Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21547 | 64864;64865;64866 | chr2:178585105;178585104;178585103 | chr2:179449832;179449831;179449830 |
| N2AB | 19906 | 59941;59942;59943 | chr2:178585105;178585104;178585103 | chr2:179449832;179449831;179449830 |
| N2A | 18979 | 57160;57161;57162 | chr2:178585105;178585104;178585103 | chr2:179449832;179449831;179449830 |
| N2B | 12482 | 37669;37670;37671 | chr2:178585105;178585104;178585103 | chr2:179449832;179449831;179449830 |
| Novex-1 | 12607 | 38044;38045;38046 | chr2:178585105;178585104;178585103 | chr2:179449832;179449831;179449830 |
| Novex-2 | 12674 | 38245;38246;38247 | chr2:178585105;178585104;178585103 | chr2:179449832;179449831;179449830 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/K | rs528663658  |
-0.206 | None | N | 0.197 | 0.112 | 0.221734844693 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.3E-05 | None | 0 | 0 | 0 |
| T/K | rs528663658 |
-0.206 | None | N | 0.197 | 0.112 | 0.221734844693 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| T/K | rs528663658 |
-0.206 | None | N | 0.197 | 0.112 | 0.221734844693 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.21507E-04 | 0 |
| T/P | rs1357789824 |
-0.488 | 0.171 | N | 0.463 | 0.14 | 0.255777322467 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.67224E-04 | None | 0 | None | 0 | 0 | 0 |
| T/P | rs1357789824 |
-0.488 | 0.171 | N | 0.463 | 0.14 | 0.255777322467 | gnomAD-4.0.0 | 2.05536E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 7.56163E-05 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0706 | likely_benign | 0.0696 | benign | -0.348 | Destabilizing | 0.012 | N | 0.241 | neutral | D | 0.528093655 | None | None | N |
| T/C | 0.2185 | likely_benign | 0.2037 | benign | -0.102 | Destabilizing | 0.676 | D | 0.486 | neutral | None | None | None | None | N |
| T/D | 0.359 | ambiguous | 0.3301 | benign | -0.092 | Destabilizing | 0.038 | N | 0.469 | neutral | None | None | None | None | N |
| T/E | 0.2102 | likely_benign | 0.2014 | benign | -0.19 | Destabilizing | 0.038 | N | 0.401 | neutral | None | None | None | None | N |
| T/F | 0.1483 | likely_benign | 0.1353 | benign | -0.967 | Destabilizing | 0.214 | N | 0.584 | neutral | None | None | None | None | N |
| T/G | 0.1901 | likely_benign | 0.1708 | benign | -0.435 | Destabilizing | 0.038 | N | 0.511 | neutral | None | None | None | None | N |
| T/H | 0.1675 | likely_benign | 0.166 | benign | -0.81 | Destabilizing | 0.356 | N | 0.567 | neutral | None | None | None | None | N |
| T/I | 0.0851 | likely_benign | 0.0845 | benign | -0.239 | Destabilizing | 0.01 | N | 0.431 | neutral | N | 0.495810665 | None | None | N |
| T/K | 0.1119 | likely_benign | 0.1093 | benign | -0.27 | Destabilizing | None | N | 0.197 | neutral | N | 0.402318927 | None | None | N |
| T/L | 0.0784 | likely_benign | 0.0737 | benign | -0.239 | Destabilizing | 0.016 | N | 0.437 | neutral | None | None | None | None | N |
| T/M | 0.0712 | likely_benign | 0.0718 | benign | 0.115 | Stabilizing | 0.214 | N | 0.495 | neutral | None | None | None | None | N |
| T/N | 0.1039 | likely_benign | 0.0952 | benign | 0.014 | Stabilizing | 0.038 | N | 0.273 | neutral | None | None | None | None | N |
| T/P | 0.3331 | likely_benign | 0.3331 | benign | -0.25 | Destabilizing | 0.171 | N | 0.463 | neutral | N | 0.510721402 | None | None | N |
| T/Q | 0.1463 | likely_benign | 0.1447 | benign | -0.303 | Destabilizing | 0.072 | N | 0.467 | neutral | None | None | None | None | N |
| T/R | 0.1071 | likely_benign | 0.1044 | benign | 0.031 | Stabilizing | 0.001 | N | 0.293 | neutral | N | 0.476992831 | None | None | N |
| T/S | 0.085 | likely_benign | 0.0799 | benign | -0.152 | Destabilizing | None | N | 0.151 | neutral | N | 0.428198806 | None | None | N |
| T/V | 0.0756 | likely_benign | 0.0766 | benign | -0.25 | Destabilizing | None | N | 0.134 | neutral | None | None | None | None | N |
| T/W | 0.4379 | ambiguous | 0.4247 | ambiguous | -0.975 | Destabilizing | 0.864 | D | 0.596 | neutral | None | None | None | None | N |
| T/Y | 0.1979 | likely_benign | 0.182 | benign | -0.683 | Destabilizing | 0.356 | N | 0.583 | 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.