Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20668 | 62227;62228;62229 | chr2:178589723;178589722;178589721 | chr2:179454450;179454449;179454448 |
| N2AB | 19027 | 57304;57305;57306 | chr2:178589723;178589722;178589721 | chr2:179454450;179454449;179454448 |
| N2A | 18100 | 54523;54524;54525 | chr2:178589723;178589722;178589721 | chr2:179454450;179454449;179454448 |
| N2B | 11603 | 35032;35033;35034 | chr2:178589723;178589722;178589721 | chr2:179454450;179454449;179454448 |
| Novex-1 | 11728 | 35407;35408;35409 | chr2:178589723;178589722;178589721 | chr2:179454450;179454449;179454448 |
| Novex-2 | 11795 | 35608;35609;35610 | chr2:178589723;178589722;178589721 | chr2:179454450;179454449;179454448 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/I | None | None | 0.641 | N | 0.476 | 0.159 | 0.359151904892 | gnomAD-4.0.0 | 6.84296E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.1595E-05 | 0 |
| R/K | rs1407338047  |
-0.382 | None | N | 0.081 | 0.102 | 0.202949470691 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| R/K | rs1407338047 |
-0.382 | None | N | 0.081 | 0.102 | 0.202949470691 | gnomAD-4.0.0 | 6.84296E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99582E-06 | 0 | 0 |
| R/S | None | None | 0.049 | N | 0.41 | 0.158 | 0.126345400529 | gnomAD-4.0.0 | 1.59174E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8594E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.6043 | likely_pathogenic | 0.5792 | pathogenic | -0.269 | Destabilizing | 0.064 | N | 0.412 | neutral | None | None | None | None | I |
| R/C | 0.3332 | likely_benign | 0.285 | benign | -0.412 | Destabilizing | 0.964 | D | 0.392 | neutral | None | None | None | None | I |
| R/D | 0.8914 | likely_pathogenic | 0.8905 | pathogenic | -0.152 | Destabilizing | 0.143 | N | 0.487 | neutral | None | None | None | None | I |
| R/E | 0.5924 | likely_pathogenic | 0.5884 | pathogenic | -0.11 | Destabilizing | 0.064 | N | 0.335 | neutral | None | None | None | None | I |
| R/F | 0.7809 | likely_pathogenic | 0.7306 | pathogenic | -0.578 | Destabilizing | 0.878 | D | 0.466 | neutral | None | None | None | None | I |
| R/G | 0.625 | likely_pathogenic | 0.5667 | pathogenic | -0.429 | Destabilizing | 0.094 | N | 0.432 | neutral | N | 0.489443974 | None | None | I |
| R/H | 0.1909 | likely_benign | 0.1897 | benign | -0.785 | Destabilizing | 0.703 | D | 0.358 | neutral | None | None | None | None | I |
| R/I | 0.3913 | ambiguous | 0.3119 | benign | 0.111 | Stabilizing | 0.641 | D | 0.476 | neutral | N | 0.435878848 | None | None | I |
| R/K | 0.0919 | likely_benign | 0.0876 | benign | -0.316 | Destabilizing | None | N | 0.081 | neutral | N | 0.370328646 | None | None | I |
| R/L | 0.4146 | ambiguous | 0.3875 | ambiguous | 0.111 | Stabilizing | 0.25 | N | 0.477 | neutral | None | None | None | None | I |
| R/M | 0.488 | ambiguous | 0.422 | ambiguous | -0.138 | Destabilizing | 0.878 | D | 0.424 | neutral | None | None | None | None | I |
| R/N | 0.7831 | likely_pathogenic | 0.7446 | pathogenic | -0.039 | Destabilizing | 0.002 | N | 0.093 | neutral | None | None | None | None | I |
| R/P | 0.6316 | likely_pathogenic | 0.6814 | pathogenic | 0.003 | Stabilizing | 0.403 | N | 0.46 | neutral | None | None | None | None | I |
| R/Q | 0.1795 | likely_benign | 0.1715 | benign | -0.218 | Destabilizing | 0.143 | N | 0.415 | neutral | None | None | None | None | I |
| R/S | 0.7303 | likely_pathogenic | 0.6923 | pathogenic | -0.477 | Destabilizing | 0.049 | N | 0.41 | neutral | N | 0.470242138 | None | None | I |
| R/T | 0.4216 | ambiguous | 0.361 | ambiguous | -0.315 | Destabilizing | 0.094 | N | 0.446 | neutral | N | 0.398880685 | None | None | I |
| R/V | 0.4603 | ambiguous | 0.4089 | ambiguous | 0.003 | Stabilizing | 0.25 | N | 0.495 | neutral | None | None | None | None | I |
| R/W | 0.5327 | ambiguous | 0.4884 | ambiguous | -0.59 | Destabilizing | 0.964 | D | 0.426 | neutral | None | None | None | None | I |
| R/Y | 0.6862 | likely_pathogenic | 0.6356 | pathogenic | -0.199 | Destabilizing | 0.878 | D | 0.489 | 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.