Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23688 | 71287;71288;71289 | chr2:178575070;178575069;178575068 | chr2:179439797;179439796;179439795 |
| N2AB | 22047 | 66364;66365;66366 | chr2:178575070;178575069;178575068 | chr2:179439797;179439796;179439795 |
| N2A | 21120 | 63583;63584;63585 | chr2:178575070;178575069;178575068 | chr2:179439797;179439796;179439795 |
| N2B | 14623 | 44092;44093;44094 | chr2:178575070;178575069;178575068 | chr2:179439797;179439796;179439795 |
| Novex-1 | 14748 | 44467;44468;44469 | chr2:178575070;178575069;178575068 | chr2:179439797;179439796;179439795 |
| Novex-2 | 14815 | 44668;44669;44670 | chr2:178575070;178575069;178575068 | chr2:179439797;179439796;179439795 |
| 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/A | rs935595558  |
None | 0.02 | D | 0.299 | 0.13 | 0.257786959452 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/A | rs935595558 |
None | 0.02 | D | 0.299 | 0.13 | 0.257786959452 | gnomAD-4.0.0 | 2.56368E-06 | None | None | None | None | N | None | 1.69199E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.39402E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0709 | likely_benign | 0.0723 | benign | -0.621 | Destabilizing | 0.02 | N | 0.299 | neutral | D | 0.531750035 | None | None | N |
| S/C | 0.1173 | likely_benign | 0.1176 | benign | -0.695 | Destabilizing | 0.998 | D | 0.691 | prob.neutral | None | None | None | None | N |
| S/D | 0.7078 | likely_pathogenic | 0.6985 | pathogenic | -1.117 | Destabilizing | 0.993 | D | 0.617 | neutral | None | None | None | None | N |
| S/E | 0.6927 | likely_pathogenic | 0.6756 | pathogenic | -1.124 | Destabilizing | 0.953 | D | 0.586 | neutral | None | None | None | None | N |
| S/F | 0.2899 | likely_benign | 0.2803 | benign | -1.029 | Destabilizing | 0.993 | D | 0.737 | prob.delet. | None | None | None | None | N |
| S/G | 0.1338 | likely_benign | 0.1388 | benign | -0.828 | Destabilizing | 0.807 | D | 0.509 | neutral | None | None | None | None | N |
| S/H | 0.4216 | ambiguous | 0.3953 | ambiguous | -1.437 | Destabilizing | 0.999 | D | 0.691 | prob.neutral | None | None | None | None | N |
| S/I | 0.336 | likely_benign | 0.3129 | benign | -0.18 | Destabilizing | 0.986 | D | 0.725 | prob.delet. | None | None | None | None | N |
| S/K | 0.7583 | likely_pathogenic | 0.7329 | pathogenic | -0.752 | Destabilizing | 0.953 | D | 0.585 | neutral | None | None | None | None | N |
| S/L | 0.149 | likely_benign | 0.1428 | benign | -0.18 | Destabilizing | 0.939 | D | 0.627 | neutral | N | 0.430183106 | None | None | N |
| S/M | 0.23 | likely_benign | 0.2238 | benign | 0.177 | Stabilizing | 0.999 | D | 0.693 | prob.neutral | None | None | None | None | N |
| S/N | 0.2537 | likely_benign | 0.2376 | benign | -0.876 | Destabilizing | 0.993 | D | 0.617 | neutral | None | None | None | None | N |
| S/P | 0.9794 | likely_pathogenic | 0.9786 | pathogenic | -0.296 | Destabilizing | 0.991 | D | 0.722 | prob.delet. | D | 0.528115084 | None | None | N |
| S/Q | 0.5658 | likely_pathogenic | 0.5462 | ambiguous | -1.143 | Destabilizing | 0.993 | D | 0.683 | prob.neutral | None | None | None | None | N |
| S/R | 0.6917 | likely_pathogenic | 0.6626 | pathogenic | -0.58 | Destabilizing | 0.993 | D | 0.733 | prob.delet. | None | None | None | None | N |
| S/T | 0.1018 | likely_benign | 0.0959 | benign | -0.774 | Destabilizing | 0.939 | D | 0.51 | neutral | N | 0.48472688 | None | None | N |
| S/V | 0.2406 | likely_benign | 0.2297 | benign | -0.296 | Destabilizing | 0.91 | D | 0.641 | neutral | None | None | None | None | N |
| S/W | 0.5034 | ambiguous | 0.4835 | ambiguous | -1.055 | Destabilizing | 0.999 | D | 0.7 | prob.neutral | None | None | None | None | N |
| S/Y | 0.2422 | likely_benign | 0.229 | benign | -0.73 | Destabilizing | 0.998 | D | 0.726 | prob.delet. | 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.