Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16622 | 50089;50090;50091 | chr2:178612857;178612856;178612855 | chr2:179477584;179477583;179477582 |
| N2AB | 14981 | 45166;45167;45168 | chr2:178612857;178612856;178612855 | chr2:179477584;179477583;179477582 |
| N2A | 14054 | 42385;42386;42387 | chr2:178612857;178612856;178612855 | chr2:179477584;179477583;179477582 |
| N2B | 7557 | 22894;22895;22896 | chr2:178612857;178612856;178612855 | chr2:179477584;179477583;179477582 |
| Novex-1 | 7682 | 23269;23270;23271 | chr2:178612857;178612856;178612855 | chr2:179477584;179477583;179477582 |
| Novex-2 | 7749 | 23470;23471;23472 | chr2:178612857;178612856;178612855 | chr2:179477584;179477583;179477582 |
| 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/P | rs1178148859  |
-0.092 | 0.998 | D | 0.728 | 0.5 | 0.493896554345 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 6.58762E-04 | None | 0 | None | 0 | 0 | 0 |
| S/P | rs1178148859 |
-0.092 | 0.998 | D | 0.728 | 0.5 | 0.493896554345 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.95236E-04 | None | 0 | 0 | 0 | 0 | 0 |
| S/P | rs1178148859 |
-0.092 | 0.998 | D | 0.728 | 0.5 | 0.493896554345 | gnomAD-4.0.0 | 6.58233E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.95236E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1215 | likely_benign | 0.118 | benign | -0.82 | Destabilizing | 0.543 | D | 0.365 | neutral | N | 0.474596311 | None | None | N |
| S/C | 0.1319 | likely_benign | 0.1205 | benign | -0.229 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| S/D | 0.8212 | likely_pathogenic | 0.8498 | pathogenic | -1.39 | Destabilizing | 0.996 | D | 0.652 | neutral | None | None | None | None | N |
| S/E | 0.7454 | likely_pathogenic | 0.7803 | pathogenic | -1.137 | Destabilizing | 0.996 | D | 0.629 | neutral | None | None | None | None | N |
| S/F | 0.3798 | ambiguous | 0.3727 | ambiguous | -0.581 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | N |
| S/G | 0.2362 | likely_benign | 0.2524 | benign | -1.239 | Destabilizing | 0.992 | D | 0.624 | neutral | None | None | None | None | N |
| S/H | 0.5021 | ambiguous | 0.5138 | ambiguous | -1.436 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| S/I | 0.2805 | likely_benign | 0.2798 | benign | 0.279 | Stabilizing | 0.999 | D | 0.734 | prob.delet. | None | None | None | None | N |
| S/K | 0.8773 | likely_pathogenic | 0.8911 | pathogenic | 0.231 | Stabilizing | 0.996 | D | 0.629 | neutral | None | None | None | None | N |
| S/L | 0.1834 | likely_benign | 0.1811 | benign | 0.279 | Stabilizing | 0.989 | D | 0.681 | prob.neutral | N | 0.470770511 | None | None | N |
| S/M | 0.3172 | likely_benign | 0.2919 | benign | 0.016 | Stabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| S/N | 0.3617 | ambiguous | 0.3537 | ambiguous | -0.604 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | N |
| S/P | 0.9891 | likely_pathogenic | 0.9912 | pathogenic | -0.056 | Destabilizing | 0.998 | D | 0.728 | prob.delet. | D | 0.58472277 | None | None | N |
| S/Q | 0.6042 | likely_pathogenic | 0.6149 | pathogenic | -0.222 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| S/R | 0.747 | likely_pathogenic | 0.7951 | pathogenic | -0.361 | Destabilizing | 0.999 | D | 0.733 | prob.delet. | None | None | None | None | N |
| S/T | 0.1221 | likely_benign | 0.119 | benign | -0.216 | Destabilizing | 0.989 | D | 0.626 | neutral | N | 0.465287296 | None | None | N |
| S/V | 0.2714 | likely_benign | 0.2629 | benign | -0.056 | Destabilizing | 0.998 | D | 0.711 | prob.delet. | None | None | None | None | N |
| S/W | 0.5718 | likely_pathogenic | 0.6111 | pathogenic | -0.919 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| S/Y | 0.3173 | likely_benign | 0.325 | benign | -0.411 | Destabilizing | 1.0 | D | 0.781 | deleterious | 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.