Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27869 | 83830;83831;83832 | chr2:178562527;178562526;178562525 | chr2:179427254;179427253;179427252 |
| N2AB | 26228 | 78907;78908;78909 | chr2:178562527;178562526;178562525 | chr2:179427254;179427253;179427252 |
| N2A | 25301 | 76126;76127;76128 | chr2:178562527;178562526;178562525 | chr2:179427254;179427253;179427252 |
| N2B | 18804 | 56635;56636;56637 | chr2:178562527;178562526;178562525 | chr2:179427254;179427253;179427252 |
| Novex-1 | 18929 | 57010;57011;57012 | chr2:178562527;178562526;178562525 | chr2:179427254;179427253;179427252 |
| Novex-2 | 18996 | 57211;57212;57213 | chr2:178562527;178562526;178562525 | chr2:179427254;179427253;179427252 |
| 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/I | None | None | 0.966 | N | 0.42 | 0.317 | 0.506311303838 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| R/K | rs1286079244  |
0.073 | 0.002 | N | 0.136 | 0.086 | 0.249502417897 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 1.14811E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/K | rs1286079244 |
0.073 | 0.002 | N | 0.136 | 0.086 | 0.249502417897 | 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/K | rs1286079244 |
0.073 | 0.002 | N | 0.136 | 0.086 | 0.249502417897 | gnomAD-4.0.0 | 3.04486E-06 | None | None | None | None | N | None | 5.24219E-05 | 0 | None | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.4613 | ambiguous | 0.5152 | ambiguous | 0.061 | Stabilizing | 0.688 | D | 0.457 | neutral | None | None | None | None | N |
| R/C | 0.3426 | ambiguous | 0.3928 | ambiguous | -0.105 | Destabilizing | 0.998 | D | 0.365 | neutral | None | None | None | None | N |
| R/D | 0.7226 | likely_pathogenic | 0.7637 | pathogenic | -0.146 | Destabilizing | 0.842 | D | 0.463 | neutral | None | None | None | None | N |
| R/E | 0.4794 | ambiguous | 0.5341 | ambiguous | -0.085 | Destabilizing | 0.525 | D | 0.437 | neutral | None | None | None | None | N |
| R/F | 0.6522 | likely_pathogenic | 0.7049 | pathogenic | -0.162 | Destabilizing | 0.991 | D | 0.389 | neutral | None | None | None | None | N |
| R/G | 0.3674 | ambiguous | 0.4322 | ambiguous | -0.125 | Destabilizing | 0.801 | D | 0.442 | neutral | N | 0.441191454 | None | None | N |
| R/H | 0.1521 | likely_benign | 0.1726 | benign | -0.638 | Destabilizing | 0.991 | D | 0.476 | neutral | None | None | None | None | N |
| R/I | 0.3672 | ambiguous | 0.4196 | ambiguous | 0.513 | Stabilizing | 0.966 | D | 0.42 | neutral | N | 0.490332195 | None | None | N |
| R/K | 0.0949 | likely_benign | 0.102 | benign | -0.038 | Destabilizing | 0.002 | N | 0.136 | neutral | N | 0.340491316 | None | None | N |
| R/L | 0.3299 | likely_benign | 0.3832 | ambiguous | 0.513 | Stabilizing | 0.842 | D | 0.442 | neutral | None | None | None | None | N |
| R/M | 0.321 | likely_benign | 0.3782 | ambiguous | 0.051 | Stabilizing | 0.991 | D | 0.447 | neutral | None | None | None | None | N |
| R/N | 0.5833 | likely_pathogenic | 0.6398 | pathogenic | 0.156 | Stabilizing | 0.842 | D | 0.405 | neutral | None | None | None | None | N |
| R/P | 0.5944 | likely_pathogenic | 0.6397 | pathogenic | 0.383 | Stabilizing | 0.915 | D | 0.444 | neutral | None | None | None | None | N |
| R/Q | 0.1445 | likely_benign | 0.1633 | benign | 0.079 | Stabilizing | 0.842 | D | 0.431 | neutral | None | None | None | None | N |
| R/S | 0.5639 | ambiguous | 0.6267 | pathogenic | -0.123 | Destabilizing | 0.625 | D | 0.436 | neutral | N | 0.425147353 | None | None | N |
| R/T | 0.3144 | likely_benign | 0.3673 | ambiguous | 0.064 | Stabilizing | 0.801 | D | 0.463 | neutral | N | 0.441847602 | None | None | N |
| R/V | 0.4492 | ambiguous | 0.4976 | ambiguous | 0.383 | Stabilizing | 0.915 | D | 0.461 | neutral | None | None | None | None | N |
| R/W | 0.2967 | likely_benign | 0.3474 | ambiguous | -0.258 | Destabilizing | 0.998 | D | 0.422 | neutral | None | None | None | None | N |
| R/Y | 0.5155 | ambiguous | 0.5752 | pathogenic | 0.152 | Stabilizing | 0.991 | D | 0.421 | 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.