Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30588 | 91987;91988;91989 | chr2:178550076;178550075;178550074 | chr2:179414803;179414802;179414801 |
| N2AB | 28947 | 87064;87065;87066 | chr2:178550076;178550075;178550074 | chr2:179414803;179414802;179414801 |
| N2A | 28020 | 84283;84284;84285 | chr2:178550076;178550075;178550074 | chr2:179414803;179414802;179414801 |
| N2B | 21523 | 64792;64793;64794 | chr2:178550076;178550075;178550074 | chr2:179414803;179414802;179414801 |
| Novex-1 | 21648 | 65167;65168;65169 | chr2:178550076;178550075;178550074 | chr2:179414803;179414802;179414801 |
| Novex-2 | 21715 | 65368;65369;65370 | chr2:178550076;178550075;178550074 | chr2:179414803;179414802;179414801 |
| 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 | 0.946 | N | 0.645 | 0.314 | 0.315903272564 | gnomAD-4.0.0 | 6.84216E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99484E-07 | 0 | 0 |
| D/G | rs756837722  |
-0.012 | 0.834 | N | 0.646 | 0.318 | 0.170165803431 | gnomAD-2.1.1 | 7.14E-06 | None | None | None | None | N | None | 4.13E-05 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| D/G | rs756837722 |
-0.012 | 0.834 | N | 0.646 | 0.318 | 0.170165803431 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07383E-04 | 0 |
| D/G | rs756837722 |
-0.012 | 0.834 | N | 0.646 | 0.318 | 0.170165803431 | gnomAD-4.0.0 | 3.0985E-06 | None | None | None | None | N | None | 1.33483E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 4.39203E-05 | 0 |
| D/H | rs878854399 |
-0.236 | 0.077 | N | 0.421 | 0.141 | 0.124217242631 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/H | rs878854399 |
-0.236 | 0.077 | N | 0.421 | 0.141 | 0.124217242631 | gnomAD-4.0.0 | 3.18262E-06 | None | None | None | None | N | None | 0 | 2.28645E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02444E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.4356 | ambiguous | 0.5116 | ambiguous | -0.041 | Destabilizing | 0.946 | D | 0.645 | neutral | N | 0.489014326 | None | None | N |
| D/C | 0.8181 | likely_pathogenic | 0.8591 | pathogenic | 0.41 | Stabilizing | 0.998 | D | 0.748 | deleterious | None | None | None | None | N |
| D/E | 0.2638 | likely_benign | 0.3133 | benign | -0.203 | Destabilizing | 0.716 | D | 0.411 | neutral | N | 0.438316146 | None | None | N |
| D/F | 0.7182 | likely_pathogenic | 0.7777 | pathogenic | -0.328 | Destabilizing | 0.959 | D | 0.745 | deleterious | None | None | None | None | N |
| D/G | 0.36 | ambiguous | 0.4172 | ambiguous | -0.207 | Destabilizing | 0.834 | D | 0.646 | neutral | N | 0.491995916 | None | None | N |
| D/H | 0.5459 | ambiguous | 0.6362 | pathogenic | -0.353 | Destabilizing | 0.077 | N | 0.421 | neutral | N | 0.505965291 | None | None | N |
| D/I | 0.7185 | likely_pathogenic | 0.7801 | pathogenic | 0.334 | Stabilizing | 0.979 | D | 0.747 | deleterious | None | None | None | None | N |
| D/K | 0.7456 | likely_pathogenic | 0.8006 | pathogenic | 0.475 | Stabilizing | 0.959 | D | 0.721 | prob.delet. | None | None | None | None | N |
| D/L | 0.6571 | likely_pathogenic | 0.7301 | pathogenic | 0.334 | Stabilizing | 0.959 | D | 0.723 | prob.delet. | None | None | None | None | N |
| D/M | 0.8049 | likely_pathogenic | 0.8528 | pathogenic | 0.597 | Stabilizing | 0.998 | D | 0.729 | prob.delet. | None | None | None | None | N |
| D/N | 0.2234 | likely_benign | 0.2604 | benign | 0.414 | Stabilizing | 0.716 | D | 0.649 | neutral | N | 0.387788539 | None | None | N |
| D/P | 0.9513 | likely_pathogenic | 0.9681 | pathogenic | 0.231 | Stabilizing | 0.979 | D | 0.713 | prob.delet. | None | None | None | None | N |
| D/Q | 0.6363 | likely_pathogenic | 0.6974 | pathogenic | 0.408 | Stabilizing | 0.959 | D | 0.698 | prob.neutral | None | None | None | None | N |
| D/R | 0.7494 | likely_pathogenic | 0.7954 | pathogenic | 0.446 | Stabilizing | 0.959 | D | 0.71 | prob.delet. | None | None | None | None | N |
| D/S | 0.3412 | ambiguous | 0.4032 | ambiguous | 0.285 | Stabilizing | 0.87 | D | 0.658 | neutral | None | None | None | None | N |
| D/T | 0.5832 | likely_pathogenic | 0.6471 | pathogenic | 0.402 | Stabilizing | 0.979 | D | 0.727 | prob.delet. | None | None | None | None | N |
| D/V | 0.5152 | ambiguous | 0.5842 | pathogenic | 0.231 | Stabilizing | 0.973 | D | 0.723 | prob.delet. | N | 0.506312007 | None | None | N |
| D/W | 0.924 | likely_pathogenic | 0.94 | pathogenic | -0.34 | Destabilizing | 0.998 | D | 0.755 | deleterious | None | None | None | None | N |
| D/Y | 0.3243 | likely_benign | 0.3689 | ambiguous | -0.121 | Destabilizing | 0.898 | D | 0.749 | deleterious | N | 0.457733257 | 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.