Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30061 | 90406;90407;90408 | chr2:178552719;178552718;178552717 | chr2:179417446;179417445;179417444 |
| N2AB | 28420 | 85483;85484;85485 | chr2:178552719;178552718;178552717 | chr2:179417446;179417445;179417444 |
| N2A | 27493 | 82702;82703;82704 | chr2:178552719;178552718;178552717 | chr2:179417446;179417445;179417444 |
| N2B | 20996 | 63211;63212;63213 | chr2:178552719;178552718;178552717 | chr2:179417446;179417445;179417444 |
| Novex-1 | 21121 | 63586;63587;63588 | chr2:178552719;178552718;178552717 | chr2:179417446;179417445;179417444 |
| Novex-2 | 21188 | 63787;63788;63789 | chr2:178552719;178552718;178552717 | chr2:179417446;179417445;179417444 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/I | rs138958733  |
0.009 | None | N | 0.059 | 0.049 | None | gnomAD-2.1.1 | 4.99E-05 | None | None | None | None | I | None | 4.54545E-04 | 2.83E-05 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 7.8E-06 | 0 |
| V/I | rs138958733 |
0.009 | None | N | 0.059 | 0.049 | None | gnomAD-3.1.2 | 1.11713E-04 | None | None | None | None | I | None | 4.10133E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs138958733 |
0.009 | None | N | 0.059 | 0.049 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| V/I | rs138958733 |
0.009 | None | N | 0.059 | 0.049 | None | gnomAD-4.0.0 | 2.66433E-05 | None | None | None | None | I | None | 3.3312E-04 | 1.66639E-05 | None | 0 | 0 | None | 0 | 0 | 9.32344E-06 | 5.48932E-05 | 1.60036E-05 |
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 | 0.1606 | likely_benign | 0.1685 | benign | -0.459 | Destabilizing | 0.005 | N | 0.211 | neutral | N | 0.373006379 | None | None | I |
| V/C | 0.6771 | likely_pathogenic | 0.6785 | pathogenic | -0.557 | Destabilizing | 0.628 | D | 0.463 | neutral | None | None | None | None | I |
| V/D | 0.3742 | ambiguous | 0.3776 | ambiguous | -0.159 | Destabilizing | 0.055 | N | 0.579 | neutral | N | 0.363058744 | None | None | I |
| V/E | 0.3435 | ambiguous | 0.3559 | ambiguous | -0.283 | Destabilizing | 0.072 | N | 0.559 | neutral | None | None | None | None | I |
| V/F | 0.1662 | likely_benign | 0.155 | benign | -0.791 | Destabilizing | 0.07 | N | 0.48 | neutral | N | 0.472613226 | None | None | I |
| V/G | 0.2224 | likely_benign | 0.2225 | benign | -0.579 | Destabilizing | 0.029 | N | 0.554 | neutral | N | 0.404849439 | None | None | I |
| V/H | 0.4844 | ambiguous | 0.4898 | ambiguous | -0.215 | Destabilizing | None | N | 0.191 | neutral | None | None | None | None | I |
| V/I | 0.0707 | likely_benign | 0.069 | benign | -0.299 | Destabilizing | None | N | 0.059 | neutral | N | 0.419568175 | None | None | I |
| V/K | 0.3605 | ambiguous | 0.3933 | ambiguous | -0.261 | Destabilizing | 0.038 | N | 0.53 | neutral | None | None | None | None | I |
| V/L | 0.1468 | likely_benign | 0.1405 | benign | -0.299 | Destabilizing | None | N | 0.069 | neutral | N | 0.423781916 | None | None | I |
| V/M | 0.133 | likely_benign | 0.1259 | benign | -0.22 | Destabilizing | 0.214 | N | 0.317 | neutral | None | None | None | None | I |
| V/N | 0.2154 | likely_benign | 0.219 | benign | 0.008 | Stabilizing | 0.038 | N | 0.575 | neutral | None | None | None | None | I |
| V/P | 0.2974 | likely_benign | 0.3056 | benign | -0.318 | Destabilizing | 0.356 | N | 0.533 | neutral | None | None | None | None | I |
| V/Q | 0.3105 | likely_benign | 0.3233 | benign | -0.267 | Destabilizing | 0.214 | N | 0.532 | neutral | None | None | None | None | I |
| V/R | 0.319 | likely_benign | 0.3374 | benign | 0.233 | Stabilizing | 0.072 | N | 0.556 | neutral | None | None | None | None | I |
| V/S | 0.1855 | likely_benign | 0.1881 | benign | -0.376 | Destabilizing | 0.001 | N | 0.213 | neutral | None | None | None | None | I |
| V/T | 0.189 | likely_benign | 0.199 | benign | -0.399 | Destabilizing | 0.016 | N | 0.244 | neutral | None | None | None | None | I |
| V/W | 0.7809 | likely_pathogenic | 0.7722 | pathogenic | -0.851 | Destabilizing | 0.864 | D | 0.505 | neutral | None | None | None | None | I |
| V/Y | 0.4761 | ambiguous | 0.4669 | ambiguous | -0.525 | Destabilizing | 0.001 | N | 0.187 | 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.