Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14859 | 44800;44801;44802 | chr2:178624705;178624704;178624703 | chr2:179489432;179489431;179489430 |
| N2AB | 13218 | 39877;39878;39879 | chr2:178624705;178624704;178624703 | chr2:179489432;179489431;179489430 |
| N2A | 12291 | 37096;37097;37098 | chr2:178624705;178624704;178624703 | chr2:179489432;179489431;179489430 |
| N2B | 5794 | 17605;17606;17607 | chr2:178624705;178624704;178624703 | chr2:179489432;179489431;179489430 |
| Novex-1 | 5919 | 17980;17981;17982 | chr2:178624705;178624704;178624703 | chr2:179489432;179489431;179489430 |
| Novex-2 | 5986 | 18181;18182;18183 | chr2:178624705;178624704;178624703 | chr2:179489432;179489431;179489430 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/P | rs553230082  |
-1.714 | 1.0 | N | 0.907 | 0.594 | 0.789197078721 | gnomAD-2.1.1 | 2.83E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 2.28863E-04 | None | 0 | 0 | 0 |
| L/P | rs553230082 |
-1.714 | 1.0 | N | 0.907 | 0.594 | 0.789197078721 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 8.29187E-04 | 0 |
| L/P | rs553230082 |
-1.714 | 1.0 | N | 0.907 | 0.594 | 0.789197078721 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| L/P | rs553230082 |
-1.714 | 1.0 | N | 0.907 | 0.594 | 0.789197078721 | gnomAD-4.0.0 | 3.72171E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.79536E-06 | 3.35264E-04 | 5.69866E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9215 | likely_pathogenic | 0.9109 | pathogenic | -2.159 | Highly Destabilizing | 0.999 | D | 0.697 | prob.neutral | None | None | None | None | N |
| L/C | 0.9745 | likely_pathogenic | 0.9583 | pathogenic | -1.503 | Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | N |
| L/D | 0.9996 | likely_pathogenic | 0.9995 | pathogenic | -2.113 | Highly Destabilizing | 1.0 | D | 0.905 | deleterious | None | None | None | None | N |
| L/E | 0.9963 | likely_pathogenic | 0.9953 | pathogenic | -2.035 | Highly Destabilizing | 1.0 | D | 0.903 | deleterious | None | None | None | None | N |
| L/F | 0.9574 | likely_pathogenic | 0.9347 | pathogenic | -1.475 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | D | 0.668416097 | None | None | N |
| L/G | 0.9915 | likely_pathogenic | 0.9895 | pathogenic | -2.573 | Highly Destabilizing | 1.0 | D | 0.898 | deleterious | None | None | None | None | N |
| L/H | 0.9971 | likely_pathogenic | 0.9957 | pathogenic | -1.893 | Destabilizing | 1.0 | D | 0.889 | deleterious | D | 0.751278095 | None | None | N |
| L/I | 0.4922 | ambiguous | 0.4198 | ambiguous | -1.034 | Destabilizing | 0.999 | D | 0.506 | neutral | D | 0.545039717 | None | None | N |
| L/K | 0.9943 | likely_pathogenic | 0.9923 | pathogenic | -1.494 | Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | N |
| L/M | 0.6073 | likely_pathogenic | 0.4931 | ambiguous | -0.882 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| L/N | 0.9972 | likely_pathogenic | 0.9964 | pathogenic | -1.467 | Destabilizing | 1.0 | D | 0.907 | deleterious | None | None | None | None | N |
| L/P | 0.9807 | likely_pathogenic | 0.9667 | pathogenic | -1.382 | Destabilizing | 1.0 | D | 0.907 | deleterious | N | 0.506839445 | None | None | N |
| L/Q | 0.9905 | likely_pathogenic | 0.9856 | pathogenic | -1.579 | Destabilizing | 1.0 | D | 0.895 | deleterious | None | None | None | None | N |
| L/R | 0.9886 | likely_pathogenic | 0.9851 | pathogenic | -0.989 | Destabilizing | 1.0 | D | 0.89 | deleterious | D | 0.750048441 | None | None | N |
| L/S | 0.9932 | likely_pathogenic | 0.9897 | pathogenic | -2.128 | Highly Destabilizing | 1.0 | D | 0.868 | deleterious | None | None | None | None | N |
| L/T | 0.9695 | likely_pathogenic | 0.9525 | pathogenic | -1.926 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| L/V | 0.546 | ambiguous | 0.4345 | ambiguous | -1.382 | Destabilizing | 0.999 | D | 0.487 | neutral | D | 0.65915959 | None | None | N |
| L/W | 0.9961 | likely_pathogenic | 0.9931 | pathogenic | -1.676 | Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | N |
| L/Y | 0.9977 | likely_pathogenic | 0.9963 | pathogenic | -1.427 | Destabilizing | 1.0 | D | 0.864 | deleterious | 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.