Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14989 | 45190;45191;45192 | chr2:178621957;178621956;178621955 | chr2:179486684;179486683;179486682 |
| N2AB | 13348 | 40267;40268;40269 | chr2:178621957;178621956;178621955 | chr2:179486684;179486683;179486682 |
| N2A | 12421 | 37486;37487;37488 | chr2:178621957;178621956;178621955 | chr2:179486684;179486683;179486682 |
| N2B | 5924 | 17995;17996;17997 | chr2:178621957;178621956;178621955 | chr2:179486684;179486683;179486682 |
| Novex-1 | 6049 | 18370;18371;18372 | chr2:178621957;178621956;178621955 | chr2:179486684;179486683;179486682 |
| Novex-2 | 6116 | 18571;18572;18573 | chr2:178621957;178621956;178621955 | chr2:179486684;179486683;179486682 |
| 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 | None | None | 0.489 | N | 0.281 | 0.201 | 0.492064528124 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| I/V | rs755040094  |
-1.058 | 0.689 | N | 0.34 | 0.213 | None | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | N | None | 6.51E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs755040094 |
-1.058 | 0.689 | N | 0.34 | 0.213 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs755040094 |
-1.058 | 0.689 | N | 0.34 | 0.213 | None | gnomAD-4.0.0 | 5.14011E-06 | None | None | None | None | N | None | 6.77943E-05 | 0 | None | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.7288 | likely_pathogenic | 0.7826 | pathogenic | -2.094 | Highly Destabilizing | 0.97 | D | 0.523 | neutral | None | None | None | None | N |
| I/C | 0.9002 | likely_pathogenic | 0.9144 | pathogenic | -1.309 | Destabilizing | 1.0 | D | 0.586 | neutral | None | None | None | None | N |
| I/D | 0.9118 | likely_pathogenic | 0.9458 | pathogenic | -1.888 | Destabilizing | 0.999 | D | 0.703 | prob.neutral | None | None | None | None | N |
| I/E | 0.8395 | likely_pathogenic | 0.8962 | pathogenic | -1.73 | Destabilizing | 0.999 | D | 0.69 | prob.neutral | None | None | None | None | N |
| I/F | 0.2852 | likely_benign | 0.3077 | benign | -1.222 | Destabilizing | 0.989 | D | 0.513 | neutral | N | 0.509996316 | None | None | N |
| I/G | 0.9254 | likely_pathogenic | 0.9458 | pathogenic | -2.577 | Highly Destabilizing | 0.996 | D | 0.693 | prob.neutral | None | None | None | None | N |
| I/H | 0.8391 | likely_pathogenic | 0.8871 | pathogenic | -1.866 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| I/K | 0.8063 | likely_pathogenic | 0.8628 | pathogenic | -1.548 | Destabilizing | 0.996 | D | 0.692 | prob.neutral | None | None | None | None | N |
| I/L | 0.2222 | likely_benign | 0.2383 | benign | -0.749 | Destabilizing | 0.689 | D | 0.259 | neutral | N | 0.50893731 | None | None | N |
| I/M | 0.154 | likely_benign | 0.1578 | benign | -0.614 | Destabilizing | 0.489 | N | 0.281 | neutral | N | 0.500954649 | None | None | N |
| I/N | 0.5995 | likely_pathogenic | 0.6969 | pathogenic | -1.694 | Destabilizing | 0.998 | D | 0.703 | prob.neutral | D | 0.734402725 | None | None | N |
| I/P | 0.9648 | likely_pathogenic | 0.9736 | pathogenic | -1.172 | Destabilizing | 0.999 | D | 0.7 | prob.neutral | None | None | None | None | N |
| I/Q | 0.7792 | likely_pathogenic | 0.8484 | pathogenic | -1.654 | Destabilizing | 0.996 | D | 0.704 | prob.neutral | None | None | None | None | N |
| I/R | 0.7248 | likely_pathogenic | 0.7918 | pathogenic | -1.161 | Destabilizing | 0.996 | D | 0.701 | prob.neutral | None | None | None | None | N |
| I/S | 0.6449 | likely_pathogenic | 0.7167 | pathogenic | -2.404 | Highly Destabilizing | 0.994 | D | 0.587 | neutral | D | 0.644347191 | None | None | N |
| I/T | 0.526 | ambiguous | 0.5914 | pathogenic | -2.106 | Highly Destabilizing | 0.98 | D | 0.535 | neutral | D | 0.582079553 | None | None | N |
| I/V | 0.1319 | likely_benign | 0.1426 | benign | -1.172 | Destabilizing | 0.689 | D | 0.34 | neutral | N | 0.494011188 | None | None | N |
| I/W | 0.9046 | likely_pathogenic | 0.9227 | pathogenic | -1.508 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| I/Y | 0.7097 | likely_pathogenic | 0.7645 | pathogenic | -1.204 | Destabilizing | 0.999 | D | 0.592 | 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.