Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26925 | 80998;80999;81000 | chr2:178565359;178565358;178565357 | chr2:179430086;179430085;179430084 |
| N2AB | 25284 | 76075;76076;76077 | chr2:178565359;178565358;178565357 | chr2:179430086;179430085;179430084 |
| N2A | 24357 | 73294;73295;73296 | chr2:178565359;178565358;178565357 | chr2:179430086;179430085;179430084 |
| N2B | 17860 | 53803;53804;53805 | chr2:178565359;178565358;178565357 | chr2:179430086;179430085;179430084 |
| Novex-1 | 17985 | 54178;54179;54180 | chr2:178565359;178565358;178565357 | chr2:179430086;179430085;179430084 |
| Novex-2 | 18052 | 54379;54380;54381 | chr2:178565359;178565358;178565357 | chr2:179430086;179430085;179430084 |
| 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 | rs373948797  |
-1.139 | 0.892 | N | 0.391 | 0.347 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| R/G | rs373948797 |
-1.139 | 0.892 | N | 0.391 | 0.347 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/G | rs373948797 |
-1.139 | 0.892 | N | 0.391 | 0.347 | None | gnomAD-4.0.0 | 6.5735E-06 | None | None | None | None | N | None | 2.41231E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/K | rs748215561 |
-0.448 | 0.773 | N | 0.47 | 0.255 | 0.202949470691 | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 4.45E-05 | 0 |
| R/K | rs748215561 |
-0.448 | 0.773 | N | 0.47 | 0.255 | 0.202949470691 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/K | rs748215561 |
-0.448 | 0.773 | N | 0.47 | 0.255 | 0.202949470691 | gnomAD-4.0.0 | 1.79736E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.45831E-05 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.964 | likely_pathogenic | 0.9487 | pathogenic | -0.909 | Destabilizing | 0.916 | D | 0.386 | neutral | None | None | None | None | N |
| R/C | 0.7521 | likely_pathogenic | 0.7138 | pathogenic | -0.864 | Destabilizing | 0.999 | D | 0.571 | neutral | None | None | None | None | N |
| R/D | 0.9869 | likely_pathogenic | 0.9754 | pathogenic | -0.223 | Destabilizing | 0.033 | N | 0.288 | neutral | None | None | None | None | N |
| R/E | 0.9494 | likely_pathogenic | 0.9118 | pathogenic | -0.106 | Destabilizing | 0.845 | D | 0.401 | neutral | None | None | None | None | N |
| R/F | 0.9812 | likely_pathogenic | 0.974 | pathogenic | -0.813 | Destabilizing | 0.996 | D | 0.533 | neutral | None | None | None | None | N |
| R/G | 0.9421 | likely_pathogenic | 0.9199 | pathogenic | -1.216 | Destabilizing | 0.892 | D | 0.391 | neutral | N | 0.49404758 | None | None | N |
| R/H | 0.4481 | ambiguous | 0.4006 | ambiguous | -1.436 | Destabilizing | 0.996 | D | 0.395 | neutral | None | None | None | None | N |
| R/I | 0.9554 | likely_pathogenic | 0.9401 | pathogenic | -0.082 | Destabilizing | 0.983 | D | 0.531 | neutral | N | 0.50230324 | None | None | N |
| R/K | 0.5417 | ambiguous | 0.5087 | ambiguous | -0.995 | Destabilizing | 0.773 | D | 0.47 | neutral | N | 0.472825772 | None | None | N |
| R/L | 0.9189 | likely_pathogenic | 0.8992 | pathogenic | -0.082 | Destabilizing | 0.987 | D | 0.396 | neutral | None | None | None | None | N |
| R/M | 0.9512 | likely_pathogenic | 0.9346 | pathogenic | -0.312 | Destabilizing | 0.999 | D | 0.381 | neutral | None | None | None | None | N |
| R/N | 0.9702 | likely_pathogenic | 0.9497 | pathogenic | -0.418 | Destabilizing | 0.845 | D | 0.397 | neutral | None | None | None | None | N |
| R/P | 0.9942 | likely_pathogenic | 0.9909 | pathogenic | -0.337 | Destabilizing | 0.987 | D | 0.456 | neutral | None | None | None | None | N |
| R/Q | 0.5486 | ambiguous | 0.4856 | ambiguous | -0.624 | Destabilizing | 0.987 | D | 0.447 | neutral | None | None | None | None | N |
| R/S | 0.9695 | likely_pathogenic | 0.9586 | pathogenic | -1.206 | Destabilizing | 0.892 | D | 0.4 | neutral | N | 0.476196815 | None | None | N |
| R/T | 0.9408 | likely_pathogenic | 0.9178 | pathogenic | -0.912 | Destabilizing | 0.892 | D | 0.385 | neutral | N | 0.495453158 | None | None | N |
| R/V | 0.9646 | likely_pathogenic | 0.9493 | pathogenic | -0.337 | Destabilizing | 0.987 | D | 0.539 | neutral | None | None | None | None | N |
| R/W | 0.7359 | likely_pathogenic | 0.7008 | pathogenic | -0.449 | Destabilizing | 0.999 | D | 0.593 | neutral | None | None | None | None | N |
| R/Y | 0.9252 | likely_pathogenic | 0.9035 | pathogenic | -0.145 | Destabilizing | 0.996 | D | 0.442 | 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.