Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14098 | 42517;42518;42519 | chr2:178634489;178634488;178634487 | chr2:179499216;179499215;179499214 |
| N2AB | 12457 | 37594;37595;37596 | chr2:178634489;178634488;178634487 | chr2:179499216;179499215;179499214 |
| N2A | 11530 | 34813;34814;34815 | chr2:178634489;178634488;178634487 | chr2:179499216;179499215;179499214 |
| N2B | 5033 | 15322;15323;15324 | chr2:178634489;178634488;178634487 | chr2:179499216;179499215;179499214 |
| Novex-1 | 5158 | 15697;15698;15699 | chr2:178634489;178634488;178634487 | chr2:179499216;179499215;179499214 |
| Novex-2 | 5225 | 15898;15899;15900 | chr2:178634489;178634488;178634487 | chr2:179499216;179499215;179499214 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/C | rs761607459  |
-2.355 | 0.999 | N | 0.547 | 0.55 | 0.791778486281 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.59E-05 | None | 0 | None | 0 | 0 | 0 |
| F/C | rs761607459 |
-2.355 | 0.999 | N | 0.547 | 0.55 | 0.791778486281 | gnomAD-4.0.0 | 3.18461E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77731E-05 | None | 0 | 0 | 0 | 1.43332E-05 | 0 |
| F/L | rs764819276 |
-1.713 | 0.826 | N | 0.518 | 0.392 | 0.276898752692 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| F/L | rs764819276 |
-1.713 | 0.826 | N | 0.518 | 0.392 | 0.276898752692 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| F/L | rs764819276 |
-1.713 | 0.826 | N | 0.518 | 0.392 | 0.276898752692 | gnomAD-4.0.0 | 4.33918E-06 | None | None | None | None | N | None | 0 | 1.66767E-05 | None | 0 | 0 | None | 0 | 0 | 5.08696E-06 | 0 | 0 |
| F/S | None | None | 0.959 | N | 0.545 | 0.478 | 0.787347168989 | gnomAD-4.0.0 | 4.77692E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.58025E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.8357 | likely_pathogenic | 0.894 | pathogenic | -2.752 | Highly Destabilizing | 0.969 | D | 0.543 | neutral | None | None | None | None | N |
| F/C | 0.4693 | ambiguous | 0.5704 | pathogenic | -2.062 | Highly Destabilizing | 0.999 | D | 0.547 | neutral | N | 0.513221545 | None | None | N |
| F/D | 0.9709 | likely_pathogenic | 0.982 | pathogenic | -2.329 | Highly Destabilizing | 0.991 | D | 0.604 | neutral | None | None | None | None | N |
| F/E | 0.9678 | likely_pathogenic | 0.9788 | pathogenic | -2.17 | Highly Destabilizing | 0.939 | D | 0.602 | neutral | None | None | None | None | N |
| F/G | 0.9521 | likely_pathogenic | 0.9699 | pathogenic | -3.177 | Highly Destabilizing | 0.969 | D | 0.591 | neutral | None | None | None | None | N |
| F/H | 0.7247 | likely_pathogenic | 0.7446 | pathogenic | -1.603 | Destabilizing | 0.046 | N | 0.295 | neutral | None | None | None | None | N |
| F/I | 0.4579 | ambiguous | 0.547 | ambiguous | -1.406 | Destabilizing | 0.959 | D | 0.561 | neutral | N | 0.488236178 | None | None | N |
| F/K | 0.9678 | likely_pathogenic | 0.9757 | pathogenic | -1.978 | Destabilizing | 0.991 | D | 0.603 | neutral | None | None | None | None | N |
| F/L | 0.9515 | likely_pathogenic | 0.9562 | pathogenic | -1.406 | Destabilizing | 0.826 | D | 0.518 | neutral | N | 0.501000697 | None | None | N |
| F/M | 0.7628 | likely_pathogenic | 0.816 | pathogenic | -1.23 | Destabilizing | 0.997 | D | 0.541 | neutral | None | None | None | None | N |
| F/N | 0.8781 | likely_pathogenic | 0.8951 | pathogenic | -2.231 | Highly Destabilizing | 0.982 | D | 0.603 | neutral | None | None | None | None | N |
| F/P | 0.9986 | likely_pathogenic | 0.9992 | pathogenic | -1.859 | Destabilizing | 0.997 | D | 0.635 | neutral | None | None | None | None | N |
| F/Q | 0.9424 | likely_pathogenic | 0.9564 | pathogenic | -2.245 | Highly Destabilizing | 0.991 | D | 0.628 | neutral | None | None | None | None | N |
| F/R | 0.9251 | likely_pathogenic | 0.9418 | pathogenic | -1.361 | Destabilizing | 0.991 | D | 0.621 | neutral | None | None | None | None | N |
| F/S | 0.7835 | likely_pathogenic | 0.845 | pathogenic | -3.042 | Highly Destabilizing | 0.959 | D | 0.545 | neutral | N | 0.510384922 | None | None | N |
| F/T | 0.761 | likely_pathogenic | 0.8224 | pathogenic | -2.77 | Highly Destabilizing | 0.991 | D | 0.553 | neutral | None | None | None | None | N |
| F/V | 0.4114 | ambiguous | 0.4815 | ambiguous | -1.859 | Destabilizing | 0.92 | D | 0.519 | neutral | N | 0.488746398 | None | None | N |
| F/W | 0.5674 | likely_pathogenic | 0.5871 | pathogenic | -0.593 | Destabilizing | 0.991 | D | 0.532 | neutral | None | None | None | None | N |
| F/Y | 0.1293 | likely_benign | 0.1332 | benign | -0.896 | Destabilizing | 0.021 | N | 0.161 | neutral | N | 0.366355192 | 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.