Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28656 | 86191;86192;86193 | chr2:178560166;178560165;178560164 | chr2:179424893;179424892;179424891 |
| N2AB | 27015 | 81268;81269;81270 | chr2:178560166;178560165;178560164 | chr2:179424893;179424892;179424891 |
| N2A | 26088 | 78487;78488;78489 | chr2:178560166;178560165;178560164 | chr2:179424893;179424892;179424891 |
| N2B | 19591 | 58996;58997;58998 | chr2:178560166;178560165;178560164 | chr2:179424893;179424892;179424891 |
| Novex-1 | 19716 | 59371;59372;59373 | chr2:178560166;178560165;178560164 | chr2:179424893;179424892;179424891 |
| Novex-2 | 19783 | 59572;59573;59574 | chr2:178560166;178560165;178560164 | chr2:179424893;179424892;179424891 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/F | rs1703122719  |
None | 0.939 | N | 0.631 | 0.342 | 0.638346370533 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/F | rs1703122719 |
None | 0.939 | N | 0.631 | 0.342 | 0.638346370533 | gnomAD-4.0.0 | 6.57471E-06 | None | None | None | None | N | None | 0 | 6.55308E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/T | None | None | 0.003 | N | 0.098 | 0.036 | 0.117506650769 | gnomAD-4.0.0 | 2.05273E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69854E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0816 | likely_benign | 0.0763 | benign | -0.622 | Destabilizing | 0.012 | N | 0.097 | neutral | N | 0.448274929 | None | None | N |
| S/C | 0.1181 | likely_benign | 0.1099 | benign | -0.491 | Destabilizing | 0.994 | D | 0.525 | neutral | N | 0.487159316 | None | None | N |
| S/D | 0.7936 | likely_pathogenic | 0.777 | pathogenic | -0.908 | Destabilizing | 0.59 | D | 0.452 | neutral | None | None | None | None | N |
| S/E | 0.8008 | likely_pathogenic | 0.7969 | pathogenic | -0.838 | Destabilizing | 0.742 | D | 0.439 | neutral | None | None | None | None | N |
| S/F | 0.3522 | ambiguous | 0.3255 | benign | -0.565 | Destabilizing | 0.939 | D | 0.631 | neutral | N | 0.474789053 | None | None | N |
| S/G | 0.0927 | likely_benign | 0.0881 | benign | -0.949 | Destabilizing | 0.373 | N | 0.421 | neutral | None | None | None | None | N |
| S/H | 0.6523 | likely_pathogenic | 0.6476 | pathogenic | -1.547 | Destabilizing | 0.953 | D | 0.535 | neutral | None | None | None | None | N |
| S/I | 0.2709 | likely_benign | 0.2216 | benign | 0.161 | Stabilizing | 0.91 | D | 0.619 | neutral | None | None | None | None | N |
| S/K | 0.9035 | likely_pathogenic | 0.9057 | pathogenic | -0.801 | Destabilizing | 0.742 | D | 0.443 | neutral | None | None | None | None | N |
| S/L | 0.1293 | likely_benign | 0.1134 | benign | 0.161 | Stabilizing | 0.59 | D | 0.576 | neutral | None | None | None | None | N |
| S/M | 0.2523 | likely_benign | 0.2173 | benign | 0.299 | Stabilizing | 0.984 | D | 0.531 | neutral | None | None | None | None | N |
| S/N | 0.2802 | likely_benign | 0.2484 | benign | -0.995 | Destabilizing | 0.009 | N | 0.294 | neutral | None | None | None | None | N |
| S/P | 0.3826 | ambiguous | 0.367 | ambiguous | -0.064 | Destabilizing | 0.939 | D | 0.542 | neutral | N | 0.470269602 | None | None | N |
| S/Q | 0.696 | likely_pathogenic | 0.6851 | pathogenic | -0.976 | Destabilizing | 0.953 | D | 0.496 | neutral | None | None | None | None | N |
| S/R | 0.8581 | likely_pathogenic | 0.863 | pathogenic | -0.919 | Destabilizing | 0.91 | D | 0.549 | neutral | None | None | None | None | N |
| S/T | 0.1 | likely_benign | 0.0916 | benign | -0.791 | Destabilizing | 0.003 | N | 0.098 | neutral | N | 0.493583144 | None | None | N |
| S/V | 0.2209 | likely_benign | 0.1764 | benign | -0.064 | Destabilizing | 0.59 | D | 0.585 | neutral | None | None | None | None | N |
| S/W | 0.5639 | ambiguous | 0.5649 | pathogenic | -0.704 | Destabilizing | 0.996 | D | 0.683 | prob.neutral | None | None | None | None | N |
| S/Y | 0.3704 | ambiguous | 0.3643 | ambiguous | -0.371 | Destabilizing | 0.979 | D | 0.637 | neutral | N | 0.469219645 | 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.