Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35003 | 105232;105233;105234 | chr2:178531608;178531607;178531606 | chr2:179396335;179396334;179396333 |
| N2AB | 33362 | 100309;100310;100311 | chr2:178531608;178531607;178531606 | chr2:179396335;179396334;179396333 |
| N2A | 32435 | 97528;97529;97530 | chr2:178531608;178531607;178531606 | chr2:179396335;179396334;179396333 |
| N2B | 25938 | 78037;78038;78039 | chr2:178531608;178531607;178531606 | chr2:179396335;179396334;179396333 |
| Novex-1 | 26063 | 78412;78413;78414 | chr2:178531608;178531607;178531606 | chr2:179396335;179396334;179396333 |
| Novex-2 | 26130 | 78613;78614;78615 | chr2:178531608;178531607;178531606 | chr2:179396335;179396334;179396333 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | None | None | 1.0 | N | 0.761 | 0.516 | 0.317084106153 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 6.07533E-05 | 0 |
| D/N | None | None | 1.0 | N | 0.635 | 0.3 | 0.185906805712 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| D/Y | None | None | 1.0 | N | 0.767 | 0.326 | 0.377097596864 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.4222 | ambiguous | 0.4506 | ambiguous | -0.295 | Destabilizing | 1.0 | D | 0.761 | deleterious | N | 0.477970613 | None | None | N |
| D/C | 0.8803 | likely_pathogenic | 0.8997 | pathogenic | 0.014 | Stabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| D/E | 0.3855 | ambiguous | 0.4203 | ambiguous | -0.532 | Destabilizing | 1.0 | D | 0.425 | neutral | N | 0.408956032 | None | None | N |
| D/F | 0.903 | likely_pathogenic | 0.9064 | pathogenic | -0.41 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | N |
| D/G | 0.2623 | likely_benign | 0.3091 | benign | -0.552 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | N | 0.461019648 | None | None | N |
| D/H | 0.5417 | ambiguous | 0.586 | pathogenic | -0.768 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | N | 0.483339147 | None | None | N |
| D/I | 0.9349 | likely_pathogenic | 0.934 | pathogenic | 0.35 | Stabilizing | 1.0 | D | 0.796 | deleterious | None | None | None | None | N |
| D/K | 0.7676 | likely_pathogenic | 0.8034 | pathogenic | -0.3 | Destabilizing | 1.0 | D | 0.746 | deleterious | None | None | None | None | N |
| D/L | 0.8167 | likely_pathogenic | 0.8326 | pathogenic | 0.35 | Stabilizing | 1.0 | D | 0.81 | deleterious | None | None | None | None | N |
| D/M | 0.9454 | likely_pathogenic | 0.9472 | pathogenic | 0.775 | Stabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | N |
| D/N | 0.1294 | likely_benign | 0.1376 | benign | -0.438 | Destabilizing | 1.0 | D | 0.635 | neutral | N | 0.399909687 | None | None | N |
| D/P | 0.9642 | likely_pathogenic | 0.9737 | pathogenic | 0.159 | Stabilizing | 1.0 | D | 0.738 | prob.delet. | None | None | None | None | N |
| D/Q | 0.617 | likely_pathogenic | 0.6665 | pathogenic | -0.359 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | N |
| D/R | 0.7195 | likely_pathogenic | 0.7606 | pathogenic | -0.265 | Destabilizing | 1.0 | D | 0.806 | deleterious | None | None | None | None | N |
| D/S | 0.2366 | likely_benign | 0.2501 | benign | -0.622 | Destabilizing | 1.0 | D | 0.68 | prob.neutral | None | None | None | None | N |
| D/T | 0.712 | likely_pathogenic | 0.7303 | pathogenic | -0.432 | Destabilizing | 1.0 | D | 0.748 | deleterious | None | None | None | None | N |
| D/V | 0.8306 | likely_pathogenic | 0.8275 | pathogenic | 0.159 | Stabilizing | 1.0 | D | 0.804 | deleterious | N | 0.460455508 | None | None | N |
| D/W | 0.9775 | likely_pathogenic | 0.9807 | pathogenic | -0.416 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| D/Y | 0.5617 | ambiguous | 0.5683 | pathogenic | -0.249 | Destabilizing | 1.0 | D | 0.767 | deleterious | N | 0.486206094 | 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.