Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29774 | 89545;89546;89547 | chr2:178553685;178553684;178553683 | chr2:179418412;179418411;179418410 |
| N2AB | 28133 | 84622;84623;84624 | chr2:178553685;178553684;178553683 | chr2:179418412;179418411;179418410 |
| N2A | 27206 | 81841;81842;81843 | chr2:178553685;178553684;178553683 | chr2:179418412;179418411;179418410 |
| N2B | 20709 | 62350;62351;62352 | chr2:178553685;178553684;178553683 | chr2:179418412;179418411;179418410 |
| Novex-1 | 20834 | 62725;62726;62727 | chr2:178553685;178553684;178553683 | chr2:179418412;179418411;179418410 |
| Novex-2 | 20901 | 62926;62927;62928 | chr2:178553685;178553684;178553683 | chr2:179418412;179418411;179418410 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/K | rs750672440  |
-1.432 | None | N | 0.147 | 0.094 | None | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 1.14758E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/K | rs750672440 |
-1.432 | None | N | 0.147 | 0.094 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 1.20592E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/K | rs750672440 |
-1.432 | None | N | 0.147 | 0.094 | None | gnomAD-4.0.0 | 6.19669E-06 | None | None | None | None | N | None | 1.20099E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 8.4758E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.6359 | likely_pathogenic | 0.5598 | ambiguous | -1.861 | Destabilizing | 0.016 | N | 0.426 | neutral | None | None | None | None | N |
| R/C | 0.1743 | likely_benign | 0.1453 | benign | -1.696 | Destabilizing | 0.864 | D | 0.621 | neutral | None | None | None | None | N |
| R/D | 0.9383 | likely_pathogenic | 0.9132 | pathogenic | -0.6 | Destabilizing | 0.072 | N | 0.645 | neutral | None | None | None | None | N |
| R/E | 0.6127 | likely_pathogenic | 0.5646 | pathogenic | -0.388 | Destabilizing | 0.038 | N | 0.5 | neutral | None | None | None | None | N |
| R/F | 0.7159 | likely_pathogenic | 0.6682 | pathogenic | -1.096 | Destabilizing | 0.214 | N | 0.652 | neutral | None | None | None | None | N |
| R/G | 0.5372 | ambiguous | 0.458 | ambiguous | -2.228 | Highly Destabilizing | 0.055 | N | 0.557 | neutral | N | 0.496629517 | None | None | N |
| R/H | 0.1843 | likely_benign | 0.1691 | benign | -1.984 | Destabilizing | 0.356 | N | 0.561 | neutral | None | None | None | None | N |
| R/I | 0.4319 | ambiguous | 0.3725 | ambiguous | -0.804 | Destabilizing | 0.029 | N | 0.565 | neutral | N | 0.511517768 | None | None | N |
| R/K | 0.112 | likely_benign | 0.1106 | benign | -1.231 | Destabilizing | None | N | 0.147 | neutral | N | 0.464743104 | None | None | N |
| R/L | 0.2928 | likely_benign | 0.2477 | benign | -0.804 | Destabilizing | None | N | 0.325 | neutral | None | None | None | None | N |
| R/M | 0.3703 | ambiguous | 0.317 | benign | -1.239 | Destabilizing | 0.003 | N | 0.263 | neutral | None | None | None | None | N |
| R/N | 0.8299 | likely_pathogenic | 0.7808 | pathogenic | -1.081 | Destabilizing | 0.072 | N | 0.525 | neutral | None | None | None | None | N |
| R/P | 0.9749 | likely_pathogenic | 0.9619 | pathogenic | -1.143 | Destabilizing | 0.356 | N | 0.648 | neutral | None | None | None | None | N |
| R/Q | 0.1174 | likely_benign | 0.1064 | benign | -1.046 | Destabilizing | 0.038 | N | 0.509 | neutral | None | None | None | None | N |
| R/S | 0.7447 | likely_pathogenic | 0.6691 | pathogenic | -2.08 | Highly Destabilizing | 0.029 | N | 0.521 | neutral | D | 0.52407941 | None | None | N |
| R/T | 0.5186 | ambiguous | 0.4466 | ambiguous | -1.647 | Destabilizing | 0.055 | N | 0.525 | neutral | N | 0.493160024 | None | None | N |
| R/V | 0.5447 | ambiguous | 0.4707 | ambiguous | -1.143 | Destabilizing | 0.016 | N | 0.471 | neutral | None | None | None | None | N |
| R/W | 0.4168 | ambiguous | 0.3524 | ambiguous | -0.524 | Destabilizing | 0.864 | D | 0.643 | neutral | None | None | None | None | N |
| R/Y | 0.6033 | likely_pathogenic | 0.5554 | ambiguous | -0.394 | Destabilizing | 0.628 | D | 0.63 | neutral | None | None | 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.