04 | 0 | 0 | 0 | 0 | None | 4.70987E-04 | 0 | 1.16224E-03 | 0 | 0 |
| S/R | rs200550947 |
-0.23 | 0.994 | N | 0.636 | 0.37 | 0.298056030225 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| S/R | rs200550947 |
-0.23 | 0.994 | N | 0.636 | 0.37 | 0.298056030225 | gnomAD-4.0.0 | 6.4023E-04 | None | None | None | None | N | None | 1.4702E-04 | 3.36089E-05 | None | 0 | 0 | None | 7.52045E-04 | 0 | 7.90676E-04 | 1.11037E-05 | 5.93805E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0921 | likely_benign | 0.087 | benign | -0.735 | Destabilizing | 0.931 | D | 0.431 | neutral | None | None | None | None | N |
| S/C | 0.0926 | likely_benign | 0.0931 | benign | -0.583 | Destabilizing | 1.0 | D | 0.661 | neutral | N | 0.48839825 | None | None | N |
| S/D | 0.7843 | likely_pathogenic | 0.7583 | pathogenic | -1.471 | Destabilizing | 0.985 | D | 0.475 | neutral | None | None | None | None | N |
| S/E | 0.7474 | likely_pathogenic | 0.7194 | pathogenic | -1.307 | Destabilizing | 0.985 | D | 0.467 | neutral | None | None | None | None | N |
| S/F | 0.2484 | likely_benign | 0.2198 | benign | -0.75 | Destabilizing | 0.999 | D | 0.729 | prob.delet. | None | None | None | None | N |
| S/G | 0.1731 | likely_benign | 0.1673 | benign | -1.101 | Destabilizing | 0.98 | D | 0.517 | neutral | N | 0.47448759 | None | None | N |
| S/H | 0.3968 | ambiguous | 0.3774 | ambiguous | -1.582 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | N |
| S/I | 0.1617 | likely_benign | 0.1436 | benign | 0.177 | Stabilizing | 0.989 | D | 0.655 | neutral | N | 0.409166675 | None | None | N |
| S/K | 0.7881 | likely_pathogenic | 0.745 | pathogenic | -0.206 | Destabilizing | 0.97 | D | 0.469 | neutral | None | None | None | None | N |
| S/L | 0.1317 | likely_benign | 0.1147 | benign | 0.177 | Stabilizing | 0.97 | D | 0.613 | neutral | None | None | None | None | N |
| S/M | 0.1917 | likely_benign | 0.1637 | benign | 0.161 | Stabilizing | 1.0 | D | 0.666 | neutral | None | None | None | None | N |
| S/N | 0.2439 | likely_benign | 0.2184 | benign | -0.858 | Destabilizing | 0.98 | D | 0.489 | neutral | N | 0.47448759 | None | None | N |
| S/P | 0.9846 | likely_pathogenic | 0.9898 | pathogenic | -0.093 | Destabilizing | 0.999 | D | 0.618 | neutral | None | None | None | None | N |
| S/Q | 0.5519 | ambiguous | 0.5229 | ambiguous | -0.693 | Destabilizing | 0.999 | D | 0.515 | neutral | None | None | None | None | N |
| S/R | 0.6694 | likely_pathogenic | 0.6396 | pathogenic | -0.543 | Destabilizing | 0.994 | D | 0.636 | neutral | N | 0.478679902 | None | None | N |
| S/T | 0.0752 | likely_benign | 0.0714 | benign | -0.52 | Destabilizing | 0.122 | N | 0.229 | neutral | N | 0.375627318 | None | None | N |
| S/V | 0.166 | likely_benign | 0.1478 | benign | -0.093 | Destabilizing | 0.97 | D | 0.619 | neutral | None | None | None | None | N |
| S/W | 0.4353 | ambiguous | 0.4239 | ambiguous | -1.013 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | N |
| S/Y | 0.2417 | likely_benign | 0.2305 | benign | -0.547 | Destabilizing | 0.999 | D | 0.741 | deleterious | 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.