Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14054 | 42385;42386;42387 | chr2:178634621;178634620;178634619 | chr2:179499348;179499347;179499346 |
| N2AB | 12413 | 37462;37463;37464 | chr2:178634621;178634620;178634619 | chr2:179499348;179499347;179499346 |
| N2A | 11486 | 34681;34682;34683 | chr2:178634621;178634620;178634619 | chr2:179499348;179499347;179499346 |
| N2B | 4989 | 15190;15191;15192 | chr2:178634621;178634620;178634619 | chr2:179499348;179499347;179499346 |
| Novex-1 | 5114 | 15565;15566;15567 | chr2:178634621;178634620;178634619 | chr2:179499348;179499347;179499346 |
| Novex-2 | 5181 | 15766;15767;15768 | chr2:178634621;178634620;178634619 | chr2:179499348;179499347;179499346 |
| 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 | rs1221996833  |
None | 0.989 | N | 0.456 | 0.312 | 0.520373764981 | 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 |
| L/F | rs1221996833 |
None | 0.989 | N | 0.456 | 0.312 | 0.520373764981 | gnomAD-4.0.0 | 6.5786E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47124E-05 | 0 | 0 |
| L/P | None | None | 0.998 | N | 0.633 | 0.476 | 0.795030053833 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-06 | 0 | 0 |
| L/R | None | None | 0.994 | N | 0.585 | 0.468 | 0.822958799421 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.7109 | likely_pathogenic | 0.7098 | pathogenic | -1.549 | Destabilizing | 0.97 | D | 0.435 | neutral | None | None | None | None | N |
| L/C | 0.9126 | likely_pathogenic | 0.9146 | pathogenic | -0.905 | Destabilizing | 1.0 | D | 0.509 | neutral | None | None | None | None | N |
| L/D | 0.9614 | likely_pathogenic | 0.9652 | pathogenic | -0.987 | Destabilizing | 0.999 | D | 0.638 | neutral | None | None | None | None | N |
| L/E | 0.8419 | likely_pathogenic | 0.8592 | pathogenic | -0.981 | Destabilizing | 0.999 | D | 0.643 | neutral | None | None | None | None | N |
| L/F | 0.6664 | likely_pathogenic | 0.6749 | pathogenic | -1.047 | Destabilizing | 0.989 | D | 0.456 | neutral | N | 0.499090591 | None | None | N |
| L/G | 0.9223 | likely_pathogenic | 0.9244 | pathogenic | -1.871 | Destabilizing | 0.996 | D | 0.645 | neutral | None | None | None | None | N |
| L/H | 0.8823 | likely_pathogenic | 0.8806 | pathogenic | -1.091 | Destabilizing | 1.0 | D | 0.666 | neutral | N | 0.501038157 | None | None | N |
| L/I | 0.231 | likely_benign | 0.2187 | benign | -0.739 | Destabilizing | 0.835 | D | 0.469 | neutral | N | 0.490376231 | None | None | N |
| L/K | 0.8082 | likely_pathogenic | 0.7991 | pathogenic | -1.133 | Destabilizing | 0.996 | D | 0.54 | neutral | None | None | None | None | N |
| L/M | 0.2357 | likely_benign | 0.2249 | benign | -0.615 | Destabilizing | 0.559 | D | 0.243 | neutral | None | None | None | None | N |
| L/N | 0.8704 | likely_pathogenic | 0.8604 | pathogenic | -0.919 | Destabilizing | 0.999 | D | 0.641 | neutral | None | None | None | None | N |
| L/P | 0.7324 | likely_pathogenic | 0.7318 | pathogenic | -0.978 | Destabilizing | 0.998 | D | 0.633 | neutral | N | 0.43276538 | None | None | N |
| L/Q | 0.7599 | likely_pathogenic | 0.7605 | pathogenic | -1.067 | Destabilizing | 0.996 | D | 0.578 | neutral | None | None | None | None | N |
| L/R | 0.7738 | likely_pathogenic | 0.7805 | pathogenic | -0.57 | Destabilizing | 0.994 | D | 0.585 | neutral | N | 0.500817258 | None | None | N |
| L/S | 0.8905 | likely_pathogenic | 0.8847 | pathogenic | -1.495 | Destabilizing | 0.996 | D | 0.5 | neutral | None | None | None | None | N |
| L/T | 0.6068 | likely_pathogenic | 0.5747 | pathogenic | -1.369 | Destabilizing | 0.97 | D | 0.4 | neutral | None | None | None | None | N |
| L/V | 0.2466 | likely_benign | 0.2286 | benign | -0.978 | Destabilizing | 0.248 | N | 0.213 | neutral | N | 0.476962805 | None | None | N |
| L/W | 0.772 | likely_pathogenic | 0.7957 | pathogenic | -1.126 | Destabilizing | 1.0 | D | 0.64 | neutral | None | None | None | None | N |
| L/Y | 0.8728 | likely_pathogenic | 0.8768 | pathogenic | -0.911 | Destabilizing | 0.999 | D | 0.467 | neutral | 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.