Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3011 | 9256;9257;9258 | chr2:178768805;178768804;178768803 | chr2:179633532;179633531;179633530 |
| N2AB | 3011 | 9256;9257;9258 | chr2:178768805;178768804;178768803 | chr2:179633532;179633531;179633530 |
| N2A | 3011 | 9256;9257;9258 | chr2:178768805;178768804;178768803 | chr2:179633532;179633531;179633530 |
| N2B | 2965 | 9118;9119;9120 | chr2:178768805;178768804;178768803 | chr2:179633532;179633531;179633530 |
| Novex-1 | 2965 | 9118;9119;9120 | chr2:178768805;178768804;178768803 | chr2:179633532;179633531;179633530 |
| Novex-2 | 2965 | 9118;9119;9120 | chr2:178768805;178768804;178768803 | chr2:179633532;179633531;179633530 |
| Novex-3 | 3011 | 9256;9257;9258 | chr2:178768805;178768804;178768803 | chr2:179633532;179633531;179633530 |
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/I | rs753265092  |
-0.079 | 0.994 | N | 0.412 | 0.391 | 0.267299060538 | gnomAD-2.1.1 | 7.96E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.76E-05 | 0 |
| T/I | rs753265092 |
-0.079 | 0.994 | N | 0.412 | 0.391 | 0.267299060538 | gnomAD-4.0.0 | 3.18122E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.71298E-06 | 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 | 0.2284 | likely_benign | 0.1732 | benign | -0.357 | Destabilizing | 0.835 | D | 0.336 | neutral | N | 0.44987225 | None | None | N |
| T/C | 0.8009 | likely_pathogenic | 0.7952 | pathogenic | -0.111 | Destabilizing | 1.0 | D | 0.424 | neutral | None | None | None | None | N |
| T/D | 0.6235 | likely_pathogenic | 0.5957 | pathogenic | -0.007 | Destabilizing | 0.97 | D | 0.386 | neutral | None | None | None | None | N |
| T/E | 0.8049 | likely_pathogenic | 0.7481 | pathogenic | -0.095 | Destabilizing | 0.97 | D | 0.395 | neutral | None | None | None | None | N |
| T/F | 0.808 | likely_pathogenic | 0.7364 | pathogenic | -0.896 | Destabilizing | 0.999 | D | 0.545 | neutral | None | None | None | None | N |
| T/G | 0.3444 | ambiguous | 0.3245 | benign | -0.473 | Destabilizing | 0.97 | D | 0.443 | neutral | None | None | None | None | N |
| T/H | 0.6427 | likely_pathogenic | 0.6163 | pathogenic | -0.811 | Destabilizing | 1.0 | D | 0.529 | neutral | None | None | None | None | N |
| T/I | 0.8269 | likely_pathogenic | 0.7186 | pathogenic | -0.171 | Destabilizing | 0.994 | D | 0.412 | neutral | N | 0.44232028 | None | None | N |
| T/K | 0.6798 | likely_pathogenic | 0.634 | pathogenic | -0.351 | Destabilizing | 0.97 | D | 0.386 | neutral | None | None | None | None | N |
| T/L | 0.4616 | ambiguous | 0.3595 | ambiguous | -0.171 | Destabilizing | 0.985 | D | 0.368 | neutral | None | None | None | None | N |
| T/M | 0.2875 | likely_benign | 0.2241 | benign | 0.148 | Stabilizing | 1.0 | D | 0.405 | neutral | None | None | None | None | N |
| T/N | 0.2132 | likely_benign | 0.1948 | benign | -0.068 | Destabilizing | 0.961 | D | 0.4 | neutral | N | 0.424050918 | None | None | N |
| T/P | 0.6344 | likely_pathogenic | 0.5488 | ambiguous | -0.206 | Destabilizing | 0.994 | D | 0.412 | neutral | N | 0.440138462 | None | None | N |
| T/Q | 0.6532 | likely_pathogenic | 0.6042 | pathogenic | -0.35 | Destabilizing | 0.996 | D | 0.388 | neutral | None | None | None | None | N |
| T/R | 0.6045 | likely_pathogenic | 0.5496 | ambiguous | -0.045 | Destabilizing | 0.996 | D | 0.405 | neutral | None | None | None | None | N |
| T/S | 0.1297 | likely_benign | 0.1225 | benign | -0.258 | Destabilizing | 0.287 | N | 0.168 | neutral | N | 0.375402238 | None | None | N |
| T/V | 0.6414 | likely_pathogenic | 0.5056 | ambiguous | -0.206 | Destabilizing | 0.985 | D | 0.362 | neutral | None | None | None | None | N |
| T/W | 0.9311 | likely_pathogenic | 0.9128 | pathogenic | -0.903 | Destabilizing | 1.0 | D | 0.604 | neutral | None | None | None | None | N |
| T/Y | 0.8307 | likely_pathogenic | 0.7889 | pathogenic | -0.622 | Destabilizing | 0.999 | D | 0.543 | 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.