Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28088 | 84487;84488;84489 | chr2:178561870;178561869;178561868 | chr2:179426597;179426596;179426595 |
| N2AB | 26447 | 79564;79565;79566 | chr2:178561870;178561869;178561868 | chr2:179426597;179426596;179426595 |
| N2A | 25520 | 76783;76784;76785 | chr2:178561870;178561869;178561868 | chr2:179426597;179426596;179426595 |
| N2B | 19023 | 57292;57293;57294 | chr2:178561870;178561869;178561868 | chr2:179426597;179426596;179426595 |
| Novex-1 | 19148 | 57667;57668;57669 | chr2:178561870;178561869;178561868 | chr2:179426597;179426596;179426595 |
| Novex-2 | 19215 | 57868;57869;57870 | chr2:178561870;178561869;178561868 | chr2:179426597;179426596;179426595 |
| 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/N | rs200450022  |
-0.066 | 0.004 | N | 0.073 | 0.057 | None | gnomAD-2.1.1 | 5.93633E-04 | None | None | None | None | I | None | 2.06697E-04 | 3.39924E-04 | None | 0 | 0 | None | 0 | None | 7.2023E-04 | 1.00997E-03 | 2.81294E-04 |
| S/N | rs200450022 |
-0.066 | 0.004 | N | 0.073 | 0.057 | None | gnomAD-3.1.2 | 6.11199E-04 | None | None | None | None | I | None | 1.44781E-04 | 1.96489E-04 | 0 | 0 | 0 | None | 7.5358E-04 | 0 | 1.10262E-03 | 0 | 4.78011E-04 |
| S/N | rs200450022 |
-0.066 | 0.004 | N | 0.073 | 0.057 | None | 1000 genomes | 5.99042E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 3E-03 | None | None | None | 0 | None |
| S/N | rs200450022 |
-0.066 | 0.004 | N | 0.073 | 0.057 | None | gnomAD-4.0.0 | 1.23634E-03 | None | None | None | None | I | None | 1.4662E-04 | 4.33391E-04 | None | 0 | 0 | None | 7.6584E-04 | 0 | 1.56984E-03 | 0 | 9.1235E-04 |
| S/T | rs200450022 |
None | 0.472 | N | 0.342 | 0.127 | 0.266385636622 | gnomAD-4.0.0 | 6.84295E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.52487E-05 | None | 0 | 0 | 0 | 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 | 0.1829 | likely_benign | 0.1633 | benign | -0.546 | Destabilizing | 0.543 | D | 0.426 | neutral | None | None | None | None | I |
| S/C | 0.194 | likely_benign | 0.1818 | benign | -0.407 | Destabilizing | 0.994 | D | 0.421 | neutral | N | 0.488284952 | None | None | I |
| S/D | 0.7754 | likely_pathogenic | 0.756 | pathogenic | -0.347 | Destabilizing | 0.373 | N | 0.313 | neutral | None | None | None | None | I |
| S/E | 0.8824 | likely_pathogenic | 0.8678 | pathogenic | -0.42 | Destabilizing | 0.373 | N | 0.346 | neutral | None | None | None | None | I |
| S/F | 0.6227 | likely_pathogenic | 0.5938 | pathogenic | -0.984 | Destabilizing | 0.984 | D | 0.405 | neutral | None | None | None | None | I |
| S/G | 0.1475 | likely_benign | 0.125 | benign | -0.705 | Destabilizing | 0.472 | N | 0.383 | neutral | N | 0.479473087 | None | None | I |
| S/H | 0.6241 | likely_pathogenic | 0.6017 | pathogenic | -1.237 | Destabilizing | 0.953 | D | 0.407 | neutral | None | None | None | None | I |
| S/I | 0.405 | ambiguous | 0.3833 | ambiguous | -0.249 | Destabilizing | 0.939 | D | 0.423 | neutral | N | 0.506648442 | None | None | I |
| S/K | 0.9067 | likely_pathogenic | 0.892 | pathogenic | -0.745 | Destabilizing | 0.59 | D | 0.311 | neutral | None | None | None | None | I |
| S/L | 0.2136 | likely_benign | 0.2014 | benign | -0.249 | Destabilizing | 0.742 | D | 0.397 | neutral | None | None | None | None | I |
| S/M | 0.3589 | ambiguous | 0.3526 | ambiguous | 0.137 | Stabilizing | 0.953 | D | 0.404 | neutral | None | None | None | None | I |
| S/N | 0.1676 | likely_benign | 0.1564 | benign | -0.533 | Destabilizing | 0.004 | N | 0.073 | neutral | N | 0.474864098 | None | None | I |
| S/P | 0.8694 | likely_pathogenic | 0.8218 | pathogenic | -0.318 | Destabilizing | 0.953 | D | 0.419 | neutral | None | None | None | None | I |
| S/Q | 0.7609 | likely_pathogenic | 0.7549 | pathogenic | -0.833 | Destabilizing | 0.037 | N | 0.188 | neutral | None | None | None | None | I |
| S/R | 0.8673 | likely_pathogenic | 0.8539 | pathogenic | -0.468 | Destabilizing | 0.521 | D | 0.371 | neutral | N | 0.46865976 | None | None | I |
| S/T | 0.0928 | likely_benign | 0.0935 | benign | -0.597 | Destabilizing | 0.472 | N | 0.342 | neutral | N | 0.406924165 | None | None | I |
| S/V | 0.425 | ambiguous | 0.4094 | ambiguous | -0.318 | Destabilizing | 0.742 | D | 0.386 | neutral | None | None | None | None | I |
| S/W | 0.711 | likely_pathogenic | 0.6834 | pathogenic | -0.946 | Destabilizing | 0.996 | D | 0.571 | neutral | None | None | None | None | I |
| S/Y | 0.4998 | ambiguous | 0.4532 | ambiguous | -0.699 | Destabilizing | 0.984 | D | 0.421 | neutral | None | None | None | None | I |
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.