Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26036 | 78331;78332;78333 | chr2:178568026;178568025;178568024 | chr2:179432753;179432752;179432751 |
| N2AB | 24395 | 73408;73409;73410 | chr2:178568026;178568025;178568024 | chr2:179432753;179432752;179432751 |
| N2A | 23468 | 70627;70628;70629 | chr2:178568026;178568025;178568024 | chr2:179432753;179432752;179432751 |
| N2B | 16971 | 51136;51137;51138 | chr2:178568026;178568025;178568024 | chr2:179432753;179432752;179432751 |
| Novex-1 | 17096 | 51511;51512;51513 | chr2:178568026;178568025;178568024 | chr2:179432753;179432752;179432751 |
| Novex-2 | 17163 | 51712;51713;51714 | chr2:178568026;178568025;178568024 | chr2:179432753;179432752;179432751 |
| 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/F | rs904868866  |
-0.636 | 0.967 | N | 0.468 | 0.248 | 0.454798141022 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.94E-06 | 0 |
| L/F | rs904868866 |
-0.636 | 0.967 | N | 0.468 | 0.248 | 0.454798141022 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| L/F | rs904868866 |
-0.636 | 0.967 | N | 0.468 | 0.248 | 0.454798141022 | gnomAD-4.0.0 | 2.05312E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.6988E-06 | 0 | 0 |
| L/S | None | None | 0.967 | N | 0.549 | 0.452 | 0.768949010136 | gnomAD-4.0.0 | 1.59218E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43291E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.8484 | likely_pathogenic | 0.8893 | pathogenic | -0.724 | Destabilizing | 0.916 | D | 0.502 | neutral | None | None | None | None | I |
| L/C | 0.9054 | likely_pathogenic | 0.9278 | pathogenic | -0.663 | Destabilizing | 0.999 | D | 0.545 | neutral | None | None | None | None | I |
| L/D | 0.9924 | likely_pathogenic | 0.9942 | pathogenic | -0.111 | Destabilizing | 0.987 | D | 0.646 | neutral | None | None | None | None | I |
| L/E | 0.9613 | likely_pathogenic | 0.9725 | pathogenic | -0.173 | Destabilizing | 0.975 | D | 0.647 | neutral | None | None | None | None | I |
| L/F | 0.5189 | ambiguous | 0.6322 | pathogenic | -0.592 | Destabilizing | 0.967 | D | 0.468 | neutral | N | 0.486688336 | None | None | I |
| L/G | 0.9624 | likely_pathogenic | 0.9703 | pathogenic | -0.908 | Destabilizing | 0.975 | D | 0.647 | neutral | None | None | None | None | I |
| L/H | 0.8288 | likely_pathogenic | 0.8619 | pathogenic | -0.053 | Destabilizing | 0.997 | D | 0.629 | neutral | None | None | None | None | I |
| L/I | 0.2016 | likely_benign | 0.2686 | benign | -0.347 | Destabilizing | 0.845 | D | 0.465 | neutral | None | None | None | None | I |
| L/K | 0.8855 | likely_pathogenic | 0.9076 | pathogenic | -0.39 | Destabilizing | 0.95 | D | 0.487 | neutral | None | None | None | None | I |
| L/M | 0.2312 | likely_benign | 0.3383 | benign | -0.507 | Destabilizing | 0.63 | D | 0.435 | neutral | N | 0.472369516 | None | None | I |
| L/N | 0.9172 | likely_pathogenic | 0.937 | pathogenic | -0.266 | Destabilizing | 0.975 | D | 0.636 | neutral | None | None | None | None | I |
| L/P | 0.9821 | likely_pathogenic | 0.9852 | pathogenic | -0.44 | Destabilizing | 0.996 | D | 0.646 | neutral | None | None | None | None | I |
| L/Q | 0.7522 | likely_pathogenic | 0.8282 | pathogenic | -0.437 | Destabilizing | 0.975 | D | 0.561 | neutral | None | None | None | None | I |
| L/R | 0.7929 | likely_pathogenic | 0.8108 | pathogenic | 0.145 | Stabilizing | 0.073 | N | 0.512 | neutral | None | None | None | None | I |
| L/S | 0.9018 | likely_pathogenic | 0.9365 | pathogenic | -0.748 | Destabilizing | 0.967 | D | 0.549 | neutral | N | 0.508280451 | None | None | I |
| L/T | 0.8125 | likely_pathogenic | 0.8639 | pathogenic | -0.698 | Destabilizing | 0.975 | D | 0.495 | neutral | None | None | None | None | I |
| L/V | 0.3062 | likely_benign | 0.3985 | ambiguous | -0.44 | Destabilizing | 0.805 | D | 0.496 | neutral | N | 0.519326951 | None | None | I |
| L/W | 0.8031 | likely_pathogenic | 0.8534 | pathogenic | -0.613 | Destabilizing | 0.999 | D | 0.633 | neutral | N | 0.490055697 | None | None | I |
| L/Y | 0.8328 | likely_pathogenic | 0.8765 | pathogenic | -0.38 | Destabilizing | 0.987 | D | 0.51 | neutral | 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.