Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25415 | 76468;76469;76470 | chr2:178569889;178569888;178569887 | chr2:179434616;179434615;179434614 |
| N2AB | 23774 | 71545;71546;71547 | chr2:178569889;178569888;178569887 | chr2:179434616;179434615;179434614 |
| N2A | 22847 | 68764;68765;68766 | chr2:178569889;178569888;178569887 | chr2:179434616;179434615;179434614 |
| N2B | 16350 | 49273;49274;49275 | chr2:178569889;178569888;178569887 | chr2:179434616;179434615;179434614 |
| Novex-1 | 16475 | 49648;49649;49650 | chr2:178569889;178569888;178569887 | chr2:179434616;179434615;179434614 |
| Novex-2 | 16542 | 49849;49850;49851 | chr2:178569889;178569888;178569887 | chr2:179434616;179434615;179434614 |
| 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/R | rs748670245  |
0.043 | 0.055 | N | 0.45 | 0.105 | 0.26547132957 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| I/R | rs748670245 |
0.043 | 0.055 | N | 0.45 | 0.105 | 0.26547132957 | gnomAD-4.0.0 | 8.89644E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.16945E-05 | 0 | 0 |
| I/T | rs748670245 |
-0.954 | None | N | 0.121 | 0.105 | 0.173771789658 | gnomAD-4.0.0 | 2.73737E-06 | None | None | None | None | N | None | 0 | 0 | None | 3.82966E-05 | 0 | None | 0 | 0 | 8.99573E-07 | 1.15955E-05 | 1.65711E-05 |
| I/V | rs1707513771 |
None | None | N | 0.053 | 0.148 | 0.225215365344 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.75482E-04 | 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 | 0.0928 | likely_benign | 0.0961 | benign | -1.083 | Destabilizing | None | N | 0.125 | neutral | None | None | None | None | N |
| I/C | 0.382 | ambiguous | 0.3982 | ambiguous | -0.772 | Destabilizing | 0.356 | N | 0.311 | neutral | None | None | None | None | N |
| I/D | 0.359 | ambiguous | 0.349 | ambiguous | -0.258 | Destabilizing | 0.072 | N | 0.474 | neutral | None | None | None | None | N |
| I/E | 0.2527 | likely_benign | 0.2405 | benign | -0.275 | Destabilizing | 0.072 | N | 0.422 | neutral | None | None | None | None | N |
| I/F | 0.1084 | likely_benign | 0.1097 | benign | -0.664 | Destabilizing | 0.072 | N | 0.247 | neutral | None | None | None | None | N |
| I/G | 0.2685 | likely_benign | 0.2642 | benign | -1.348 | Destabilizing | 0.016 | N | 0.371 | neutral | None | None | None | None | N |
| I/H | 0.2371 | likely_benign | 0.2452 | benign | -0.393 | Destabilizing | 0.628 | D | 0.339 | neutral | None | None | None | None | N |
| I/K | 0.1366 | likely_benign | 0.1352 | benign | -0.652 | Destabilizing | 0.055 | N | 0.383 | neutral | N | 0.409292466 | None | None | N |
| I/L | 0.0768 | likely_benign | 0.0771 | benign | -0.459 | Destabilizing | None | N | 0.055 | neutral | N | 0.37217966 | None | None | N |
| I/M | 0.0582 | likely_benign | 0.0586 | benign | -0.486 | Destabilizing | 0.001 | N | 0.19 | neutral | N | 0.44846693 | None | None | N |
| I/N | 0.1112 | likely_benign | 0.1226 | benign | -0.574 | Destabilizing | 0.072 | N | 0.449 | neutral | None | None | None | None | N |
| I/P | 0.6022 | likely_pathogenic | 0.5327 | ambiguous | -0.634 | Destabilizing | 0.136 | N | 0.454 | neutral | None | None | None | None | N |
| I/Q | 0.1654 | likely_benign | 0.1676 | benign | -0.72 | Destabilizing | 0.214 | N | 0.459 | neutral | None | None | None | None | N |
| I/R | 0.1126 | likely_benign | 0.1034 | benign | -0.086 | Destabilizing | 0.055 | N | 0.45 | neutral | N | 0.437460503 | None | None | N |
| I/S | 0.0936 | likely_benign | 0.1016 | benign | -1.165 | Destabilizing | 0.016 | N | 0.291 | neutral | None | None | None | None | N |
| I/T | 0.0495 | likely_benign | 0.0516 | benign | -1.065 | Destabilizing | None | N | 0.121 | neutral | N | 0.333831916 | None | None | N |
| I/V | 0.0579 | likely_benign | 0.0583 | benign | -0.634 | Destabilizing | None | N | 0.053 | neutral | N | 0.357460924 | None | None | N |
| I/W | 0.5281 | ambiguous | 0.481 | ambiguous | -0.699 | Destabilizing | 0.864 | D | 0.338 | neutral | None | None | None | None | N |
| I/Y | 0.3178 | likely_benign | 0.3203 | benign | -0.469 | Destabilizing | 0.356 | N | 0.435 | 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.