Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19562 | 58909;58910;58911 | chr2:178593616;178593615;178593614 | chr2:179458343;179458342;179458341 |
| N2AB | 17921 | 53986;53987;53988 | chr2:178593616;178593615;178593614 | chr2:179458343;179458342;179458341 |
| N2A | 16994 | 51205;51206;51207 | chr2:178593616;178593615;178593614 | chr2:179458343;179458342;179458341 |
| N2B | 10497 | 31714;31715;31716 | chr2:178593616;178593615;178593614 | chr2:179458343;179458342;179458341 |
| Novex-1 | 10622 | 32089;32090;32091 | chr2:178593616;178593615;178593614 | chr2:179458343;179458342;179458341 |
| Novex-2 | 10689 | 32290;32291;32292 | chr2:178593616;178593615;178593614 | chr2:179458343;179458342;179458341 |
| 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/L | rs397517637  |
-1.113 | 0.031 | N | 0.267 | 0.121 | 0.44318313171 | gnomAD-2.1.1 | 7.18E-06 | None | None | None | None | I | None | 8.28E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/L | rs397517637 |
-1.113 | 0.031 | N | 0.267 | 0.121 | 0.44318313171 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/L | rs397517637 |
-1.113 | 0.031 | N | 0.267 | 0.121 | 0.44318313171 | gnomAD-4.0.0 | 6.57272E-06 | None | None | None | None | I | None | 2.41161E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/R | None | None | 0.879 | N | 0.82 | 0.374 | 0.67247961064 | gnomAD-4.0.0 | 4.80129E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.25001E-06 | 0 | 0 |
| I/V | rs397517637 |
None | 0.001 | N | 0.223 | 0.115 | 0.384919354899 | gnomAD-4.0.0 | 6.00164E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.25002E-06 | 0 | 3.66327E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.5259 | ambiguous | 0.5395 | ambiguous | -1.677 | Destabilizing | 0.404 | N | 0.635 | neutral | None | None | None | None | I |
| I/C | 0.7087 | likely_pathogenic | 0.7239 | pathogenic | -0.886 | Destabilizing | 0.973 | D | 0.751 | deleterious | None | None | None | None | I |
| I/D | 0.801 | likely_pathogenic | 0.8106 | pathogenic | -1.16 | Destabilizing | 0.967 | D | 0.821 | deleterious | None | None | None | None | I |
| I/E | 0.6912 | likely_pathogenic | 0.7127 | pathogenic | -1.203 | Destabilizing | 0.906 | D | 0.813 | deleterious | None | None | None | None | I |
| I/F | 0.2451 | likely_benign | 0.2569 | benign | -1.391 | Destabilizing | 0.826 | D | 0.701 | prob.neutral | None | None | None | None | I |
| I/G | 0.7941 | likely_pathogenic | 0.8069 | pathogenic | -1.959 | Destabilizing | 0.906 | D | 0.803 | deleterious | None | None | None | None | I |
| I/H | 0.6587 | likely_pathogenic | 0.6743 | pathogenic | -1.113 | Destabilizing | 0.991 | D | 0.82 | deleterious | None | None | None | None | I |
| I/K | 0.4326 | ambiguous | 0.4473 | ambiguous | -1.017 | Destabilizing | 0.782 | D | 0.807 | deleterious | N | 0.489097257 | None | None | I |
| I/L | 0.1718 | likely_benign | 0.1747 | benign | -0.991 | Destabilizing | 0.031 | N | 0.267 | neutral | N | 0.446133127 | None | None | I |
| I/M | 0.1662 | likely_benign | 0.1705 | benign | -0.623 | Destabilizing | 0.174 | N | 0.403 | neutral | N | 0.48819318 | None | None | I |
| I/N | 0.3799 | ambiguous | 0.3903 | ambiguous | -0.715 | Destabilizing | 0.906 | D | 0.822 | deleterious | None | None | None | None | I |
| I/P | 0.7356 | likely_pathogenic | 0.7715 | pathogenic | -1.189 | Destabilizing | 0.967 | D | 0.821 | deleterious | None | None | None | None | I |
| I/Q | 0.572 | likely_pathogenic | 0.595 | pathogenic | -0.992 | Destabilizing | 0.906 | D | 0.823 | deleterious | None | None | None | None | I |
| I/R | 0.3825 | ambiguous | 0.3901 | ambiguous | -0.316 | Destabilizing | 0.879 | D | 0.82 | deleterious | N | 0.485056875 | None | None | I |
| I/S | 0.4471 | ambiguous | 0.4602 | ambiguous | -1.296 | Destabilizing | 0.826 | D | 0.766 | deleterious | None | None | None | None | I |
| I/T | 0.375 | ambiguous | 0.3863 | ambiguous | -1.229 | Destabilizing | 0.505 | D | 0.684 | prob.neutral | N | 0.47510924 | None | None | I |
| I/V | 0.1012 | likely_benign | 0.0986 | benign | -1.189 | Destabilizing | 0.001 | N | 0.223 | neutral | N | 0.426643289 | None | None | I |
| I/W | 0.8496 | likely_pathogenic | 0.8661 | pathogenic | -1.383 | Destabilizing | 0.991 | D | 0.823 | deleterious | None | None | None | None | I |
| I/Y | 0.593 | likely_pathogenic | 0.613 | pathogenic | -1.189 | Destabilizing | 0.906 | D | 0.755 | deleterious | 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.