Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31606 | 95041;95042;95043 | chr2:178546612;178546611;178546610 | chr2:179411339;179411338;179411337 |
| N2AB | 29965 | 90118;90119;90120 | chr2:178546612;178546611;178546610 | chr2:179411339;179411338;179411337 |
| N2A | 29038 | 87337;87338;87339 | chr2:178546612;178546611;178546610 | chr2:179411339;179411338;179411337 |
| N2B | 22541 | 67846;67847;67848 | chr2:178546612;178546611;178546610 | chr2:179411339;179411338;179411337 |
| Novex-1 | 22666 | 68221;68222;68223 | chr2:178546612;178546611;178546610 | chr2:179411339;179411338;179411337 |
| Novex-2 | 22733 | 68422;68423;68424 | chr2:178546612;178546611;178546610 | chr2:179411339;179411338;179411337 |
| 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/Q | rs371840978  |
-0.313 | 0.071 | N | 0.297 | 0.089 | None | gnomAD-2.1.1 | 1.22E-05 | None | None | None | None | N | None | 1.2945E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9E-06 | 0 |
| R/Q | rs371840978 |
-0.313 | 0.071 | N | 0.297 | 0.089 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| R/Q | rs371840978 |
-0.313 | 0.071 | N | 0.297 | 0.089 | None | gnomAD-4.0.0 | 1.42992E-05 | None | None | None | None | N | None | 1.06935E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 1.10576E-05 | 1.10047E-05 | 1.60705E-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 | 0.3807 | ambiguous | 0.4285 | ambiguous | -0.181 | Destabilizing | 0.007 | N | 0.241 | neutral | None | None | None | None | N |
| R/C | 0.1521 | likely_benign | 0.1918 | benign | -0.09 | Destabilizing | 0.747 | D | 0.37 | neutral | None | None | None | None | N |
| R/D | 0.7481 | likely_pathogenic | 0.8035 | pathogenic | 0.016 | Stabilizing | 0.035 | N | 0.437 | neutral | None | None | None | None | N |
| R/E | 0.3833 | ambiguous | 0.4213 | ambiguous | 0.095 | Stabilizing | 0.007 | N | 0.159 | neutral | None | None | None | None | N |
| R/F | 0.4779 | ambiguous | 0.5755 | pathogenic | -0.271 | Destabilizing | 0.112 | N | 0.484 | neutral | None | None | None | None | N |
| R/G | 0.3178 | likely_benign | 0.3742 | ambiguous | -0.426 | Destabilizing | 0.028 | N | 0.317 | neutral | N | 0.471130359 | None | None | N |
| R/H | 0.0906 | likely_benign | 0.1114 | benign | -0.897 | Destabilizing | None | N | 0.099 | neutral | None | None | None | None | N |
| R/I | 0.257 | likely_benign | 0.2815 | benign | 0.444 | Stabilizing | 0.018 | N | 0.462 | neutral | None | None | None | None | N |
| R/K | 0.0885 | likely_benign | 0.0857 | benign | -0.163 | Destabilizing | None | N | 0.049 | neutral | None | None | None | None | N |
| R/L | 0.224 | likely_benign | 0.2741 | benign | 0.444 | Stabilizing | None | N | 0.137 | neutral | N | 0.493447071 | None | None | N |
| R/M | 0.272 | likely_benign | 0.2932 | benign | 0.123 | Stabilizing | 0.112 | N | 0.431 | neutral | None | None | None | None | N |
| R/N | 0.5499 | ambiguous | 0.6497 | pathogenic | 0.296 | Stabilizing | 0.018 | N | 0.211 | neutral | None | None | None | None | N |
| R/P | 0.9241 | likely_pathogenic | 0.941 | pathogenic | 0.257 | Stabilizing | 0.123 | N | 0.437 | neutral | N | 0.508571239 | None | None | N |
| R/Q | 0.0929 | likely_benign | 0.0964 | benign | 0.115 | Stabilizing | 0.071 | N | 0.297 | neutral | N | 0.460489291 | None | None | N |
| R/S | 0.436 | ambiguous | 0.5072 | ambiguous | -0.217 | Destabilizing | 0.007 | N | 0.258 | neutral | None | None | None | None | N |
| R/T | 0.2317 | likely_benign | 0.2501 | benign | 0.012 | Stabilizing | 0.015 | N | 0.324 | neutral | None | None | None | None | N |
| R/V | 0.2986 | likely_benign | 0.3325 | benign | 0.257 | Stabilizing | 0.007 | N | 0.364 | neutral | None | None | None | None | N |
| R/W | 0.1974 | likely_benign | 0.2332 | benign | -0.17 | Destabilizing | 0.747 | D | 0.349 | neutral | None | None | None | None | N |
| R/Y | 0.3814 | ambiguous | 0.4714 | ambiguous | 0.204 | Stabilizing | 0.018 | N | 0.45 | neutral | 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.