Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19446 | 58561;58562;58563 | chr2:178594057;178594056;178594055 | chr2:179458784;179458783;179458782 |
| N2AB | 17805 | 53638;53639;53640 | chr2:178594057;178594056;178594055 | chr2:179458784;179458783;179458782 |
| N2A | 16878 | 50857;50858;50859 | chr2:178594057;178594056;178594055 | chr2:179458784;179458783;179458782 |
| N2B | 10381 | 31366;31367;31368 | chr2:178594057;178594056;178594055 | chr2:179458784;179458783;179458782 |
| Novex-1 | 10506 | 31741;31742;31743 | chr2:178594057;178594056;178594055 | chr2:179458784;179458783;179458782 |
| Novex-2 | 10573 | 31942;31943;31944 | chr2:178594057;178594056;178594055 | chr2:179458784;179458783;179458782 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/E | None | None | 0.425 | N | 0.477 | 0.204 | 0.39709148275 | 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 |
| K/N | rs536286313  |
-1.036 | 0.01 | N | 0.271 | 0.137 | 0.162503812791 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| K/N | rs536286313 |
-1.036 | 0.01 | N | 0.271 | 0.137 | 0.162503812791 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| K/N | rs536286313 |
-1.036 | 0.01 | N | 0.271 | 0.137 | 0.162503812791 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| K/N | rs536286313 |
-1.036 | 0.01 | N | 0.271 | 0.137 | 0.162503812791 | gnomAD-4.0.0 | 6.57022E-06 | None | None | None | None | N | None | 2.40616E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.5642 | likely_pathogenic | 0.4931 | ambiguous | -1.221 | Destabilizing | 0.495 | N | 0.452 | neutral | None | None | None | None | N |
| K/C | 0.5583 | ambiguous | 0.5059 | ambiguous | -1.477 | Destabilizing | 0.995 | D | 0.698 | prob.neutral | None | None | None | None | N |
| K/D | 0.8957 | likely_pathogenic | 0.8595 | pathogenic | -1.764 | Destabilizing | 0.543 | D | 0.515 | neutral | None | None | None | None | N |
| K/E | 0.527 | ambiguous | 0.4257 | ambiguous | -1.502 | Destabilizing | 0.425 | N | 0.477 | neutral | N | 0.478531626 | None | None | N |
| K/F | 0.8264 | likely_pathogenic | 0.7637 | pathogenic | -0.55 | Destabilizing | 0.893 | D | 0.683 | prob.neutral | None | None | None | None | N |
| K/G | 0.7587 | likely_pathogenic | 0.6953 | pathogenic | -1.689 | Destabilizing | 0.495 | N | 0.581 | neutral | None | None | None | None | N |
| K/H | 0.4568 | ambiguous | 0.4096 | ambiguous | -1.941 | Destabilizing | 0.944 | D | 0.584 | neutral | None | None | None | None | N |
| K/I | 0.1369 | likely_benign | 0.0911 | benign | 0.084 | Stabilizing | 0.001 | N | 0.413 | neutral | None | None | None | None | N |
| K/L | 0.365 | ambiguous | 0.2676 | benign | 0.084 | Stabilizing | 0.176 | N | 0.462 | neutral | None | None | None | None | N |
| K/M | 0.1895 | likely_benign | 0.1344 | benign | -0.221 | Destabilizing | 0.863 | D | 0.589 | neutral | N | 0.424793142 | None | None | N |
| K/N | 0.5583 | ambiguous | 0.4854 | ambiguous | -1.729 | Destabilizing | 0.01 | N | 0.271 | neutral | N | 0.398166688 | None | None | N |
| K/P | 0.9608 | likely_pathogenic | 0.9348 | pathogenic | -0.327 | Destabilizing | 0.981 | D | 0.581 | neutral | None | None | None | None | N |
| K/Q | 0.2926 | likely_benign | 0.2407 | benign | -1.433 | Destabilizing | 0.784 | D | 0.491 | neutral | N | 0.459945865 | None | None | N |
| K/R | 0.1325 | likely_benign | 0.1209 | benign | -1.23 | Destabilizing | 0.784 | D | 0.479 | neutral | N | 0.478531626 | None | None | N |
| K/S | 0.7334 | likely_pathogenic | 0.6563 | pathogenic | -2.226 | Highly Destabilizing | 0.495 | N | 0.489 | neutral | None | None | None | None | N |
| K/T | 0.2533 | likely_benign | 0.1983 | benign | -1.714 | Destabilizing | 0.425 | N | 0.493 | neutral | N | 0.448728794 | None | None | N |
| K/V | 0.1451 | likely_benign | 0.1177 | benign | -0.327 | Destabilizing | 0.176 | N | 0.466 | neutral | None | None | None | None | N |
| K/W | 0.9018 | likely_pathogenic | 0.865 | pathogenic | -0.663 | Destabilizing | 0.995 | D | 0.695 | prob.neutral | None | None | None | None | N |
| K/Y | 0.6848 | likely_pathogenic | 0.6081 | pathogenic | -0.275 | Destabilizing | 0.981 | D | 0.661 | 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.