Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26453 | 79582;79583;79584 | chr2:178566775;178566774;178566773 | chr2:179431502;179431501;179431500 |
| N2AB | 24812 | 74659;74660;74661 | chr2:178566775;178566774;178566773 | chr2:179431502;179431501;179431500 |
| N2A | 23885 | 71878;71879;71880 | chr2:178566775;178566774;178566773 | chr2:179431502;179431501;179431500 |
| N2B | 17388 | 52387;52388;52389 | chr2:178566775;178566774;178566773 | chr2:179431502;179431501;179431500 |
| Novex-1 | 17513 | 52762;52763;52764 | chr2:178566775;178566774;178566773 | chr2:179431502;179431501;179431500 |
| Novex-2 | 17580 | 52963;52964;52965 | chr2:178566775;178566774;178566773 | chr2:179431502;179431501;179431500 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/D | rs1299909025  |
-0.516 | 0.999 | N | 0.552 | 0.316 | 0.301455362545 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.58E-05 | None | 0 | None | 0 | 0 | 0 |
| E/D | rs1299909025 |
-0.516 | 0.999 | N | 0.552 | 0.316 | 0.301455362545 | gnomAD-4.0.0 | 1.59214E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77608E-05 | None | 0 | 0 | 0 | 0 | 0 |
| E/K | None | None | 0.999 | N | 0.666 | 0.385 | 0.483224754729 | gnomAD-4.0.0 | 1.59227E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85889E-06 | 0 | 0 |
| E/V | None | None | 1.0 | N | 0.669 | 0.513 | 0.652849316004 | gnomAD-4.0.0 | 1.59213E-06 | None | None | None | None | N | None | 5.65867E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.2204 | likely_benign | 0.1708 | benign | -0.427 | Destabilizing | 0.999 | D | 0.663 | neutral | N | 0.475354803 | None | None | N |
| E/C | 0.9214 | likely_pathogenic | 0.8852 | pathogenic | 0.011 | Stabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| E/D | 0.3389 | likely_benign | 0.2734 | benign | -0.83 | Destabilizing | 0.999 | D | 0.552 | neutral | N | 0.497666248 | None | None | N |
| E/F | 0.9417 | likely_pathogenic | 0.8996 | pathogenic | -0.612 | Destabilizing | 1.0 | D | 0.696 | prob.neutral | None | None | None | None | N |
| E/G | 0.3501 | ambiguous | 0.274 | benign | -0.671 | Destabilizing | 1.0 | D | 0.662 | neutral | N | 0.507136449 | None | None | N |
| E/H | 0.8014 | likely_pathogenic | 0.7312 | pathogenic | -0.849 | Destabilizing | 1.0 | D | 0.663 | neutral | None | None | None | None | N |
| E/I | 0.6347 | likely_pathogenic | 0.522 | ambiguous | 0.193 | Stabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| E/K | 0.3112 | likely_benign | 0.2497 | benign | -0.123 | Destabilizing | 0.999 | D | 0.666 | neutral | N | 0.492537686 | None | None | N |
| E/L | 0.7276 | likely_pathogenic | 0.6357 | pathogenic | 0.193 | Stabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| E/M | 0.7016 | likely_pathogenic | 0.6157 | pathogenic | 0.579 | Stabilizing | 1.0 | D | 0.653 | neutral | None | None | None | None | N |
| E/N | 0.5445 | ambiguous | 0.4621 | ambiguous | -0.285 | Destabilizing | 1.0 | D | 0.706 | prob.neutral | None | None | None | None | N |
| E/P | 0.5251 | ambiguous | 0.4609 | ambiguous | 0.008 | Stabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | N |
| E/Q | 0.2462 | likely_benign | 0.2061 | benign | -0.264 | Destabilizing | 1.0 | D | 0.666 | neutral | N | 0.490157829 | None | None | N |
| E/R | 0.4903 | ambiguous | 0.4007 | ambiguous | -0.075 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| E/S | 0.3819 | ambiguous | 0.2988 | benign | -0.495 | Destabilizing | 0.999 | D | 0.684 | prob.neutral | None | None | None | None | N |
| E/T | 0.4231 | ambiguous | 0.3387 | benign | -0.313 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| E/V | 0.3992 | ambiguous | 0.3157 | benign | 0.008 | Stabilizing | 1.0 | D | 0.669 | neutral | N | 0.497666248 | None | None | N |
| E/W | 0.983 | likely_pathogenic | 0.97 | pathogenic | -0.602 | Destabilizing | 1.0 | D | 0.704 | prob.neutral | None | None | None | None | N |
| E/Y | 0.9203 | likely_pathogenic | 0.864 | pathogenic | -0.412 | Destabilizing | 1.0 | D | 0.678 | prob.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.