Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27893 | 83902;83903;83904 | chr2:178562455;178562454;178562453 | chr2:179427182;179427181;179427180 |
| N2AB | 26252 | 78979;78980;78981 | chr2:178562455;178562454;178562453 | chr2:179427182;179427181;179427180 |
| N2A | 25325 | 76198;76199;76200 | chr2:178562455;178562454;178562453 | chr2:179427182;179427181;179427180 |
| N2B | 18828 | 56707;56708;56709 | chr2:178562455;178562454;178562453 | chr2:179427182;179427181;179427180 |
| Novex-1 | 18953 | 57082;57083;57084 | chr2:178562455;178562454;178562453 | chr2:179427182;179427181;179427180 |
| Novex-2 | 19020 | 57283;57284;57285 | chr2:178562455;178562454;178562453 | chr2:179427182;179427181;179427180 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/R | rs761618267  |
-0.539 | 1.0 | N | 0.802 | 0.587 | 0.384584525793 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.28E-05 | None | 0 | 0 | 0 |
| S/R | rs761618267 |
-0.539 | 1.0 | N | 0.802 | 0.587 | 0.384584525793 | gnomAD-4.0.0 | 1.59279E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.4346E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.2149 | likely_benign | 0.2154 | benign | -0.53 | Destabilizing | 0.997 | D | 0.598 | neutral | None | None | None | None | N |
| S/C | 0.1987 | likely_benign | 0.218 | benign | -0.355 | Destabilizing | 1.0 | D | 0.793 | deleterious | N | 0.487844106 | None | None | N |
| S/D | 0.9241 | likely_pathogenic | 0.9379 | pathogenic | -0.494 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| S/E | 0.9407 | likely_pathogenic | 0.9573 | pathogenic | -0.545 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| S/F | 0.7263 | likely_pathogenic | 0.7655 | pathogenic | -0.92 | Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | N |
| S/G | 0.3067 | likely_benign | 0.3549 | ambiguous | -0.719 | Destabilizing | 1.0 | D | 0.584 | neutral | N | 0.471476781 | None | None | N |
| S/H | 0.848 | likely_pathogenic | 0.8685 | pathogenic | -1.3 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| S/I | 0.7513 | likely_pathogenic | 0.8221 | pathogenic | -0.147 | Destabilizing | 1.0 | D | 0.809 | deleterious | N | 0.515214298 | None | None | N |
| S/K | 0.9823 | likely_pathogenic | 0.9893 | pathogenic | -0.729 | Destabilizing | 1.0 | D | 0.706 | prob.neutral | None | None | None | None | N |
| S/L | 0.3633 | ambiguous | 0.4274 | ambiguous | -0.147 | Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | N |
| S/M | 0.5414 | ambiguous | 0.6022 | pathogenic | 0.296 | Stabilizing | 1.0 | D | 0.798 | deleterious | None | None | None | None | N |
| S/N | 0.5936 | likely_pathogenic | 0.6622 | pathogenic | -0.575 | Destabilizing | 0.997 | D | 0.696 | prob.neutral | N | 0.505174666 | None | None | N |
| S/P | 0.99 | likely_pathogenic | 0.9937 | pathogenic | -0.243 | Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| S/Q | 0.891 | likely_pathogenic | 0.9194 | pathogenic | -0.854 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| S/R | 0.9695 | likely_pathogenic | 0.9812 | pathogenic | -0.503 | Destabilizing | 1.0 | D | 0.802 | deleterious | N | 0.485536247 | None | None | N |
| S/T | 0.2461 | likely_benign | 0.2819 | benign | -0.591 | Destabilizing | 0.981 | D | 0.602 | neutral | N | 0.485829416 | None | None | N |
| S/V | 0.639 | likely_pathogenic | 0.7103 | pathogenic | -0.243 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| S/W | 0.8308 | likely_pathogenic | 0.8608 | pathogenic | -0.903 | Destabilizing | 1.0 | D | 0.812 | deleterious | None | None | None | None | N |
| S/Y | 0.7095 | likely_pathogenic | 0.7413 | pathogenic | -0.638 | Destabilizing | 1.0 | D | 0.827 | 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.