Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23076 | 69451;69452;69453 | chr2:178577109;178577108;178577107 | chr2:179441836;179441835;179441834 |
| N2AB | 21435 | 64528;64529;64530 | chr2:178577109;178577108;178577107 | chr2:179441836;179441835;179441834 |
| N2A | 20508 | 61747;61748;61749 | chr2:178577109;178577108;178577107 | chr2:179441836;179441835;179441834 |
| N2B | 14011 | 42256;42257;42258 | chr2:178577109;178577108;178577107 | chr2:179441836;179441835;179441834 |
| Novex-1 | 14136 | 42631;42632;42633 | chr2:178577109;178577108;178577107 | chr2:179441836;179441835;179441834 |
| Novex-2 | 14203 | 42832;42833;42834 | chr2:178577109;178577108;178577107 | chr2:179441836;179441835;179441834 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | None | None | 0.317 | N | 0.595 | 0.151 | 0.315609569513 | gnomAD-4.0.0 | 1.36875E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.52525E-05 | None | 0 | 0 | 0 | 1.15955E-05 | 0 |
| I/T | rs765930349  |
-2.471 | 0.002 | N | 0.336 | 0.087 | 0.532168211543 | gnomAD-2.1.1 | 2.42E-05 | None | None | None | None | I | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 4.45E-05 | 0 |
| I/T | rs765930349 |
-2.471 | 0.002 | N | 0.336 | 0.087 | 0.532168211543 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| I/T | rs765930349 |
-2.471 | 0.002 | N | 0.336 | 0.087 | 0.532168211543 | gnomAD-4.0.0 | 1.30178E-05 | None | None | None | None | I | None | 4.00759E-05 | 0 | None | 0 | 0 | None | 3.12568E-05 | 0 | 1.35644E-05 | 0 | 0 |
| I/V | rs1203126727 |
-1.594 | None | N | 0.172 | 0.044 | 0.233150807113 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| I/V | rs1203126727 |
-1.594 | None | N | 0.172 | 0.044 | 0.233150807113 | gnomAD-4.0.0 | 8.21248E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.07955E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.3342 | likely_benign | 0.3112 | benign | -2.508 | Highly Destabilizing | 0.035 | N | 0.507 | neutral | None | None | None | None | I |
| I/C | 0.4983 | ambiguous | 0.4734 | ambiguous | -1.863 | Destabilizing | 0.824 | D | 0.596 | neutral | None | None | None | None | I |
| I/D | 0.7569 | likely_pathogenic | 0.7309 | pathogenic | -2.441 | Highly Destabilizing | 0.38 | N | 0.641 | neutral | None | None | None | None | I |
| I/E | 0.5692 | likely_pathogenic | 0.5529 | ambiguous | -2.299 | Highly Destabilizing | 0.38 | N | 0.648 | neutral | None | None | None | None | I |
| I/F | 0.1647 | likely_benign | 0.1579 | benign | -1.54 | Destabilizing | 0.38 | N | 0.607 | neutral | None | None | None | None | I |
| I/G | 0.6514 | likely_pathogenic | 0.6268 | pathogenic | -2.966 | Highly Destabilizing | 0.149 | N | 0.649 | neutral | None | None | None | None | I |
| I/H | 0.4211 | ambiguous | 0.3984 | ambiguous | -2.134 | Highly Destabilizing | 0.935 | D | 0.649 | neutral | None | None | None | None | I |
| I/K | 0.4218 | ambiguous | 0.4023 | ambiguous | -1.849 | Destabilizing | 0.317 | N | 0.645 | neutral | N | 0.47877139 | None | None | I |
| I/L | 0.1101 | likely_benign | 0.1069 | benign | -1.221 | Destabilizing | None | N | 0.189 | neutral | N | 0.513264983 | None | None | I |
| I/M | 0.1144 | likely_benign | 0.1106 | benign | -1.165 | Destabilizing | 0.317 | N | 0.595 | neutral | N | 0.500829345 | None | None | I |
| I/N | 0.3115 | likely_benign | 0.2895 | benign | -1.975 | Destabilizing | 0.38 | N | 0.64 | neutral | None | None | None | None | I |
| I/P | 0.9794 | likely_pathogenic | 0.9771 | pathogenic | -1.628 | Destabilizing | 0.555 | D | 0.642 | neutral | None | None | None | None | I |
| I/Q | 0.4036 | ambiguous | 0.3832 | ambiguous | -2.0 | Highly Destabilizing | 0.555 | D | 0.647 | neutral | None | None | None | None | I |
| I/R | 0.3178 | likely_benign | 0.3137 | benign | -1.348 | Destabilizing | 0.484 | N | 0.633 | neutral | N | 0.473642828 | None | None | I |
| I/S | 0.252 | likely_benign | 0.2397 | benign | -2.703 | Highly Destabilizing | 0.081 | N | 0.581 | neutral | None | None | None | None | I |
| I/T | 0.1428 | likely_benign | 0.1334 | benign | -2.433 | Highly Destabilizing | 0.002 | N | 0.336 | neutral | N | 0.485982381 | None | None | I |
| I/V | 0.0606 | likely_benign | 0.0601 | benign | -1.628 | Destabilizing | None | N | 0.172 | neutral | N | 0.451389805 | None | None | I |
| I/W | 0.7663 | likely_pathogenic | 0.7555 | pathogenic | -1.752 | Destabilizing | 0.935 | D | 0.667 | neutral | None | None | None | None | I |
| I/Y | 0.4472 | ambiguous | 0.4361 | ambiguous | -1.537 | Destabilizing | 0.555 | D | 0.611 | 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.