Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35694 | 107305;107306;107307 | chr2:178528671;178528670;178528669 | chr2:179393398;179393397;179393396 |
| N2AB | 34053 | 102382;102383;102384 | chr2:178528671;178528670;178528669 | chr2:179393398;179393397;179393396 |
| N2A | 33126 | 99601;99602;99603 | chr2:178528671;178528670;178528669 | chr2:179393398;179393397;179393396 |
| N2B | 26629 | 80110;80111;80112 | chr2:178528671;178528670;178528669 | chr2:179393398;179393397;179393396 |
| Novex-1 | 26754 | 80485;80486;80487 | chr2:178528671;178528670;178528669 | chr2:179393398;179393397;179393396 |
| Novex-2 | 26821 | 80686;80687;80688 | chr2:178528671;178528670;178528669 | chr2:179393398;179393397;179393396 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/P | rs761325938  |
-1.633 | 0.966 | N | 0.421 | 0.493 | 0.725424417769 | gnomAD-2.1.1 | 8.08E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.57E-05 | None | 0 | 0 | 0 |
| L/P | rs761325938 |
-1.633 | 0.966 | N | 0.421 | 0.493 | 0.725424417769 | gnomAD-4.0.0 | 6.36961E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 5.74168E-05 | 0 |
| L/V | rs769369764 |
-1.366 | 0.002 | N | 0.089 | 0.026 | 0.104622674875 | gnomAD-2.1.1 | 7.89E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 9.77769E-04 | None | 0 | None | 0 | 7.84E-06 | 2.81849E-04 |
| L/V | rs769369764 |
-1.366 | 0.002 | N | 0.089 | 0.026 | 0.104622674875 | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | N | None | 2.41E-05 | 6.55E-05 | 0 | 0 | 9.62649E-04 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| L/V | rs769369764 |
-1.366 | 0.002 | N | 0.089 | 0.026 | 0.104622674875 | gnomAD-4.0.0 | 4.40085E-05 | None | None | None | None | N | None | 1.3328E-05 | 1.66895E-05 | None | 0 | 1.2038E-03 | None | 0 | 0 | 1.10207E-05 | 1.09955E-05 | 1.60082E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.3843 | ambiguous | 0.5289 | ambiguous | -1.436 | Destabilizing | 0.029 | N | 0.129 | neutral | None | None | None | None | N |
| L/C | 0.6799 | likely_pathogenic | 0.8096 | pathogenic | -1.055 | Destabilizing | 0.991 | D | 0.337 | neutral | None | None | None | None | N |
| L/D | 0.8589 | likely_pathogenic | 0.9339 | pathogenic | -1.205 | Destabilizing | 0.974 | D | 0.414 | neutral | None | None | None | None | N |
| L/E | 0.6168 | likely_pathogenic | 0.7654 | pathogenic | -1.25 | Destabilizing | 0.915 | D | 0.411 | neutral | None | None | None | None | N |
| L/F | 0.1801 | likely_benign | 0.2321 | benign | -1.367 | Destabilizing | 0.016 | N | 0.16 | neutral | None | None | None | None | N |
| L/G | 0.6999 | likely_pathogenic | 0.8167 | pathogenic | -1.685 | Destabilizing | 0.842 | D | 0.374 | neutral | None | None | None | None | N |
| L/H | 0.4156 | ambiguous | 0.6084 | pathogenic | -0.956 | Destabilizing | 0.998 | D | 0.395 | neutral | None | None | None | None | N |
| L/I | 0.0931 | likely_benign | 0.105 | benign | -0.845 | Destabilizing | 0.525 | D | 0.319 | neutral | None | None | None | None | N |
| L/K | 0.4531 | ambiguous | 0.6092 | pathogenic | -0.771 | Destabilizing | 0.915 | D | 0.341 | neutral | None | None | None | None | N |
| L/M | 0.1633 | likely_benign | 0.1947 | benign | -0.629 | Destabilizing | 0.966 | D | 0.425 | neutral | N | 0.465330255 | None | None | N |
| L/N | 0.6014 | likely_pathogenic | 0.7391 | pathogenic | -0.597 | Destabilizing | 0.991 | D | 0.423 | neutral | None | None | None | None | N |
| L/P | 0.4879 | ambiguous | 0.6828 | pathogenic | -1.012 | Destabilizing | 0.966 | D | 0.421 | neutral | N | 0.46585033 | None | None | N |
| L/Q | 0.3358 | likely_benign | 0.5001 | ambiguous | -0.901 | Destabilizing | 0.989 | D | 0.393 | neutral | N | 0.465503614 | None | None | N |
| L/R | 0.3382 | likely_benign | 0.4926 | ambiguous | -0.187 | Destabilizing | 0.966 | D | 0.392 | neutral | N | 0.46481018 | None | None | N |
| L/S | 0.4522 | ambiguous | 0.6468 | pathogenic | -1.153 | Destabilizing | 0.728 | D | 0.361 | neutral | None | None | None | None | N |
| L/T | 0.3491 | ambiguous | 0.4963 | ambiguous | -1.091 | Destabilizing | 0.842 | D | 0.336 | neutral | None | None | None | None | N |
| L/V | 0.1028 | likely_benign | 0.1203 | benign | -1.012 | Destabilizing | 0.002 | N | 0.089 | neutral | N | 0.431193465 | None | None | N |
| L/W | 0.4128 | ambiguous | 0.5483 | ambiguous | -1.37 | Destabilizing | 0.998 | D | 0.382 | neutral | None | None | None | None | N |
| L/Y | 0.4966 | ambiguous | 0.6246 | pathogenic | -1.086 | Destabilizing | 0.904 | D | 0.36 | 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.