Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14345 | 43258;43259;43260 | chr2:178633240;178633239;178633238 | chr2:179497967;179497966;179497965 |
| N2AB | 12704 | 38335;38336;38337 | chr2:178633240;178633239;178633238 | chr2:179497967;179497966;179497965 |
| N2A | 11777 | 35554;35555;35556 | chr2:178633240;178633239;178633238 | chr2:179497967;179497966;179497965 |
| N2B | 5280 | 16063;16064;16065 | chr2:178633240;178633239;178633238 | chr2:179497967;179497966;179497965 |
| Novex-1 | 5405 | 16438;16439;16440 | chr2:178633240;178633239;178633238 | chr2:179497967;179497966;179497965 |
| Novex-2 | 5472 | 16639;16640;16641 | chr2:178633240;178633239;178633238 | chr2:179497967;179497966;179497965 |
| 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 | 0.974 | D | 0.46 | 0.354 | 0.435371449458 | gnomAD-4.0.0 | 1.36889E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99682E-07 | 0 | 1.65739E-05 |
| P/R | rs1228136995  |
-0.829 | 0.949 | N | 0.445 | 0.373 | 0.31501682445 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 1.14758E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/R | rs1228136995 |
-0.829 | 0.949 | N | 0.445 | 0.373 | 0.31501682445 | 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 |
| P/R | rs1228136995 |
-0.829 | 0.949 | N | 0.445 | 0.373 | 0.31501682445 | gnomAD-4.0.0 | 1.23984E-06 | None | None | None | None | N | None | 2.67165E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | rs1576701632 |
None | 0.842 | N | 0.381 | 0.262 | 0.223847106136 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | rs1576701632 |
None | 0.842 | N | 0.381 | 0.262 | 0.223847106136 | gnomAD-4.0.0 | 6.57583E-06 | None | None | None | None | N | None | 0 | 6.55652E-05 | 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 | 0.1145 | likely_benign | 0.1164 | benign | -0.799 | Destabilizing | 0.842 | D | 0.369 | neutral | N | 0.460969902 | None | None | N |
| P/C | 0.7845 | likely_pathogenic | 0.7854 | pathogenic | -0.581 | Destabilizing | 0.998 | D | 0.565 | neutral | None | None | None | None | N |
| P/D | 0.4127 | ambiguous | 0.4359 | ambiguous | -0.642 | Destabilizing | 0.009 | N | 0.207 | neutral | None | None | None | None | N |
| P/E | 0.3308 | likely_benign | 0.3485 | ambiguous | -0.748 | Destabilizing | 0.038 | N | 0.211 | neutral | None | None | None | None | N |
| P/F | 0.7777 | likely_pathogenic | 0.7455 | pathogenic | -0.933 | Destabilizing | 0.994 | D | 0.486 | neutral | None | None | None | None | N |
| P/G | 0.4639 | ambiguous | 0.4526 | ambiguous | -0.973 | Destabilizing | 0.876 | D | 0.398 | neutral | None | None | None | None | N |
| P/H | 0.3504 | ambiguous | 0.3517 | ambiguous | -0.557 | Destabilizing | 0.991 | D | 0.413 | neutral | D | 0.528888641 | None | None | N |
| P/I | 0.5785 | likely_pathogenic | 0.5255 | ambiguous | -0.478 | Destabilizing | 0.994 | D | 0.565 | neutral | None | None | None | None | N |
| P/K | 0.4284 | ambiguous | 0.3972 | ambiguous | -0.698 | Destabilizing | 0.876 | D | 0.351 | neutral | None | None | None | None | N |
| P/L | 0.2451 | likely_benign | 0.2205 | benign | -0.478 | Destabilizing | 0.974 | D | 0.46 | neutral | D | 0.528310475 | None | None | N |
| P/M | 0.545 | ambiguous | 0.5093 | ambiguous | -0.343 | Destabilizing | 0.998 | D | 0.43 | neutral | None | None | None | None | N |
| P/N | 0.4462 | ambiguous | 0.4245 | ambiguous | -0.352 | Destabilizing | 0.876 | D | 0.395 | neutral | None | None | None | None | N |
| P/Q | 0.2777 | likely_benign | 0.2718 | benign | -0.632 | Destabilizing | 0.961 | D | 0.42 | neutral | None | None | None | None | N |
| P/R | 0.3131 | likely_benign | 0.2947 | benign | -0.112 | Destabilizing | 0.949 | D | 0.445 | neutral | N | 0.468984074 | None | None | N |
| P/S | 0.1914 | likely_benign | 0.189 | benign | -0.721 | Destabilizing | 0.842 | D | 0.381 | neutral | N | 0.464778725 | None | None | N |
| P/T | 0.1665 | likely_benign | 0.1575 | benign | -0.731 | Destabilizing | 0.915 | D | 0.418 | neutral | N | 0.468158691 | None | None | N |
| P/V | 0.421 | ambiguous | 0.3813 | ambiguous | -0.55 | Destabilizing | 0.981 | D | 0.427 | neutral | None | None | None | None | N |
| P/W | 0.8405 | likely_pathogenic | 0.8416 | pathogenic | -1.017 | Destabilizing | 0.998 | D | 0.594 | neutral | None | None | None | None | N |
| P/Y | 0.6977 | likely_pathogenic | 0.6836 | pathogenic | -0.734 | Destabilizing | 0.994 | D | 0.493 | 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.