Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14411 | 43456;43457;43458 | chr2:178632775;178632774;178632773 | chr2:179497502;179497501;179497500 |
| N2AB | 12770 | 38533;38534;38535 | chr2:178632775;178632774;178632773 | chr2:179497502;179497501;179497500 |
| N2A | 11843 | 35752;35753;35754 | chr2:178632775;178632774;178632773 | chr2:179497502;179497501;179497500 |
| N2B | 5346 | 16261;16262;16263 | chr2:178632775;178632774;178632773 | chr2:179497502;179497501;179497500 |
| Novex-1 | 5471 | 16636;16637;16638 | chr2:178632775;178632774;178632773 | chr2:179497502;179497501;179497500 |
| Novex-2 | 5538 | 16837;16838;16839 | chr2:178632775;178632774;178632773 | chr2:179497502;179497501;179497500 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/F | None | None | 0.989 | D | 0.473 | 0.486 | 0.750306904936 | gnomAD-4.0.0 | 6.84539E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99661E-07 | 0 | 0 |
| I/L | rs1246262420  |
-0.31 | 0.031 | N | 0.136 | 0.286 | 0.555712064712 | 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 |
| I/V | None | None | 0.248 | N | 0.142 | 0.274 | 0.648041160416 | gnomAD-4.0.0 | 5.47631E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.19729E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.6946 | likely_pathogenic | 0.6424 | pathogenic | -1.096 | Destabilizing | 0.97 | D | 0.475 | neutral | None | None | None | None | N |
| I/C | 0.8819 | likely_pathogenic | 0.8482 | pathogenic | -0.755 | Destabilizing | 1.0 | D | 0.553 | neutral | None | None | None | None | N |
| I/D | 0.9005 | likely_pathogenic | 0.8941 | pathogenic | -0.209 | Destabilizing | 0.999 | D | 0.633 | neutral | None | None | None | None | N |
| I/E | 0.7582 | likely_pathogenic | 0.7494 | pathogenic | -0.244 | Destabilizing | 0.999 | D | 0.636 | neutral | None | None | None | None | N |
| I/F | 0.3071 | likely_benign | 0.2634 | benign | -0.722 | Destabilizing | 0.989 | D | 0.473 | neutral | D | 0.545429141 | None | None | N |
| I/G | 0.8969 | likely_pathogenic | 0.8729 | pathogenic | -1.353 | Destabilizing | 0.999 | D | 0.623 | neutral | None | None | None | None | N |
| I/H | 0.6984 | likely_pathogenic | 0.6668 | pathogenic | -0.448 | Destabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | N |
| I/K | 0.4814 | ambiguous | 0.4871 | ambiguous | -0.63 | Destabilizing | 0.999 | D | 0.625 | neutral | None | None | None | None | N |
| I/L | 0.156 | likely_benign | 0.1293 | benign | -0.501 | Destabilizing | 0.031 | N | 0.136 | neutral | N | 0.477060738 | None | None | N |
| I/M | 0.1785 | likely_benign | 0.1584 | benign | -0.45 | Destabilizing | 0.989 | D | 0.517 | neutral | D | 0.547337054 | None | None | N |
| I/N | 0.5299 | ambiguous | 0.5211 | ambiguous | -0.455 | Destabilizing | 0.998 | D | 0.648 | neutral | D | 0.54534585 | None | None | N |
| I/P | 0.9252 | likely_pathogenic | 0.9071 | pathogenic | -0.666 | Destabilizing | 0.999 | D | 0.641 | neutral | None | None | None | None | N |
| I/Q | 0.6128 | likely_pathogenic | 0.5855 | pathogenic | -0.639 | Destabilizing | 0.999 | D | 0.648 | neutral | None | None | None | None | N |
| I/R | 0.3905 | ambiguous | 0.3755 | ambiguous | -0.049 | Destabilizing | 0.999 | D | 0.645 | neutral | None | None | None | None | N |
| I/S | 0.5736 | likely_pathogenic | 0.5583 | ambiguous | -1.071 | Destabilizing | 0.994 | D | 0.531 | neutral | D | 0.527739372 | None | None | N |
| I/T | 0.429 | ambiguous | 0.4121 | ambiguous | -0.991 | Destabilizing | 0.961 | D | 0.469 | neutral | N | 0.504091129 | None | None | N |
| I/V | 0.1275 | likely_benign | 0.1169 | benign | -0.666 | Destabilizing | 0.248 | N | 0.142 | neutral | N | 0.441395365 | None | None | N |
| I/W | 0.8947 | likely_pathogenic | 0.8668 | pathogenic | -0.729 | Destabilizing | 1.0 | D | 0.702 | prob.neutral | None | None | None | None | N |
| I/Y | 0.7085 | likely_pathogenic | 0.6801 | pathogenic | -0.51 | Destabilizing | 0.999 | D | 0.551 | 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.