Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27105 | 81538;81539;81540 | chr2:178564819;178564818;178564817 | chr2:179429546;179429545;179429544 |
| N2AB | 25464 | 76615;76616;76617 | chr2:178564819;178564818;178564817 | chr2:179429546;179429545;179429544 |
| N2A | 24537 | 73834;73835;73836 | chr2:178564819;178564818;178564817 | chr2:179429546;179429545;179429544 |
| N2B | 18040 | 54343;54344;54345 | chr2:178564819;178564818;178564817 | chr2:179429546;179429545;179429544 |
| Novex-1 | 18165 | 54718;54719;54720 | chr2:178564819;178564818;178564817 | chr2:179429546;179429545;179429544 |
| Novex-2 | 18232 | 54919;54920;54921 | chr2:178564819;178564818;178564817 | chr2:179429546;179429545;179429544 |
| 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 | None | None | None | N | 0.053 | 0.059 | 0.330331372229 | gnomAD-4.0.0 | 1.36912E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79938E-06 | 0 | 0 |
| I/S | None | None | 0.012 | N | 0.303 | 0.144 | 0.413241256734 | gnomAD-4.0.0 | 6.84562E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99698E-07 | 0 | 0 |
| I/T | rs763598647  |
-0.906 | None | N | 0.143 | 0.1 | 0.313818047136 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.01E-06 | 0 |
| I/T | rs763598647 |
-0.906 | None | N | 0.143 | 0.1 | 0.313818047136 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs763598647 |
-0.906 | None | N | 0.143 | 0.1 | 0.313818047136 | gnomAD-4.0.0 | 4.33993E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.9347E-06 | 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 | 0.1507 | likely_benign | 0.1367 | benign | -1.332 | Destabilizing | 0.007 | N | 0.299 | neutral | None | None | None | None | I |
| I/C | 0.5653 | likely_pathogenic | 0.5283 | ambiguous | -0.757 | Destabilizing | 0.356 | N | 0.315 | neutral | None | None | None | None | I |
| I/D | 0.7348 | likely_pathogenic | 0.6786 | pathogenic | -0.892 | Destabilizing | 0.072 | N | 0.393 | neutral | None | None | None | None | I |
| I/E | 0.6019 | likely_pathogenic | 0.5389 | ambiguous | -0.944 | Destabilizing | 0.072 | N | 0.399 | neutral | None | None | None | None | I |
| I/F | 0.1301 | likely_benign | 0.1142 | benign | -1.028 | Destabilizing | 0.029 | N | 0.306 | neutral | N | 0.47407781 | None | None | I |
| I/G | 0.5117 | ambiguous | 0.4837 | ambiguous | -1.591 | Destabilizing | 0.072 | N | 0.362 | neutral | None | None | None | None | I |
| I/H | 0.4166 | ambiguous | 0.3611 | ambiguous | -0.787 | Destabilizing | 0.864 | D | 0.278 | neutral | None | None | None | None | I |
| I/K | 0.3347 | likely_benign | 0.2968 | benign | -0.898 | Destabilizing | 0.072 | N | 0.373 | neutral | None | None | None | None | I |
| I/L | 0.071 | likely_benign | 0.0633 | benign | -0.728 | Destabilizing | None | N | 0.053 | neutral | N | 0.413716851 | None | None | I |
| I/M | 0.089 | likely_benign | 0.0795 | benign | -0.522 | Destabilizing | 0.171 | N | 0.359 | neutral | N | 0.477458398 | None | None | I |
| I/N | 0.2747 | likely_benign | 0.242 | benign | -0.618 | Destabilizing | 0.055 | N | 0.4 | neutral | N | 0.466733976 | None | None | I |
| I/P | 0.7796 | likely_pathogenic | 0.7286 | pathogenic | -0.897 | Destabilizing | 0.356 | N | 0.387 | neutral | None | None | None | None | I |
| I/Q | 0.3584 | ambiguous | 0.3217 | benign | -0.874 | Destabilizing | 0.356 | N | 0.349 | neutral | None | None | None | None | I |
| I/R | 0.226 | likely_benign | 0.1996 | benign | -0.224 | Destabilizing | 0.214 | N | 0.393 | neutral | None | None | None | None | I |
| I/S | 0.1833 | likely_benign | 0.1643 | benign | -1.141 | Destabilizing | 0.012 | N | 0.303 | neutral | N | 0.475034669 | None | None | I |
| I/T | 0.062 | likely_benign | 0.0583 | benign | -1.087 | Destabilizing | None | N | 0.143 | neutral | N | 0.427163364 | None | None | I |
| I/V | 0.0745 | likely_benign | 0.0746 | benign | -0.897 | Destabilizing | 0.002 | N | 0.18 | neutral | N | 0.509147242 | None | None | I |
| I/W | 0.648 | likely_pathogenic | 0.5907 | pathogenic | -1.037 | Destabilizing | 0.864 | D | 0.289 | neutral | None | None | None | None | I |
| I/Y | 0.4752 | ambiguous | 0.4066 | ambiguous | -0.84 | Destabilizing | 0.356 | N | 0.386 | 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.