Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15305 | 46138;46139;46140 | chr2:178620608;178620607;178620606 | chr2:179485335;179485334;179485333 |
| N2AB | 13664 | 41215;41216;41217 | chr2:178620608;178620607;178620606 | chr2:179485335;179485334;179485333 |
| N2A | 12737 | 38434;38435;38436 | chr2:178620608;178620607;178620606 | chr2:179485335;179485334;179485333 |
| N2B | 6240 | 18943;18944;18945 | chr2:178620608;178620607;178620606 | chr2:179485335;179485334;179485333 |
| Novex-1 | 6365 | 19318;19319;19320 | chr2:178620608;178620607;178620606 | chr2:179485335;179485334;179485333 |
| Novex-2 | 6432 | 19519;19520;19521 | chr2:178620608;178620607;178620606 | chr2:179485335;179485334;179485333 |
| 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/A | rs1281172313  |
-1.308 | 0.027 | N | 0.289 | 0.175 | 0.435371449458 | gnomAD-2.1.1 | 4.09E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.69E-05 | None | 0 | None | 0 | 0 | 0 |
| V/A | rs1281172313 |
-1.308 | 0.027 | N | 0.289 | 0.175 | 0.435371449458 | gnomAD-4.0.0 | 3.20302E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.79236E-05 | None | 0 | 0 | 0 | 1.44818E-05 | 0 |
| V/F | None | None | 0.317 | N | 0.42 | 0.128 | 0.231873229951 | gnomAD-4.0.0 | 1.60184E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.87171E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.281 | likely_benign | 0.1803 | benign | -1.3 | Destabilizing | 0.027 | N | 0.289 | neutral | N | 0.477426591 | None | None | N |
| V/C | 0.8041 | likely_pathogenic | 0.7277 | pathogenic | -0.8 | Destabilizing | 0.935 | D | 0.371 | neutral | None | None | None | None | N |
| V/D | 0.6261 | likely_pathogenic | 0.4295 | ambiguous | -1.414 | Destabilizing | 0.317 | N | 0.437 | neutral | D | 0.541815626 | None | None | N |
| V/E | 0.3956 | ambiguous | 0.3009 | benign | -1.461 | Destabilizing | 0.38 | N | 0.404 | neutral | None | None | None | None | N |
| V/F | 0.3122 | likely_benign | 0.177 | benign | -1.098 | Destabilizing | 0.317 | N | 0.42 | neutral | N | 0.479707679 | None | None | N |
| V/G | 0.4756 | ambiguous | 0.3241 | benign | -1.55 | Destabilizing | 0.317 | N | 0.405 | neutral | D | 0.546956627 | None | None | N |
| V/H | 0.7354 | likely_pathogenic | 0.5724 | pathogenic | -1.092 | Destabilizing | 0.935 | D | 0.414 | neutral | None | None | None | None | N |
| V/I | 0.0812 | likely_benign | 0.0617 | benign | -0.731 | Destabilizing | None | N | 0.093 | neutral | N | 0.440992144 | None | None | N |
| V/K | 0.4874 | ambiguous | 0.3284 | benign | -1.312 | Destabilizing | 0.38 | N | 0.403 | neutral | None | None | None | None | N |
| V/L | 0.1967 | likely_benign | 0.1228 | benign | -0.731 | Destabilizing | None | N | 0.089 | neutral | N | 0.44591091 | None | None | N |
| V/M | 0.189 | likely_benign | 0.1281 | benign | -0.511 | Destabilizing | 0.38 | N | 0.43 | neutral | None | None | None | None | N |
| V/N | 0.5231 | ambiguous | 0.3087 | benign | -1.028 | Destabilizing | 0.38 | N | 0.445 | neutral | None | None | None | None | N |
| V/P | 0.8794 | likely_pathogenic | 0.7315 | pathogenic | -0.887 | Destabilizing | 0.555 | D | 0.429 | neutral | None | None | None | None | N |
| V/Q | 0.4574 | ambiguous | 0.3366 | benign | -1.265 | Destabilizing | 0.555 | D | 0.38 | neutral | None | None | None | None | N |
| V/R | 0.4163 | ambiguous | 0.2652 | benign | -0.655 | Destabilizing | 0.38 | N | 0.431 | neutral | None | None | None | None | N |
| V/S | 0.3843 | ambiguous | 0.2292 | benign | -1.4 | Destabilizing | 0.081 | N | 0.346 | neutral | None | None | None | None | N |
| V/T | 0.2015 | likely_benign | 0.1342 | benign | -1.357 | Destabilizing | 0.001 | N | 0.181 | neutral | None | None | None | None | N |
| V/W | 0.866 | likely_pathogenic | 0.748 | pathogenic | -1.258 | Destabilizing | 0.935 | D | 0.562 | neutral | None | None | None | None | N |
| V/Y | 0.7048 | likely_pathogenic | 0.5278 | ambiguous | -1.012 | Destabilizing | 0.555 | D | 0.424 | 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.