Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23348 | 70267;70268;70269 | chr2:178576090;178576089;178576088 | chr2:179440817;179440816;179440815 |
| N2AB | 21707 | 65344;65345;65346 | chr2:178576090;178576089;178576088 | chr2:179440817;179440816;179440815 |
| N2A | 20780 | 62563;62564;62565 | chr2:178576090;178576089;178576088 | chr2:179440817;179440816;179440815 |
| N2B | 14283 | 43072;43073;43074 | chr2:178576090;178576089;178576088 | chr2:179440817;179440816;179440815 |
| Novex-1 | 14408 | 43447;43448;43449 | chr2:178576090;178576089;178576088 | chr2:179440817;179440816;179440815 |
| Novex-2 | 14475 | 43648;43649;43650 | chr2:178576090;178576089;178576088 | chr2:179440817;179440816;179440815 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/T | rs775146212  |
-0.407 | 0.477 | N | 0.553 | 0.189 | 0.26169431596 | gnomAD-2.1.1 | 1.28616E-04 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.80115E-03 | None | 0 | None | 0 | 0 | 1.40528E-04 |
| A/T | rs775146212 |
-0.407 | 0.477 | N | 0.553 | 0.189 | 0.26169431596 | gnomAD-3.1.2 | 7.89E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 1.93798E-03 | None | 0 | 0 | 0 | 2.07125E-04 | 4.78011E-04 |
| A/T | rs775146212 |
-0.407 | 0.477 | N | 0.553 | 0.189 | 0.26169431596 | gnomAD-4.0.0 | 3.59475E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 9.59993E-04 | None | 0 | 0 | 0 | 1.09813E-04 | 8.00435E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.7268 | likely_pathogenic | 0.6883 | pathogenic | -0.701 | Destabilizing | 0.985 | D | 0.633 | neutral | None | None | None | None | I |
| A/D | 0.7326 | likely_pathogenic | 0.7052 | pathogenic | -0.703 | Destabilizing | 0.864 | D | 0.679 | prob.neutral | D | 0.526496144 | None | None | I |
| A/E | 0.646 | likely_pathogenic | 0.6156 | pathogenic | -0.853 | Destabilizing | 0.894 | D | 0.603 | neutral | None | None | None | None | I |
| A/F | 0.6489 | likely_pathogenic | 0.6403 | pathogenic | -0.966 | Destabilizing | 0.894 | D | 0.687 | prob.neutral | None | None | None | None | I |
| A/G | 0.3106 | likely_benign | 0.2577 | benign | -0.481 | Destabilizing | 0.477 | N | 0.547 | neutral | N | 0.491652852 | None | None | I |
| A/H | 0.7786 | likely_pathogenic | 0.7496 | pathogenic | -0.569 | Destabilizing | 0.995 | D | 0.671 | neutral | None | None | None | None | I |
| A/I | 0.3805 | ambiguous | 0.3867 | ambiguous | -0.39 | Destabilizing | 0.593 | D | 0.599 | neutral | None | None | None | None | I |
| A/K | 0.8162 | likely_pathogenic | 0.7925 | pathogenic | -0.852 | Destabilizing | 0.894 | D | 0.604 | neutral | None | None | None | None | I |
| A/L | 0.3001 | likely_benign | 0.2905 | benign | -0.39 | Destabilizing | 0.547 | D | 0.549 | neutral | None | None | None | None | I |
| A/M | 0.337 | likely_benign | 0.3278 | benign | -0.353 | Destabilizing | 0.97 | D | 0.645 | neutral | None | None | None | None | I |
| A/N | 0.513 | ambiguous | 0.493 | ambiguous | -0.443 | Destabilizing | 0.894 | D | 0.672 | neutral | None | None | None | None | I |
| A/P | 0.4005 | ambiguous | 0.3799 | ambiguous | -0.359 | Destabilizing | 0.928 | D | 0.63 | neutral | N | 0.507641025 | None | None | I |
| A/Q | 0.6347 | likely_pathogenic | 0.5998 | pathogenic | -0.743 | Destabilizing | 0.945 | D | 0.646 | neutral | None | None | None | None | I |
| A/R | 0.7531 | likely_pathogenic | 0.7286 | pathogenic | -0.341 | Destabilizing | 0.894 | D | 0.642 | neutral | None | None | None | None | I |
| A/S | 0.1524 | likely_benign | 0.1456 | benign | -0.628 | Destabilizing | 0.053 | N | 0.357 | neutral | N | 0.486033601 | None | None | I |
| A/T | 0.1613 | likely_benign | 0.153 | benign | -0.705 | Destabilizing | 0.477 | N | 0.553 | neutral | N | 0.512412126 | None | None | I |
| A/V | 0.1752 | likely_benign | 0.189 | benign | -0.359 | Destabilizing | 0.013 | N | 0.356 | neutral | N | 0.477318118 | None | None | I |
| A/W | 0.9101 | likely_pathogenic | 0.8897 | pathogenic | -1.13 | Destabilizing | 0.995 | D | 0.73 | prob.delet. | None | None | None | None | I |
| A/Y | 0.7754 | likely_pathogenic | 0.7311 | pathogenic | -0.789 | Destabilizing | 0.945 | D | 0.684 | prob.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.