Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31670 | 95233;95234;95235 | chr2:178546323;178546322;178546321 | chr2:179411050;179411049;179411048 |
| N2AB | 30029 | 90310;90311;90312 | chr2:178546323;178546322;178546321 | chr2:179411050;179411049;179411048 |
| N2A | 29102 | 87529;87530;87531 | chr2:178546323;178546322;178546321 | chr2:179411050;179411049;179411048 |
| N2B | 22605 | 68038;68039;68040 | chr2:178546323;178546322;178546321 | chr2:179411050;179411049;179411048 |
| Novex-1 | 22730 | 68413;68414;68415 | chr2:178546323;178546322;178546321 | chr2:179411050;179411049;179411048 |
| Novex-2 | 22797 | 68614;68615;68616 | chr2:178546323;178546322;178546321 | chr2:179411050;179411049;179411048 |
| 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 | rs750410616  |
-0.052 | 0.997 | N | 0.606 | 0.334 | 0.28297238246 | gnomAD-2.1.1 | 2.41E-05 | None | None | None | None | N | None | 0 | 1.73792E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/Q | rs750410616 |
-0.052 | 0.997 | N | 0.606 | 0.334 | 0.28297238246 | gnomAD-4.0.0 | 9.57883E-06 | None | None | None | None | N | None | 0 | 1.78883E-04 | None | 0 | 0 | None | 0 | 0 | 2.69842E-06 | 3.47802E-05 | 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 | 0.5766 | likely_pathogenic | 0.558 | ambiguous | -0.835 | Destabilizing | 0.953 | D | 0.609 | neutral | None | None | None | None | N |
| R/C | 0.2249 | likely_benign | 0.2182 | benign | -0.752 | Destabilizing | 0.999 | D | 0.733 | prob.delet. | None | None | None | None | N |
| R/D | 0.8214 | likely_pathogenic | 0.8064 | pathogenic | -0.353 | Destabilizing | 0.986 | D | 0.645 | neutral | None | None | None | None | N |
| R/E | 0.5528 | ambiguous | 0.527 | ambiguous | -0.278 | Destabilizing | 0.953 | D | 0.571 | neutral | None | None | None | None | N |
| R/F | 0.634 | likely_pathogenic | 0.6059 | pathogenic | -0.982 | Destabilizing | 0.993 | D | 0.731 | prob.delet. | None | None | None | None | N |
| R/G | 0.4508 | ambiguous | 0.4139 | ambiguous | -1.088 | Destabilizing | 0.975 | D | 0.618 | neutral | N | 0.492309 | None | None | N |
| R/H | 0.0929 | likely_benign | 0.093 | benign | -1.33 | Destabilizing | 0.128 | N | 0.353 | neutral | None | None | None | None | N |
| R/I | 0.3971 | ambiguous | 0.3791 | ambiguous | -0.171 | Destabilizing | 0.993 | D | 0.732 | prob.delet. | None | None | None | None | N |
| R/K | 0.1234 | likely_benign | 0.1171 | benign | -0.933 | Destabilizing | 0.893 | D | 0.519 | neutral | None | None | None | None | N |
| R/L | 0.3449 | ambiguous | 0.3373 | benign | -0.171 | Destabilizing | 0.993 | D | 0.615 | neutral | N | 0.488364617 | None | None | N |
| R/M | 0.3602 | ambiguous | 0.3407 | ambiguous | -0.238 | Destabilizing | 0.999 | D | 0.64 | neutral | None | None | None | None | N |
| R/N | 0.6545 | likely_pathogenic | 0.6222 | pathogenic | -0.311 | Destabilizing | 0.953 | D | 0.589 | neutral | None | None | None | None | N |
| R/P | 0.951 | likely_pathogenic | 0.9493 | pathogenic | -0.373 | Destabilizing | 0.999 | D | 0.703 | prob.neutral | N | 0.498836742 | None | None | N |
| R/Q | 0.1237 | likely_benign | 0.1248 | benign | -0.627 | Destabilizing | 0.997 | D | 0.606 | neutral | N | 0.508489174 | None | None | N |
| R/S | 0.6536 | likely_pathogenic | 0.6217 | pathogenic | -1.039 | Destabilizing | 0.953 | D | 0.631 | neutral | None | None | None | None | N |
| R/T | 0.3295 | likely_benign | 0.313 | benign | -0.813 | Destabilizing | 0.993 | D | 0.613 | neutral | None | None | None | None | N |
| R/V | 0.4781 | ambiguous | 0.4582 | ambiguous | -0.373 | Destabilizing | 0.993 | D | 0.726 | prob.delet. | None | None | None | None | N |
| R/W | 0.2262 | likely_benign | 0.2249 | benign | -0.692 | Destabilizing | 0.999 | D | 0.731 | prob.delet. | None | None | None | None | N |
| R/Y | 0.4 | ambiguous | 0.3874 | ambiguous | -0.354 | Destabilizing | 0.986 | D | 0.712 | prob.delet. | 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.