Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 8314 | 25165;25166;25167 | chr2:178718066;178718065;178718064 | chr2:179582793;179582792;179582791 |
| N2AB | 7997 | 24214;24215;24216 | chr2:178718066;178718065;178718064 | chr2:179582793;179582792;179582791 |
| N2A | 7070 | 21433;21434;21435 | chr2:178718066;178718065;178718064 | chr2:179582793;179582792;179582791 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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/L | rs570367600  |
-1.189 | 0.014 | N | 0.321 | 0.263 | 0.251116650651 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.57E-05 | None | 9.8E-05 | None | 0 | 0 | 0 |
| F/L | rs570367600 |
-1.189 | 0.014 | N | 0.321 | 0.263 | 0.251116650651 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07125E-04 | 0 |
| F/L | rs570367600 |
-1.189 | 0.014 | N | 0.321 | 0.263 | 0.251116650651 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| F/L | rs570367600 |
-1.189 | 0.014 | N | 0.321 | 0.263 | 0.251116650651 | gnomAD-4.0.0 | 1.11405E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.773E-05 | None | 0 | 0 | 0 | 8.59747E-05 | 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 | 0.9538 | likely_pathogenic | 0.9738 | pathogenic | -2.19 | Highly Destabilizing | 0.935 | D | 0.655 | neutral | None | None | None | None | N |
| F/C | 0.8497 | likely_pathogenic | 0.9046 | pathogenic | -1.072 | Destabilizing | 0.999 | D | 0.678 | prob.neutral | N | 0.495011627 | None | None | N |
| F/D | 0.9809 | likely_pathogenic | 0.9888 | pathogenic | -1.022 | Destabilizing | 0.981 | D | 0.709 | prob.delet. | None | None | None | None | N |
| F/E | 0.9711 | likely_pathogenic | 0.9827 | pathogenic | -0.935 | Destabilizing | 0.684 | D | 0.697 | prob.neutral | None | None | None | None | N |
| F/G | 0.9725 | likely_pathogenic | 0.9851 | pathogenic | -2.531 | Highly Destabilizing | 0.99 | D | 0.699 | prob.neutral | None | None | None | None | N |
| F/H | 0.876 | likely_pathogenic | 0.9213 | pathogenic | -0.833 | Destabilizing | 0.938 | D | 0.649 | neutral | None | None | None | None | N |
| F/I | 0.6204 | likely_pathogenic | 0.7089 | pathogenic | -1.166 | Destabilizing | 0.693 | D | 0.585 | neutral | N | 0.50769974 | None | None | N |
| F/K | 0.97 | likely_pathogenic | 0.9829 | pathogenic | -1.28 | Destabilizing | 0.913 | D | 0.699 | prob.neutral | None | None | None | None | N |
| F/L | 0.9472 | likely_pathogenic | 0.9669 | pathogenic | -1.166 | Destabilizing | 0.014 | N | 0.321 | neutral | N | 0.495674592 | None | None | N |
| F/M | 0.7824 | likely_pathogenic | 0.8421 | pathogenic | -0.823 | Destabilizing | 0.662 | D | 0.636 | neutral | None | None | None | None | N |
| F/N | 0.9338 | likely_pathogenic | 0.9579 | pathogenic | -1.336 | Destabilizing | 0.99 | D | 0.709 | prob.delet. | None | None | None | None | N |
| F/P | 0.9984 | likely_pathogenic | 0.9991 | pathogenic | -1.502 | Destabilizing | 0.997 | D | 0.702 | prob.neutral | None | None | None | None | N |
| F/Q | 0.9396 | likely_pathogenic | 0.9657 | pathogenic | -1.407 | Destabilizing | 0.281 | N | 0.543 | neutral | None | None | None | None | N |
| F/R | 0.9424 | likely_pathogenic | 0.9659 | pathogenic | -0.622 | Destabilizing | 0.954 | D | 0.71 | prob.delet. | None | None | None | None | N |
| F/S | 0.9209 | likely_pathogenic | 0.9531 | pathogenic | -2.103 | Highly Destabilizing | 0.916 | D | 0.693 | prob.neutral | N | 0.484649522 | None | None | N |
| F/T | 0.9264 | likely_pathogenic | 0.9544 | pathogenic | -1.923 | Destabilizing | 0.99 | D | 0.696 | prob.neutral | None | None | None | None | N |
| F/V | 0.6604 | likely_pathogenic | 0.7484 | pathogenic | -1.502 | Destabilizing | 0.621 | D | 0.583 | neutral | N | 0.488996549 | None | None | N |
| F/W | 0.6341 | likely_pathogenic | 0.7062 | pathogenic | -0.356 | Destabilizing | 0.998 | D | 0.627 | neutral | None | None | None | None | N |
| F/Y | 0.2899 | likely_benign | 0.3397 | benign | -0.575 | Destabilizing | 0.026 | N | 0.356 | neutral | N | 0.45690556 | 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.