Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15263 | 46012;46013;46014 | chr2:178620823;178620822;178620821 | chr2:179485550;179485549;179485548 |
| N2AB | 13622 | 41089;41090;41091 | chr2:178620823;178620822;178620821 | chr2:179485550;179485549;179485548 |
| N2A | 12695 | 38308;38309;38310 | chr2:178620823;178620822;178620821 | chr2:179485550;179485549;179485548 |
| N2B | 6198 | 18817;18818;18819 | chr2:178620823;178620822;178620821 | chr2:179485550;179485549;179485548 |
| Novex-1 | 6323 | 19192;19193;19194 | chr2:178620823;178620822;178620821 | chr2:179485550;179485549;179485548 |
| Novex-2 | 6390 | 19393;19394;19395 | chr2:178620823;178620822;178620821 | chr2:179485550;179485549;179485548 |
| 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/N | rs1198734931  |
-1.429 | 0.338 | N | 0.588 | 0.351 | 0.42130639912 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.49E-05 | 0 |
| T/N | rs1198734931 |
-1.429 | 0.338 | N | 0.588 | 0.351 | 0.42130639912 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| T/N | rs1198734931 |
-1.429 | 0.338 | N | 0.588 | 0.351 | 0.42130639912 | gnomAD-4.0.0 | 3.10064E-06 | None | None | None | None | N | None | 1.33722E-05 | 0 | None | 0 | 2.23404E-05 | None | 0 | 0 | 1.69612E-06 | 0 | 1.60282E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1569 | likely_benign | 0.1869 | benign | -1.108 | Destabilizing | 0.174 | N | 0.469 | neutral | D | 0.538402457 | None | None | N |
| T/C | 0.6528 | likely_pathogenic | 0.6591 | pathogenic | -0.837 | Destabilizing | 0.973 | D | 0.708 | prob.delet. | None | None | None | None | N |
| T/D | 0.8577 | likely_pathogenic | 0.8819 | pathogenic | -1.88 | Destabilizing | 0.575 | D | 0.619 | neutral | None | None | None | None | N |
| T/E | 0.6662 | likely_pathogenic | 0.7118 | pathogenic | -1.622 | Destabilizing | 0.404 | N | 0.619 | neutral | None | None | None | None | N |
| T/F | 0.6053 | likely_pathogenic | 0.6417 | pathogenic | -0.618 | Destabilizing | 0.906 | D | 0.74 | deleterious | None | None | None | None | N |
| T/G | 0.5776 | likely_pathogenic | 0.6208 | pathogenic | -1.554 | Destabilizing | 0.404 | N | 0.618 | neutral | None | None | None | None | N |
| T/H | 0.503 | ambiguous | 0.5515 | ambiguous | -1.613 | Destabilizing | 0.973 | D | 0.731 | prob.delet. | None | None | None | None | N |
| T/I | 0.3953 | ambiguous | 0.4188 | ambiguous | 0.087 | Stabilizing | 0.782 | D | 0.671 | neutral | D | 0.522943191 | None | None | N |
| T/K | 0.561 | ambiguous | 0.6187 | pathogenic | -0.567 | Destabilizing | 0.404 | N | 0.617 | neutral | None | None | None | None | N |
| T/L | 0.2878 | likely_benign | 0.3027 | benign | 0.087 | Stabilizing | 0.575 | D | 0.595 | neutral | None | None | None | None | N |
| T/M | 0.1639 | likely_benign | 0.1757 | benign | -0.164 | Destabilizing | 0.991 | D | 0.715 | prob.delet. | None | None | None | None | N |
| T/N | 0.3354 | likely_benign | 0.3967 | ambiguous | -1.473 | Destabilizing | 0.338 | N | 0.588 | neutral | N | 0.521892555 | None | None | N |
| T/P | 0.8566 | likely_pathogenic | 0.8672 | pathogenic | -0.282 | Destabilizing | 0.782 | D | 0.67 | neutral | D | 0.607250664 | None | None | N |
| T/Q | 0.4296 | ambiguous | 0.4865 | ambiguous | -1.068 | Destabilizing | 0.826 | D | 0.709 | prob.delet. | None | None | None | None | N |
| T/R | 0.4466 | ambiguous | 0.4912 | ambiguous | -0.946 | Destabilizing | 0.826 | D | 0.699 | prob.neutral | None | None | None | None | N |
| T/S | 0.1568 | likely_benign | 0.192 | benign | -1.616 | Destabilizing | 0.001 | N | 0.266 | neutral | N | 0.44464574 | None | None | N |
| T/V | 0.308 | likely_benign | 0.3211 | benign | -0.282 | Destabilizing | 0.575 | D | 0.566 | neutral | None | None | None | None | N |
| T/W | 0.8802 | likely_pathogenic | 0.895 | pathogenic | -0.933 | Destabilizing | 0.991 | D | 0.728 | prob.delet. | None | None | None | None | N |
| T/Y | 0.5831 | likely_pathogenic | 0.6292 | pathogenic | -0.484 | Destabilizing | 0.906 | D | 0.745 | 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.