Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21234 | 63925;63926;63927 | chr2:178587609;178587608;178587607 | chr2:179452336;179452335;179452334 |
| N2AB | 19593 | 59002;59003;59004 | chr2:178587609;178587608;178587607 | chr2:179452336;179452335;179452334 |
| N2A | 18666 | 56221;56222;56223 | chr2:178587609;178587608;178587607 | chr2:179452336;179452335;179452334 |
| N2B | 12169 | 36730;36731;36732 | chr2:178587609;178587608;178587607 | chr2:179452336;179452335;179452334 |
| Novex-1 | 12294 | 37105;37106;37107 | chr2:178587609;178587608;178587607 | chr2:179452336;179452335;179452334 |
| Novex-2 | 12361 | 37306;37307;37308 | chr2:178587609;178587608;178587607 | chr2:179452336;179452335;179452334 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | None | None | 0.982 | N | 0.659 | 0.482 | 0.58951732002 | gnomAD-4.0.0 | 1.59405E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.79174E-05 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | rs1335943731  |
-1.237 | 0.885 | N | 0.509 | 0.262 | 0.391156786388 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | I | None | 1.14758E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/S | rs1335943731 |
-1.237 | 0.885 | N | 0.509 | 0.262 | 0.391156786388 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | rs1335943731 |
-1.237 | 0.885 | N | 0.509 | 0.262 | 0.391156786388 | gnomAD-4.0.0 | 3.04544E-06 | None | None | None | None | I | None | 5.24512E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.1511 | likely_benign | 0.1856 | benign | -0.819 | Destabilizing | 0.046 | N | 0.31 | neutral | N | 0.500560337 | None | None | I |
| P/C | 0.784 | likely_pathogenic | 0.8273 | pathogenic | -0.773 | Destabilizing | 0.999 | D | 0.697 | prob.neutral | None | None | None | None | I |
| P/D | 0.6654 | likely_pathogenic | 0.6903 | pathogenic | -0.457 | Destabilizing | 0.993 | D | 0.587 | neutral | None | None | None | None | I |
| P/E | 0.4308 | ambiguous | 0.455 | ambiguous | -0.542 | Destabilizing | 0.986 | D | 0.585 | neutral | None | None | None | None | I |
| P/F | 0.864 | likely_pathogenic | 0.8983 | pathogenic | -0.824 | Destabilizing | 0.999 | D | 0.707 | prob.neutral | None | None | None | None | I |
| P/G | 0.4213 | ambiguous | 0.483 | ambiguous | -1.019 | Destabilizing | 0.91 | D | 0.554 | neutral | None | None | None | None | I |
| P/H | 0.4099 | ambiguous | 0.4519 | ambiguous | -0.498 | Destabilizing | 0.999 | D | 0.648 | neutral | D | 0.53365419 | None | None | I |
| P/I | 0.7022 | likely_pathogenic | 0.7609 | pathogenic | -0.423 | Destabilizing | 0.986 | D | 0.727 | prob.delet. | None | None | None | None | I |
| P/K | 0.5817 | likely_pathogenic | 0.6251 | pathogenic | -0.678 | Destabilizing | 0.986 | D | 0.587 | neutral | None | None | None | None | I |
| P/L | 0.316 | likely_benign | 0.3531 | ambiguous | -0.423 | Destabilizing | 0.982 | D | 0.659 | neutral | N | 0.518319378 | None | None | I |
| P/M | 0.607 | likely_pathogenic | 0.6623 | pathogenic | -0.371 | Destabilizing | 0.999 | D | 0.646 | neutral | None | None | None | None | I |
| P/N | 0.4923 | ambiguous | 0.5393 | ambiguous | -0.42 | Destabilizing | 0.993 | D | 0.671 | neutral | None | None | None | None | I |
| P/Q | 0.2836 | likely_benign | 0.3136 | benign | -0.667 | Destabilizing | 0.993 | D | 0.649 | neutral | None | None | None | None | I |
| P/R | 0.43 | ambiguous | 0.4598 | ambiguous | -0.119 | Destabilizing | 0.991 | D | 0.676 | prob.neutral | N | 0.478299553 | None | None | I |
| P/S | 0.211 | likely_benign | 0.2477 | benign | -0.88 | Destabilizing | 0.885 | D | 0.509 | neutral | N | 0.479414273 | None | None | I |
| P/T | 0.208 | likely_benign | 0.2309 | benign | -0.859 | Destabilizing | 0.322 | N | 0.285 | neutral | N | 0.511777408 | None | None | I |
| P/V | 0.5108 | ambiguous | 0.5658 | pathogenic | -0.518 | Destabilizing | 0.91 | D | 0.569 | neutral | None | None | None | None | I |
| P/W | 0.8929 | likely_pathogenic | 0.9032 | pathogenic | -0.894 | Destabilizing | 0.999 | D | 0.685 | prob.neutral | None | None | None | None | I |
| P/Y | 0.7835 | likely_pathogenic | 0.8203 | pathogenic | -0.607 | Destabilizing | 0.999 | D | 0.711 | 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.