Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17341 | 52246;52247;52248 | chr2:178609289;178609288;178609287 | chr2:179474016;179474015;179474014 |
| N2AB | 15700 | 47323;47324;47325 | chr2:178609289;178609288;178609287 | chr2:179474016;179474015;179474014 |
| N2A | 14773 | 44542;44543;44544 | chr2:178609289;178609288;178609287 | chr2:179474016;179474015;179474014 |
| N2B | 8276 | 25051;25052;25053 | chr2:178609289;178609288;178609287 | chr2:179474016;179474015;179474014 |
| Novex-1 | 8401 | 25426;25427;25428 | chr2:178609289;178609288;178609287 | chr2:179474016;179474015;179474014 |
| Novex-2 | 8468 | 25627;25628;25629 | chr2:178609289;178609288;178609287 | chr2:179474016;179474015;179474014 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/L | rs370390570  |
0.79 | 0.991 | N | 0.478 | 0.425 | 0.416956310301 | gnomAD-2.1.1 | 8.63E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.89E-05 | 0 |
| R/L | rs370390570 |
0.79 | 0.991 | N | 0.478 | 0.425 | 0.416956310301 | gnomAD-4.0.0 | 2.77426E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.72097E-06 | 1.22043E-05 | 0 |
| R/Q | rs370390570 |
0.45 | 1.0 | N | 0.509 | 0.288 | None | gnomAD-2.1.1 | 1.25401E-04 | None | None | None | None | N | None | 7.52383E-04 | 5.95E-05 | None | 0 | 4.75436E-04 | None | 0 | None | 0 | 3.3E-05 | 0 |
| R/Q | rs370390570 |
0.45 | 1.0 | N | 0.509 | 0.288 | None | gnomAD-3.1.2 | 3.75163E-04 | None | None | None | None | N | None | 1.25592E-03 | 1.97006E-04 | 0 | 0 | 1.9478E-04 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/Q | rs370390570 |
0.45 | 1.0 | N | 0.509 | 0.288 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 1.5E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/Q | rs370390570 |
0.45 | 1.0 | N | 0.509 | 0.288 | None | gnomAD-4.0.0 | 8.09345E-05 | None | None | None | None | N | None | 1.17049E-03 | 1.54682E-04 | None | 0 | 2.47491E-04 | None | 0 | 1.67448E-04 | 1.45239E-05 | 0 | 6.49308E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9854 | likely_pathogenic | 0.9874 | pathogenic | -0.343 | Destabilizing | 0.983 | D | 0.524 | neutral | None | None | None | None | N |
| R/C | 0.9429 | likely_pathogenic | 0.9529 | pathogenic | -0.133 | Destabilizing | 0.296 | N | 0.454 | neutral | None | None | None | None | N |
| R/D | 0.9938 | likely_pathogenic | 0.9939 | pathogenic | 0.015 | Stabilizing | 0.999 | D | 0.532 | neutral | None | None | None | None | N |
| R/E | 0.9609 | likely_pathogenic | 0.9634 | pathogenic | 0.15 | Stabilizing | 0.997 | D | 0.481 | neutral | None | None | None | None | N |
| R/F | 0.9784 | likely_pathogenic | 0.9798 | pathogenic | -0.075 | Destabilizing | 0.999 | D | 0.559 | neutral | None | None | None | None | N |
| R/G | 0.966 | likely_pathogenic | 0.9716 | pathogenic | -0.674 | Destabilizing | 0.996 | D | 0.448 | neutral | N | 0.485521523 | None | None | N |
| R/H | 0.8362 | likely_pathogenic | 0.8555 | pathogenic | -1.264 | Destabilizing | 1.0 | D | 0.494 | neutral | None | None | None | None | N |
| R/I | 0.9288 | likely_pathogenic | 0.9377 | pathogenic | 0.543 | Stabilizing | 0.998 | D | 0.561 | neutral | None | None | None | None | N |
| R/K | 0.6299 | likely_pathogenic | 0.688 | pathogenic | -0.406 | Destabilizing | 0.997 | D | 0.511 | neutral | None | None | None | None | N |
| R/L | 0.8718 | likely_pathogenic | 0.8844 | pathogenic | 0.543 | Stabilizing | 0.991 | D | 0.478 | neutral | N | 0.458841985 | None | None | N |
| R/M | 0.9751 | likely_pathogenic | 0.9794 | pathogenic | 0.102 | Stabilizing | 1.0 | D | 0.493 | neutral | None | None | None | None | N |
| R/N | 0.992 | likely_pathogenic | 0.9926 | pathogenic | 0.073 | Stabilizing | 0.999 | D | 0.493 | neutral | None | None | None | None | N |
| R/P | 0.9562 | likely_pathogenic | 0.959 | pathogenic | 0.27 | Stabilizing | 1.0 | D | 0.526 | neutral | N | 0.497073661 | None | None | N |
| R/Q | 0.7826 | likely_pathogenic | 0.818 | pathogenic | 0.028 | Stabilizing | 1.0 | D | 0.509 | neutral | N | 0.484761054 | None | None | N |
| R/S | 0.9923 | likely_pathogenic | 0.9929 | pathogenic | -0.462 | Destabilizing | 0.992 | D | 0.465 | neutral | None | None | None | None | N |
| R/T | 0.9868 | likely_pathogenic | 0.9892 | pathogenic | -0.144 | Destabilizing | 0.992 | D | 0.471 | neutral | None | None | None | None | N |
| R/V | 0.9626 | likely_pathogenic | 0.9677 | pathogenic | 0.27 | Stabilizing | 0.995 | D | 0.533 | neutral | None | None | None | None | N |
| R/W | 0.878 | likely_pathogenic | 0.8779 | pathogenic | 0.138 | Stabilizing | 1.0 | D | 0.595 | neutral | None | None | None | None | N |
| R/Y | 0.9544 | likely_pathogenic | 0.9562 | pathogenic | 0.437 | Stabilizing | 0.999 | D | 0.527 | 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.