Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30725 | 92398;92399;92400 | chr2:178549453;178549452;178549451 | chr2:179414180;179414179;179414178 |
| N2AB | 29084 | 87475;87476;87477 | chr2:178549453;178549452;178549451 | chr2:179414180;179414179;179414178 |
| N2A | 28157 | 84694;84695;84696 | chr2:178549453;178549452;178549451 | chr2:179414180;179414179;179414178 |
| N2B | 21660 | 65203;65204;65205 | chr2:178549453;178549452;178549451 | chr2:179414180;179414179;179414178 |
| Novex-1 | 21785 | 65578;65579;65580 | chr2:178549453;178549452;178549451 | chr2:179414180;179414179;179414178 |
| Novex-2 | 21852 | 65779;65780;65781 | chr2:178549453;178549452;178549451 | chr2:179414180;179414179;179414178 |
| 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 | 0.171 | N | 0.496 | 0.029 | 0.350746614512 | 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 |
| I/V | rs1279357858  |
-0.255 | None | N | 0.151 | 0.1 | 0.438806408302 | gnomAD-2.1.1 | 7.24E-06 | None | None | None | None | I | None | 0 | 5.75E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs1279357858 |
-0.255 | None | N | 0.151 | 0.1 | 0.438806408302 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.78011E-04 |
| I/V | rs1279357858 |
-0.255 | None | N | 0.151 | 0.1 | 0.438806408302 | gnomAD-4.0.0 | 5.17689E-06 | None | None | None | None | I | None | 0 | 3.42442E-05 | None | 0 | 0 | None | 0 | 0 | 2.42428E-06 | 0 | 2.87969E-05 |
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 | 0.1277 | likely_benign | 0.1753 | benign | -1.132 | Destabilizing | 0.007 | N | 0.268 | neutral | None | None | None | None | I |
| I/C | 0.3241 | likely_benign | 0.4037 | ambiguous | -0.751 | Destabilizing | 0.356 | N | 0.492 | neutral | None | None | None | None | I |
| I/D | 0.3707 | ambiguous | 0.4506 | ambiguous | -0.415 | Destabilizing | 0.072 | N | 0.461 | neutral | None | None | None | None | I |
| I/E | 0.2812 | likely_benign | 0.3284 | benign | -0.49 | Destabilizing | 0.072 | N | 0.458 | neutral | None | None | None | None | I |
| I/F | 0.1162 | likely_benign | 0.1448 | benign | -1.073 | Destabilizing | 0.055 | N | 0.489 | neutral | N | 0.511150185 | None | None | I |
| I/G | 0.3712 | ambiguous | 0.5061 | ambiguous | -1.34 | Destabilizing | 0.072 | N | 0.405 | neutral | None | None | None | None | I |
| I/H | 0.2581 | likely_benign | 0.3134 | benign | -0.599 | Destabilizing | 0.628 | D | 0.426 | neutral | None | None | None | None | I |
| I/K | 0.1646 | likely_benign | 0.182 | benign | -0.512 | Destabilizing | 0.072 | N | 0.456 | neutral | None | None | None | None | I |
| I/L | 0.0796 | likely_benign | 0.0897 | benign | -0.686 | Destabilizing | 0.005 | N | 0.209 | neutral | N | 0.457931775 | None | None | I |
| I/M | 0.079 | likely_benign | 0.0886 | benign | -0.497 | Destabilizing | 0.171 | N | 0.496 | neutral | N | 0.467956768 | None | None | I |
| I/N | 0.1091 | likely_benign | 0.1249 | benign | -0.267 | Destabilizing | 0.055 | N | 0.513 | neutral | N | 0.387122109 | None | None | I |
| I/P | 0.2087 | likely_benign | 0.286 | benign | -0.802 | Destabilizing | 0.136 | N | 0.518 | neutral | None | None | None | None | I |
| I/Q | 0.1928 | likely_benign | 0.2261 | benign | -0.548 | Destabilizing | 0.356 | N | 0.507 | neutral | None | None | None | None | I |
| I/R | 0.1393 | likely_benign | 0.1644 | benign | 0.067 | Stabilizing | 0.214 | N | 0.53 | neutral | None | None | None | None | I |
| I/S | 0.1164 | likely_benign | 0.1458 | benign | -0.823 | Destabilizing | 0.012 | N | 0.388 | neutral | N | 0.37964435 | None | None | I |
| I/T | 0.0684 | likely_benign | 0.0924 | benign | -0.79 | Destabilizing | None | N | 0.207 | neutral | N | 0.348572082 | None | None | I |
| I/V | 0.0679 | likely_benign | 0.0738 | benign | -0.802 | Destabilizing | None | N | 0.151 | neutral | N | 0.431689323 | None | None | I |
| I/W | 0.5786 | likely_pathogenic | 0.7048 | pathogenic | -1.037 | Destabilizing | 0.864 | D | 0.438 | neutral | None | None | None | None | I |
| I/Y | 0.2646 | likely_benign | 0.303 | benign | -0.782 | Destabilizing | 0.356 | N | 0.567 | neutral | 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.