Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15838 | 47737;47738;47739 | chr2:178617839;178617838;178617837 | chr2:179482566;179482565;179482564 |
| N2AB | 14197 | 42814;42815;42816 | chr2:178617839;178617838;178617837 | chr2:179482566;179482565;179482564 |
| N2A | 13270 | 40033;40034;40035 | chr2:178617839;178617838;178617837 | chr2:179482566;179482565;179482564 |
| N2B | 6773 | 20542;20543;20544 | chr2:178617839;178617838;178617837 | chr2:179482566;179482565;179482564 |
| Novex-1 | 6898 | 20917;20918;20919 | chr2:178617839;178617838;178617837 | chr2:179482566;179482565;179482564 |
| Novex-2 | 6965 | 21118;21119;21120 | chr2:178617839;178617838;178617837 | chr2:179482566;179482565;179482564 |
| 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/G | None | None | 0.653 | N | 0.394 | 0.163 | 0.378498632473 | gnomAD-4.0.0 | 6.84684E-07 | None | None | None | None | I | None | 2.99509E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/L | rs199640194  |
None | 0.124 | N | 0.357 | 0.234 | 0.457106177737 | gnomAD-4.0.0 | 1.3694E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79995E-06 | 0 | 0 |
| R/Q | rs199640194 |
0.025 | 0.054 | N | 0.127 | 0.082 | None | gnomAD-2.1.1 | 2.79342E-04 | None | None | None | None | I | None | 1.6559E-04 | 1.13392E-04 | None | 0 | 5.17E-05 | None | 1.30762E-04 | None | 1.19952E-04 | 4.78694E-04 | 1.40766E-04 |
| R/Q | rs199640194 |
0.025 | 0.054 | N | 0.127 | 0.082 | None | gnomAD-3.1.2 | 2.50109E-04 | None | None | None | None | I | None | 2.65636E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 3.68091E-04 | 4.14422E-04 | 0 |
| R/Q | rs199640194 |
0.025 | 0.054 | N | 0.127 | 0.082 | None | gnomAD-4.0.0 | 4.66379E-04 | None | None | None | None | I | None | 2.00545E-04 | 1.33578E-04 | None | 0 | 0 | None | 2.18729E-04 | 1.64745E-04 | 5.78426E-04 | 1.64766E-04 | 2.72576E-04 |
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 | 0.3088 | likely_benign | 0.2888 | benign | -0.061 | Destabilizing | 0.3 | N | 0.306 | neutral | None | None | None | None | I |
| R/C | 0.2659 | likely_benign | 0.228 | benign | -0.215 | Destabilizing | 0.995 | D | 0.408 | neutral | None | None | None | None | I |
| R/D | 0.5753 | likely_pathogenic | 0.5371 | ambiguous | -0.137 | Destabilizing | 0.704 | D | 0.471 | neutral | None | None | None | None | I |
| R/E | 0.325 | likely_benign | 0.2934 | benign | -0.076 | Destabilizing | 0.329 | N | 0.227 | neutral | None | None | None | None | I |
| R/F | 0.5599 | ambiguous | 0.5545 | ambiguous | -0.308 | Destabilizing | 0.893 | D | 0.473 | neutral | None | None | None | None | I |
| R/G | 0.24 | likely_benign | 0.231 | benign | -0.252 | Destabilizing | 0.653 | D | 0.394 | neutral | N | 0.466752518 | None | None | I |
| R/H | 0.1371 | likely_benign | 0.1246 | benign | -0.759 | Destabilizing | 0.944 | D | 0.313 | neutral | None | None | None | None | I |
| R/I | 0.2453 | likely_benign | 0.2346 | benign | 0.405 | Stabilizing | 0.329 | N | 0.431 | neutral | None | None | None | None | I |
| R/K | 0.1183 | likely_benign | 0.102 | benign | -0.152 | Destabilizing | 0.004 | N | 0.05 | neutral | None | None | None | None | I |
| R/L | 0.2276 | likely_benign | 0.2233 | benign | 0.405 | Stabilizing | 0.124 | N | 0.357 | neutral | N | 0.451539813 | None | None | I |
| R/M | 0.2805 | likely_benign | 0.2659 | benign | 0.009 | Stabilizing | 0.085 | N | 0.248 | neutral | None | None | None | None | I |
| R/N | 0.4589 | ambiguous | 0.4368 | ambiguous | 0.065 | Stabilizing | 0.704 | D | 0.286 | neutral | None | None | None | None | I |
| R/P | 0.4674 | ambiguous | 0.441 | ambiguous | 0.27 | Stabilizing | 0.902 | D | 0.521 | neutral | N | 0.474440396 | None | None | I |
| R/Q | 0.1068 | likely_benign | 0.098 | benign | -0.037 | Destabilizing | 0.054 | N | 0.127 | neutral | N | 0.452404723 | None | None | I |
| R/S | 0.3896 | ambiguous | 0.3687 | ambiguous | -0.283 | Destabilizing | 0.495 | N | 0.373 | neutral | None | None | None | None | I |
| R/T | 0.2327 | likely_benign | 0.216 | benign | -0.088 | Destabilizing | 0.495 | N | 0.375 | neutral | None | None | None | None | I |
| R/V | 0.3049 | likely_benign | 0.2791 | benign | 0.27 | Stabilizing | 0.013 | N | 0.178 | neutral | None | None | None | None | I |
| R/W | 0.2849 | likely_benign | 0.2844 | benign | -0.364 | Destabilizing | 0.995 | D | 0.401 | neutral | None | None | None | None | I |
| R/Y | 0.4406 | ambiguous | 0.4108 | ambiguous | 0.047 | Stabilizing | 0.944 | D | 0.473 | 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.