Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14824 | 44695;44696;44697 | chr2:178625351;178625350;178625349 | chr2:179490078;179490077;179490076 |
| N2AB | 13183 | 39772;39773;39774 | chr2:178625351;178625350;178625349 | chr2:179490078;179490077;179490076 |
| N2A | 12256 | 36991;36992;36993 | chr2:178625351;178625350;178625349 | chr2:179490078;179490077;179490076 |
| N2B | 5759 | 17500;17501;17502 | chr2:178625351;178625350;178625349 | chr2:179490078;179490077;179490076 |
| Novex-1 | 5884 | 17875;17876;17877 | chr2:178625351;178625350;178625349 | chr2:179490078;179490077;179490076 |
| Novex-2 | 5951 | 18076;18077;18078 | chr2:178625351;178625350;178625349 | chr2:179490078;179490077;179490076 |
| 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/H | None | None | 0.994 | N | 0.737 | 0.236 | 0.251639045875 | gnomAD-4.0.0 | 6.90164E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.19136E-05 | 0 |
| D/N | rs781775537  |
-0.008 | 0.085 | N | 0.383 | 0.105 | 0.162503812791 | gnomAD-2.1.1 | 4.21E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.17E-06 | 0 |
| D/N | rs781775537 |
-0.008 | 0.085 | N | 0.383 | 0.105 | 0.162503812791 | gnomAD-4.0.0 | 1.38033E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.80731E-06 | 0 | 0 |
| D/V | rs1165288151 |
None | 0.989 | N | 0.757 | 0.494 | 0.409937222855 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/V | rs1165288151 |
None | 0.989 | N | 0.757 | 0.494 | 0.409937222855 | gnomAD-4.0.0 | 3.12266E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.25624E-06 | 0 | 0 |
| D/Y | None | None | 0.999 | D | 0.769 | 0.288 | 0.407082143382 | gnomAD-4.0.0 | 2.76066E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.61462E-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 | 0.3039 | likely_benign | 0.3376 | benign | -0.444 | Destabilizing | 0.978 | D | 0.687 | prob.neutral | N | 0.455001659 | None | None | N |
| D/C | 0.785 | likely_pathogenic | 0.8124 | pathogenic | 0.014 | Stabilizing | 0.999 | D | 0.762 | deleterious | None | None | None | None | N |
| D/E | 0.2645 | likely_benign | 0.2726 | benign | -0.395 | Destabilizing | 0.928 | D | 0.462 | neutral | N | 0.45386967 | None | None | N |
| D/F | 0.7461 | likely_pathogenic | 0.746 | pathogenic | -0.424 | Destabilizing | 0.999 | D | 0.773 | deleterious | None | None | None | None | N |
| D/G | 0.2007 | likely_benign | 0.2259 | benign | -0.671 | Destabilizing | 0.865 | D | 0.627 | neutral | N | 0.449990001 | None | None | N |
| D/H | 0.4292 | ambiguous | 0.4328 | ambiguous | -0.524 | Destabilizing | 0.994 | D | 0.737 | prob.delet. | N | 0.454147772 | None | None | N |
| D/I | 0.7074 | likely_pathogenic | 0.7288 | pathogenic | 0.115 | Stabilizing | 0.992 | D | 0.784 | deleterious | None | None | None | None | N |
| D/K | 0.5791 | likely_pathogenic | 0.6121 | pathogenic | 0.066 | Stabilizing | 0.968 | D | 0.705 | prob.neutral | None | None | None | None | N |
| D/L | 0.6391 | likely_pathogenic | 0.6555 | pathogenic | 0.115 | Stabilizing | 0.983 | D | 0.754 | deleterious | None | None | None | None | N |
| D/M | 0.8134 | likely_pathogenic | 0.8119 | pathogenic | 0.43 | Stabilizing | 0.999 | D | 0.762 | deleterious | None | None | None | None | N |
| D/N | 0.1004 | likely_benign | 0.1049 | benign | -0.177 | Destabilizing | 0.085 | N | 0.383 | neutral | N | 0.43464056 | None | None | N |
| D/P | 0.9129 | likely_pathogenic | 0.9135 | pathogenic | -0.049 | Destabilizing | 0.992 | D | 0.744 | deleterious | None | None | None | None | N |
| D/Q | 0.502 | ambiguous | 0.5301 | ambiguous | -0.145 | Destabilizing | 0.983 | D | 0.725 | prob.delet. | None | None | None | None | N |
| D/R | 0.6 | likely_pathogenic | 0.636 | pathogenic | 0.162 | Stabilizing | 0.983 | D | 0.75 | deleterious | None | None | None | None | N |
| D/S | 0.2063 | likely_benign | 0.2162 | benign | -0.33 | Destabilizing | 0.895 | D | 0.627 | neutral | None | None | None | None | N |
| D/T | 0.4868 | ambiguous | 0.5183 | ambiguous | -0.157 | Destabilizing | 0.983 | D | 0.707 | prob.neutral | None | None | None | None | N |
| D/V | 0.4912 | ambiguous | 0.5362 | ambiguous | -0.049 | Destabilizing | 0.989 | D | 0.757 | deleterious | N | 0.515472892 | None | None | N |
| D/W | 0.9309 | likely_pathogenic | 0.9302 | pathogenic | -0.3 | Destabilizing | 0.999 | D | 0.762 | deleterious | None | None | None | None | N |
| D/Y | 0.297 | likely_benign | 0.3143 | benign | -0.202 | Destabilizing | 0.999 | D | 0.769 | deleterious | D | 0.581106766 | 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.