Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15710 | 47353;47354;47355 | chr2:178618330;178618329;178618328 | chr2:179483057;179483056;179483055 |
| N2AB | 14069 | 42430;42431;42432 | chr2:178618330;178618329;178618328 | chr2:179483057;179483056;179483055 |
| N2A | 13142 | 39649;39650;39651 | chr2:178618330;178618329;178618328 | chr2:179483057;179483056;179483055 |
| N2B | 6645 | 20158;20159;20160 | chr2:178618330;178618329;178618328 | chr2:179483057;179483056;179483055 |
| Novex-1 | 6770 | 20533;20534;20535 | chr2:178618330;178618329;178618328 | chr2:179483057;179483056;179483055 |
| Novex-2 | 6837 | 20734;20735;20736 | chr2:178618330;178618329;178618328 | chr2:179483057;179483056;179483055 |
| 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 | rs370669650  |
-0.077 | 0.022 | N | 0.318 | 0.215 | None | gnomAD-2.1.1 | 2.51E-05 | None | None | None | None | I | None | 4.14E-05 | 2.83E-05 | None | 0 | 0 | None | 9.81E-05 | None | 0 | 1.57E-05 | 0 |
| R/C | rs370669650 |
-0.077 | 0.022 | N | 0.318 | 0.215 | None | gnomAD-3.1.2 | 1.98E-05 | None | None | None | None | I | None | 4.84E-05 | 6.57E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/C | rs370669650 |
-0.077 | 0.022 | N | 0.318 | 0.215 | None | gnomAD-4.0.0 | 1.11634E-05 | None | None | None | None | I | None | 2.67473E-05 | 3.34091E-05 | None | 0 | 0 | None | 0 | 0 | 6.78477E-06 | 4.3929E-05 | 3.20554E-05 |
| R/G | None | None | 0.221 | N | 0.355 | 0.214 | 0.346315397577 | gnomAD-4.0.0 | 2.05387E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69968E-06 | 0 | 0 |
| R/H | rs185689179 |
-0.562 | 0.004 | N | 0.191 | 0.074 | None | gnomAD-2.1.1 | 4.3E-05 | None | None | None | None | I | None | 4.14E-05 | 2.83E-05 | None | 0 | 3.61944E-04 | None | 6.54E-05 | None | 0 | 7.85E-06 | 0 |
| R/H | rs185689179 |
-0.562 | 0.004 | N | 0.191 | 0.074 | None | gnomAD-3.1.2 | 4.61E-05 | None | None | None | None | I | None | 7.25E-05 | 0 | 0 | 0 | 5.84567E-04 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/H | rs185689179 |
-0.562 | 0.004 | N | 0.191 | 0.074 | None | gnomAD-4.0.0 | 2.54239E-05 | None | None | None | None | I | None | 6.67289E-05 | 1.66923E-05 | None | 0 | 1.79003E-04 | None | 3.12412E-05 | 0 | 1.52657E-05 | 6.58848E-05 | 1.6022E-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 | 0.3112 | likely_benign | 0.2729 | benign | 0.027 | Stabilizing | 0.129 | N | 0.303 | neutral | None | None | None | None | I |
| R/C | 0.2315 | likely_benign | 0.3197 | benign | -0.019 | Destabilizing | 0.022 | N | 0.318 | neutral | N | 0.464987624 | None | None | I |
| R/D | 0.5088 | ambiguous | 0.4489 | ambiguous | -0.183 | Destabilizing | 0.418 | N | 0.424 | neutral | None | None | None | None | I |
| R/E | 0.3073 | likely_benign | 0.2785 | benign | -0.136 | Destabilizing | 0.129 | N | 0.356 | neutral | None | None | None | None | I |
| R/F | 0.5137 | ambiguous | 0.4508 | ambiguous | -0.222 | Destabilizing | 0.836 | D | 0.327 | neutral | None | None | None | None | I |
| R/G | 0.216 | likely_benign | 0.2014 | benign | -0.147 | Destabilizing | 0.221 | N | 0.355 | neutral | N | 0.454956852 | None | None | I |
| R/H | 0.1002 | likely_benign | 0.1019 | benign | -0.663 | Destabilizing | 0.004 | N | 0.191 | neutral | N | 0.461207663 | None | None | I |
| R/I | 0.3131 | likely_benign | 0.2555 | benign | 0.446 | Stabilizing | 0.836 | D | 0.379 | neutral | None | None | None | None | I |
| R/K | 0.1075 | likely_benign | 0.1168 | benign | -0.023 | Destabilizing | 0.129 | N | 0.358 | neutral | None | None | None | None | I |
| R/L | 0.271 | likely_benign | 0.2418 | benign | 0.446 | Stabilizing | 0.579 | D | 0.368 | neutral | N | 0.47435382 | None | None | I |
| R/M | 0.2861 | likely_benign | 0.2563 | benign | 0.093 | Stabilizing | 0.94 | D | 0.36 | neutral | None | None | None | None | I |
| R/N | 0.3776 | ambiguous | 0.3398 | benign | 0.256 | Stabilizing | 0.264 | N | 0.347 | neutral | None | None | None | None | I |
| R/P | 0.855 | likely_pathogenic | 0.8201 | pathogenic | 0.326 | Stabilizing | 0.907 | D | 0.401 | neutral | N | 0.465091291 | None | None | I |
| R/Q | 0.1006 | likely_benign | 0.1045 | benign | 0.133 | Stabilizing | 0.027 | N | 0.256 | neutral | None | None | None | None | I |
| R/S | 0.3348 | likely_benign | 0.3076 | benign | -0.032 | Destabilizing | 0.018 | N | 0.255 | neutral | N | 0.434535188 | None | None | I |
| R/T | 0.1813 | likely_benign | 0.1584 | benign | 0.134 | Stabilizing | 0.264 | N | 0.379 | neutral | None | None | None | None | I |
| R/V | 0.348 | ambiguous | 0.2869 | benign | 0.326 | Stabilizing | 0.418 | N | 0.417 | neutral | None | None | None | None | I |
| R/W | 0.2509 | likely_benign | 0.2438 | benign | -0.311 | Destabilizing | 0.983 | D | 0.265 | neutral | None | None | None | None | I |
| R/Y | 0.383 | ambiguous | 0.3497 | ambiguous | 0.09 | Stabilizing | 0.716 | D | 0.4 | 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.