Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2745 | 8458;8459;8460 | chr2:178770559;178770558;178770557 | chr2:179635286;179635285;179635284 |
| N2AB | 2745 | 8458;8459;8460 | chr2:178770559;178770558;178770557 | chr2:179635286;179635285;179635284 |
| N2A | 2745 | 8458;8459;8460 | chr2:178770559;178770558;178770557 | chr2:179635286;179635285;179635284 |
| N2B | 2699 | 8320;8321;8322 | chr2:178770559;178770558;178770557 | chr2:179635286;179635285;179635284 |
| Novex-1 | 2699 | 8320;8321;8322 | chr2:178770559;178770558;178770557 | chr2:179635286;179635285;179635284 |
| Novex-2 | 2699 | 8320;8321;8322 | chr2:178770559;178770558;178770557 | chr2:179635286;179635285;179635284 |
| Novex-3 | 2745 | 8458;8459;8460 | chr2:178770559;178770558;178770557 | chr2:179635286;179635285;179635284 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/D | rs759392982  |
-0.01 | 0.991 | D | 0.65 | 0.665 | 0.783227217476 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.81E-06 | 0 |
| V/D | rs759392982 |
-0.01 | 0.991 | D | 0.65 | 0.665 | 0.783227217476 | gnomAD-4.0.0 | 1.59049E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85649E-06 | 0 | 0 |
| V/I | rs1415984785 |
0.039 | 0.99 | D | 0.44 | 0.276 | 0.586295999888 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| V/I | rs1415984785 |
0.039 | 0.99 | D | 0.44 | 0.276 | 0.586295999888 | gnomAD-4.0.0 | 1.59049E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43271E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1266 | likely_benign | 0.1249 | benign | -0.557 | Destabilizing | 0.76 | D | 0.427 | neutral | D | 0.536172709 | None | None | I |
| V/C | 0.6971 | likely_pathogenic | 0.6967 | pathogenic | -0.818 | Destabilizing | 0.999 | D | 0.536 | neutral | None | None | None | None | I |
| V/D | 0.2225 | likely_benign | 0.2145 | benign | -0.314 | Destabilizing | 0.991 | D | 0.65 | neutral | D | 0.604854591 | None | None | I |
| V/E | 0.1944 | likely_benign | 0.1642 | benign | -0.396 | Destabilizing | 0.993 | D | 0.583 | neutral | None | None | None | None | I |
| V/F | 0.1405 | likely_benign | 0.1368 | benign | -0.61 | Destabilizing | 0.997 | D | 0.539 | neutral | D | 0.647310523 | None | None | I |
| V/G | 0.2055 | likely_benign | 0.2176 | benign | -0.707 | Destabilizing | 0.046 | N | 0.402 | neutral | D | 0.646719307 | None | None | I |
| V/H | 0.3978 | ambiguous | 0.3708 | ambiguous | -0.113 | Destabilizing | 0.999 | D | 0.619 | neutral | None | None | None | None | I |
| V/I | 0.0733 | likely_benign | 0.0691 | benign | -0.297 | Destabilizing | 0.99 | D | 0.44 | neutral | D | 0.550701351 | None | None | I |
| V/K | 0.2403 | likely_benign | 0.2038 | benign | -0.591 | Destabilizing | 0.993 | D | 0.58 | neutral | None | None | None | None | I |
| V/L | 0.1734 | likely_benign | 0.1641 | benign | -0.297 | Destabilizing | 0.928 | D | 0.431 | neutral | D | 0.53114888 | None | None | I |
| V/M | 0.1119 | likely_benign | 0.0993 | benign | -0.515 | Destabilizing | 0.998 | D | 0.487 | neutral | None | None | None | None | I |
| V/N | 0.1593 | likely_benign | 0.1451 | benign | -0.472 | Destabilizing | 0.986 | D | 0.646 | neutral | None | None | None | None | I |
| V/P | 0.8203 | likely_pathogenic | 0.8815 | pathogenic | -0.35 | Destabilizing | 0.998 | D | 0.568 | neutral | None | None | None | None | I |
| V/Q | 0.2266 | likely_benign | 0.1921 | benign | -0.653 | Destabilizing | 0.998 | D | 0.572 | neutral | None | None | None | None | I |
| V/R | 0.2242 | likely_benign | 0.1903 | benign | -0.072 | Destabilizing | 0.993 | D | 0.647 | neutral | None | None | None | None | I |
| V/S | 0.1519 | likely_benign | 0.1518 | benign | -0.851 | Destabilizing | 0.986 | D | 0.481 | neutral | None | None | None | None | I |
| V/T | 0.1385 | likely_benign | 0.1296 | benign | -0.828 | Destabilizing | 0.976 | D | 0.414 | neutral | None | None | None | None | I |
| V/W | 0.7611 | likely_pathogenic | 0.7468 | pathogenic | -0.699 | Destabilizing | 0.999 | D | 0.637 | neutral | None | None | None | None | I |
| V/Y | 0.4274 | ambiguous | 0.4264 | ambiguous | -0.423 | Destabilizing | 0.998 | D | 0.543 | neutral | None | None | None | None | I |
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.