Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24519 | 73780;73781;73782 | chr2:178572577;178572576;178572575 | chr2:179437304;179437303;179437302 |
| N2AB | 22878 | 68857;68858;68859 | chr2:178572577;178572576;178572575 | chr2:179437304;179437303;179437302 |
| N2A | 21951 | 66076;66077;66078 | chr2:178572577;178572576;178572575 | chr2:179437304;179437303;179437302 |
| N2B | 15454 | 46585;46586;46587 | chr2:178572577;178572576;178572575 | chr2:179437304;179437303;179437302 |
| Novex-1 | 15579 | 46960;46961;46962 | chr2:178572577;178572576;178572575 | chr2:179437304;179437303;179437302 |
| Novex-2 | 15646 | 47161;47162;47163 | chr2:178572577;178572576;178572575 | chr2:179437304;179437303;179437302 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs747442288  |
-0.408 | 0.977 | N | 0.585 | 0.293 | 0.293502639404 | gnomAD-2.1.1 | 7.15E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.15E-05 | None | 3.27E-05 | None | 0 | 0 | 0 |
| T/I | rs747442288 |
-0.408 | 0.977 | N | 0.585 | 0.293 | 0.293502639404 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 1.93798E-04 | None | 0 | 0 | 0 | 0 | 0 |
| T/I | rs747442288 |
-0.408 | 0.977 | N | 0.585 | 0.293 | 0.293502639404 | gnomAD-4.0.0 | 5.57862E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.23344E-05 | None | 0 | 0 | 5.08641E-06 | 2.19626E-05 | 0 |
| T/P | None | None | 0.9 | N | 0.583 | 0.247 | 0.267299060538 | gnomAD-4.0.0 | 1.592E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43303E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.3383 | likely_benign | 0.2574 | benign | -0.94 | Destabilizing | 0.078 | N | 0.412 | neutral | N | 0.493627925 | None | None | I |
| T/C | 0.8142 | likely_pathogenic | 0.7599 | pathogenic | -0.553 | Destabilizing | 0.998 | D | 0.583 | neutral | None | None | None | None | I |
| T/D | 0.9639 | likely_pathogenic | 0.9408 | pathogenic | -0.008 | Destabilizing | 0.854 | D | 0.525 | neutral | None | None | None | None | I |
| T/E | 0.9355 | likely_pathogenic | 0.8942 | pathogenic | -0.053 | Destabilizing | 0.848 | D | 0.637 | neutral | None | None | None | None | I |
| T/F | 0.9111 | likely_pathogenic | 0.8492 | pathogenic | -1.299 | Destabilizing | 0.998 | D | 0.815 | deleterious | None | None | None | None | I |
| T/G | 0.737 | likely_pathogenic | 0.6818 | pathogenic | -1.109 | Destabilizing | 0.933 | D | 0.602 | neutral | None | None | None | None | I |
| T/H | 0.8539 | likely_pathogenic | 0.7964 | pathogenic | -1.438 | Destabilizing | 0.995 | D | 0.78 | deleterious | None | None | None | None | I |
| T/I | 0.7929 | likely_pathogenic | 0.6804 | pathogenic | -0.593 | Destabilizing | 0.977 | D | 0.585 | neutral | N | 0.501575404 | None | None | I |
| T/K | 0.8667 | likely_pathogenic | 0.7725 | pathogenic | -0.547 | Destabilizing | 0.746 | D | 0.641 | neutral | N | 0.448836997 | None | None | I |
| T/L | 0.5817 | likely_pathogenic | 0.4721 | ambiguous | -0.593 | Destabilizing | 0.886 | D | 0.65 | prob.neutral | None | None | None | None | I |
| T/M | 0.4219 | ambiguous | 0.3204 | benign | -0.148 | Destabilizing | 0.998 | D | 0.542 | neutral | None | None | None | None | I |
| T/N | 0.6552 | likely_pathogenic | 0.5392 | ambiguous | -0.37 | Destabilizing | 0.854 | D | 0.541 | neutral | None | None | None | None | I |
| T/P | 0.5931 | likely_pathogenic | 0.5208 | ambiguous | -0.681 | Destabilizing | 0.9 | D | 0.583 | neutral | N | 0.461744793 | None | None | I |
| T/Q | 0.8314 | likely_pathogenic | 0.7553 | pathogenic | -0.681 | Destabilizing | 0.927 | D | 0.595 | neutral | None | None | None | None | I |
| T/R | 0.8458 | likely_pathogenic | 0.7615 | pathogenic | -0.262 | Destabilizing | 0.102 | N | 0.347 | neutral | N | 0.452589379 | None | None | I |
| T/S | 0.1979 | likely_benign | 0.175 | benign | -0.706 | Destabilizing | 0.016 | N | 0.245 | neutral | N | 0.455592398 | None | None | I |
| T/V | 0.5669 | likely_pathogenic | 0.4612 | ambiguous | -0.681 | Destabilizing | 0.919 | D | 0.593 | neutral | None | None | None | None | I |
| T/W | 0.9839 | likely_pathogenic | 0.9732 | pathogenic | -1.151 | Destabilizing | 0.999 | D | 0.815 | deleterious | None | None | None | None | I |
| T/Y | 0.8951 | likely_pathogenic | 0.8418 | pathogenic | -0.925 | Destabilizing | 0.998 | D | 0.813 | deleterious | None | None | None | None | I |
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.