Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35177 | 105754;105755;105756 | chr2:178531086;178531085;178531084 | chr2:179395813;179395812;179395811 |
| N2AB | 33536 | 100831;100832;100833 | chr2:178531086;178531085;178531084 | chr2:179395813;179395812;179395811 |
| N2A | 32609 | 98050;98051;98052 | chr2:178531086;178531085;178531084 | chr2:179395813;179395812;179395811 |
| N2B | 26112 | 78559;78560;78561 | chr2:178531086;178531085;178531084 | chr2:179395813;179395812;179395811 |
| Novex-1 | 26237 | 78934;78935;78936 | chr2:178531086;178531085;178531084 | chr2:179395813;179395812;179395811 |
| Novex-2 | 26304 | 79135;79136;79137 | chr2:178531086;178531085;178531084 | chr2:179395813;179395812;179395811 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/M | rs55865284  |
-0.711 | 0.624 | D | 0.486 | 0.153 | None | gnomAD-2.1.1 | 3.28591E-03 | None | None | None | None | N | None | 3.45982E-02 | 1.7526E-03 | None | 0 | 0 | None | 0 | None | 0 | 7.79E-05 | 1.82124E-03 |
| V/M | rs55865284 |
-0.711 | 0.624 | D | 0.486 | 0.153 | None | gnomAD-3.1.2 | 1.00823E-02 | None | None | None | None | N | None | 3.43246E-02 | 5.10739E-03 | 0 | 0 | 0 | None | 0 | 6.32911E-03 | 1.47007E-04 | 0 | 1.05062E-02 |
| V/M | rs55865284 |
-0.711 | 0.624 | D | 0.486 | 0.153 | None | 1000 genomes | 1.05831E-02 | None | None | None | None | N | None | 3.78E-02 | 4.3E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| V/M | rs55865284 |
-0.711 | 0.624 | D | 0.486 | 0.153 | None | gnomAD-4.0.0 | 1.88666E-03 | None | None | None | None | N | None | 3.46137E-02 | 2.866E-03 | None | 0 | 0 | None | 0 | 1.81458E-03 | 7.45841E-05 | 4.39174E-05 | 2.76844E-03 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.4399 | ambiguous | 0.4216 | ambiguous | -1.536 | Destabilizing | 0.164 | N | 0.403 | neutral | N | 0.51614821 | None | None | N |
| V/C | 0.9151 | likely_pathogenic | 0.914 | pathogenic | -1.233 | Destabilizing | 0.981 | D | 0.509 | neutral | None | None | None | None | N |
| V/D | 0.7848 | likely_pathogenic | 0.7455 | pathogenic | -1.085 | Destabilizing | 0.932 | D | 0.626 | neutral | None | None | None | None | N |
| V/E | 0.5401 | ambiguous | 0.5136 | ambiguous | -1.068 | Destabilizing | 0.771 | D | 0.572 | neutral | N | 0.509782336 | None | None | N |
| V/F | 0.3186 | likely_benign | 0.3008 | benign | -1.283 | Destabilizing | 0.688 | D | 0.511 | neutral | None | None | None | None | N |
| V/G | 0.497 | ambiguous | 0.4655 | ambiguous | -1.874 | Destabilizing | 0.771 | D | 0.615 | neutral | N | 0.511339272 | None | None | N |
| V/H | 0.8536 | likely_pathogenic | 0.8351 | pathogenic | -1.42 | Destabilizing | 0.981 | D | 0.645 | neutral | None | None | None | None | N |
| V/I | 0.0948 | likely_benign | 0.0938 | benign | -0.7 | Destabilizing | 0.001 | N | 0.112 | neutral | None | None | None | None | N |
| V/K | 0.6435 | likely_pathogenic | 0.6082 | pathogenic | -1.053 | Destabilizing | 0.817 | D | 0.578 | neutral | None | None | None | None | N |
| V/L | 0.3635 | ambiguous | 0.3492 | ambiguous | -0.7 | Destabilizing | 0.001 | N | 0.107 | neutral | N | 0.498525683 | None | None | N |
| V/M | 0.2355 | likely_benign | 0.2721 | benign | -0.619 | Destabilizing | 0.624 | D | 0.486 | neutral | D | 0.531715537 | None | None | N |
| V/N | 0.6743 | likely_pathogenic | 0.6286 | pathogenic | -0.88 | Destabilizing | 0.932 | D | 0.634 | neutral | None | None | None | None | N |
| V/P | 0.9116 | likely_pathogenic | 0.8793 | pathogenic | -0.944 | Destabilizing | 0.932 | D | 0.59 | neutral | None | None | None | None | N |
| V/Q | 0.6027 | likely_pathogenic | 0.5767 | pathogenic | -1.028 | Destabilizing | 0.932 | D | 0.593 | neutral | None | None | None | None | N |
| V/R | 0.6245 | likely_pathogenic | 0.5904 | pathogenic | -0.636 | Destabilizing | 0.817 | D | 0.635 | neutral | None | None | None | None | N |
| V/S | 0.5954 | likely_pathogenic | 0.5608 | ambiguous | -1.512 | Destabilizing | 0.817 | D | 0.562 | neutral | None | None | None | None | N |
| V/T | 0.4787 | ambiguous | 0.4491 | ambiguous | -1.369 | Destabilizing | 0.386 | N | 0.445 | neutral | None | None | None | None | N |
| V/W | 0.9252 | likely_pathogenic | 0.92 | pathogenic | -1.436 | Destabilizing | 0.981 | D | 0.678 | prob.neutral | None | None | None | None | N |
| V/Y | 0.7714 | likely_pathogenic | 0.752 | pathogenic | -1.12 | Destabilizing | 0.817 | D | 0.52 | 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.