Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27688 | 83287;83288;83289 | chr2:178563070;178563069;178563068 | chr2:179427797;179427796;179427795 |
| N2AB | 26047 | 78364;78365;78366 | chr2:178563070;178563069;178563068 | chr2:179427797;179427796;179427795 |
| N2A | 25120 | 75583;75584;75585 | chr2:178563070;178563069;178563068 | chr2:179427797;179427796;179427795 |
| N2B | 18623 | 56092;56093;56094 | chr2:178563070;178563069;178563068 | chr2:179427797;179427796;179427795 |
| Novex-1 | 18748 | 56467;56468;56469 | chr2:178563070;178563069;178563068 | chr2:179427797;179427796;179427795 |
| Novex-2 | 18815 | 56668;56669;56670 | chr2:178563070;178563069;178563068 | chr2:179427797;179427796;179427795 |
| 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/C | rs757441189  |
-0.191 | 1.0 | D | 0.696 | 0.567 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| R/C | rs757441189 |
-0.191 | 1.0 | D | 0.696 | 0.567 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 6.32911E-03 | 0 | 0 | 0 |
| R/C | rs757441189 |
-0.191 | 1.0 | D | 0.696 | 0.567 | None | gnomAD-4.0.0 | 4.77432E-06 | None | None | None | None | I | None | 5.65739E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43271E-05 | 3.02444E-05 |
| R/H | rs185002960 |
-0.61 | 0.999 | N | 0.606 | 0.411 | None | gnomAD-2.1.1 | 3.72487E-03 | None | None | None | None | I | None | 3.3066E-04 | 1.69635E-04 | None | 1.93311E-04 | 3.07535E-04 | None | 1.96091E-04 | None | 3.14775E-02 | 1.62335E-03 | 2.94613E-03 |
| R/H | rs185002960 |
-0.61 | 0.999 | N | 0.606 | 0.411 | None | gnomAD-3.1.2 | 3.05147E-03 | None | None | None | None | I | None | 3.13813E-04 | 6.57E-05 | 0 | 2.88184E-04 | 0 | None | 3.23463E-02 | 0 | 1.47016E-03 | 2.07297E-04 | 2.39234E-03 |
| R/H | rs185002960 |
-0.61 | 0.999 | N | 0.606 | 0.411 | None | 1000 genomes | 1.39776E-03 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 6E-03 | None | None | None | 1E-03 | None |
| R/H | rs185002960 |
-0.61 | 0.999 | N | 0.606 | 0.411 | None | gnomAD-4.0.0 | 1.95397E-03 | None | None | None | None | I | None | 3.3328E-04 | 1.83425E-04 | None | 2.02716E-04 | 3.79041E-04 | None | 2.99128E-02 | 0 | 9.01918E-04 | 9.88186E-05 | 1.71271E-03 |
| R/L | None | None | 0.975 | N | 0.59 | 0.423 | 0.708922172023 | gnomAD-4.0.0 | 6.84244E-07 | None | None | None | None | I | None | 2.98829E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/P | rs185002960 |
0.319 | 0.109 | N | 0.545 | 0.39 | 0.519514513453 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/P | rs185002960 |
0.319 | 0.109 | N | 0.545 | 0.39 | 0.519514513453 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 9.66E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/P | rs185002960 |
0.319 | 0.109 | N | 0.545 | 0.39 | 0.519514513453 | gnomAD-4.0.0 | 4.33802E-06 | None | None | None | None | I | None | 7.99893E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.60067E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9502 | likely_pathogenic | 0.9608 | pathogenic | 0.036 | Stabilizing | 0.953 | D | 0.615 | neutral | None | None | None | None | I |
| R/C | 0.6926 | likely_pathogenic | 0.7576 | pathogenic | -0.237 | Destabilizing | 1.0 | D | 0.696 | prob.neutral | D | 0.527727871 | None | None | I |
| R/D | 0.9818 | likely_pathogenic | 0.9846 | pathogenic | -0.226 | Destabilizing | 0.993 | D | 0.615 | neutral | None | None | None | None | I |
| R/E | 0.9157 | likely_pathogenic | 0.9226 | pathogenic | -0.174 | Destabilizing | 0.953 | D | 0.639 | neutral | None | None | None | None | I |
| R/F | 0.9582 | likely_pathogenic | 0.9672 | pathogenic | -0.244 | Destabilizing | 0.999 | D | 0.661 | neutral | None | None | None | None | I |
| R/G | 0.8955 | likely_pathogenic | 0.9137 | pathogenic | -0.125 | Destabilizing | 0.975 | D | 0.6 | neutral | D | 0.537981313 | None | None | I |
| R/H | 0.2997 | likely_benign | 0.3646 | ambiguous | -0.599 | Destabilizing | 0.999 | D | 0.606 | neutral | N | 0.515611097 | None | None | I |
| R/I | 0.9412 | likely_pathogenic | 0.9442 | pathogenic | 0.419 | Stabilizing | 0.993 | D | 0.665 | neutral | None | None | None | None | I |
| R/K | 0.2591 | likely_benign | 0.3138 | benign | -0.123 | Destabilizing | 0.893 | D | 0.57 | neutral | None | None | None | None | I |
| R/L | 0.8285 | likely_pathogenic | 0.8487 | pathogenic | 0.419 | Stabilizing | 0.975 | D | 0.59 | neutral | N | 0.484073395 | None | None | I |
| R/M | 0.8978 | likely_pathogenic | 0.9108 | pathogenic | -0.042 | Destabilizing | 0.999 | D | 0.602 | neutral | None | None | None | None | I |
| R/N | 0.9628 | likely_pathogenic | 0.9692 | pathogenic | -0.026 | Destabilizing | 0.993 | D | 0.608 | neutral | None | None | None | None | I |
| R/P | 0.854 | likely_pathogenic | 0.9 | pathogenic | 0.31 | Stabilizing | 0.109 | N | 0.545 | neutral | N | 0.506647875 | None | None | I |
| R/Q | 0.368 | ambiguous | 0.4221 | ambiguous | -0.075 | Destabilizing | 0.993 | D | 0.613 | neutral | None | None | None | None | I |
| R/S | 0.9682 | likely_pathogenic | 0.9745 | pathogenic | -0.26 | Destabilizing | 0.975 | D | 0.603 | neutral | N | 0.49797046 | None | None | I |
| R/T | 0.931 | likely_pathogenic | 0.9398 | pathogenic | -0.09 | Destabilizing | 0.953 | D | 0.598 | neutral | None | None | None | None | I |
| R/V | 0.9453 | likely_pathogenic | 0.9476 | pathogenic | 0.31 | Stabilizing | 0.993 | D | 0.661 | neutral | None | None | None | None | I |
| R/W | 0.6647 | likely_pathogenic | 0.7135 | pathogenic | -0.387 | Destabilizing | 0.999 | D | 0.698 | prob.neutral | None | None | None | None | I |
| R/Y | 0.8751 | likely_pathogenic | 0.9009 | pathogenic | 0.027 | Stabilizing | 0.998 | D | 0.655 | 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.