Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32721 | 98386;98387;98388 | chr2:178539904;178539903;178539902 | chr2:179404631;179404630;179404629 |
| N2AB | 31080 | 93463;93464;93465 | chr2:178539904;178539903;178539902 | chr2:179404631;179404630;179404629 |
| N2A | 30153 | 90682;90683;90684 | chr2:178539904;178539903;178539902 | chr2:179404631;179404630;179404629 |
| N2B | 23656 | 71191;71192;71193 | chr2:178539904;178539903;178539902 | chr2:179404631;179404630;179404629 |
| Novex-1 | 23781 | 71566;71567;71568 | chr2:178539904;178539903;178539902 | chr2:179404631;179404630;179404629 |
| Novex-2 | 23848 | 71767;71768;71769 | chr2:178539904;178539903;178539902 | chr2:179404631;179404630;179404629 |
| 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 | rs533651182  |
-0.088 | 0.973 | N | 0.501 | 0.2 | None | gnomAD-2.1.1 | 3.62E-05 | None | None | None | None | I | None | 6.46E-05 | 0 | None | 9.95E-05 | 1.11321E-04 | None | 6.54E-05 | None | 0 | 2.67E-05 | 0 |
| V/I | rs533651182 |
-0.088 | 0.973 | N | 0.501 | 0.2 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 1.92753E-04 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs533651182 |
-0.088 | 0.973 | N | 0.501 | 0.2 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| V/I | rs533651182 |
-0.088 | 0.973 | N | 0.501 | 0.2 | None | gnomAD-4.0.0 | 1.98298E-05 | None | None | None | None | I | None | 2.66674E-05 | 0 | None | 3.37815E-05 | 4.45752E-05 | None | 0 | 3.30142E-04 | 1.94955E-05 | 2.19587E-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 | 0.406 | ambiguous | 0.3323 | benign | -1.029 | Destabilizing | 0.02 | N | 0.265 | neutral | N | 0.447087558 | None | None | I |
| V/C | 0.872 | likely_pathogenic | 0.8204 | pathogenic | -0.882 | Destabilizing | 0.999 | D | 0.528 | neutral | None | None | None | None | I |
| V/D | 0.7605 | likely_pathogenic | 0.6883 | pathogenic | -0.579 | Destabilizing | 0.991 | D | 0.659 | neutral | N | 0.432155391 | None | None | I |
| V/E | 0.7096 | likely_pathogenic | 0.6317 | pathogenic | -0.616 | Destabilizing | 0.986 | D | 0.555 | neutral | None | None | None | None | I |
| V/F | 0.3995 | ambiguous | 0.3267 | benign | -0.801 | Destabilizing | 0.999 | D | 0.525 | neutral | N | 0.456653166 | None | None | I |
| V/G | 0.532 | ambiguous | 0.461 | ambiguous | -1.288 | Destabilizing | 0.885 | D | 0.531 | neutral | N | 0.494302715 | None | None | I |
| V/H | 0.9053 | likely_pathogenic | 0.8572 | pathogenic | -0.706 | Destabilizing | 0.999 | D | 0.643 | neutral | None | None | None | None | I |
| V/I | 0.1053 | likely_benign | 0.0933 | benign | -0.45 | Destabilizing | 0.973 | D | 0.501 | neutral | N | 0.494649432 | None | None | I |
| V/K | 0.8363 | likely_pathogenic | 0.7735 | pathogenic | -0.894 | Destabilizing | 0.986 | D | 0.577 | neutral | None | None | None | None | I |
| V/L | 0.4924 | ambiguous | 0.406 | ambiguous | -0.45 | Destabilizing | 0.941 | D | 0.51 | neutral | N | 0.494302715 | None | None | I |
| V/M | 0.2919 | likely_benign | 0.2327 | benign | -0.457 | Destabilizing | 0.998 | D | 0.51 | neutral | None | None | None | None | I |
| V/N | 0.5882 | likely_pathogenic | 0.4928 | ambiguous | -0.695 | Destabilizing | 0.993 | D | 0.675 | neutral | None | None | None | None | I |
| V/P | 0.8947 | likely_pathogenic | 0.8427 | pathogenic | -0.606 | Destabilizing | 0.993 | D | 0.604 | neutral | None | None | None | None | I |
| V/Q | 0.7412 | likely_pathogenic | 0.6662 | pathogenic | -0.873 | Destabilizing | 0.993 | D | 0.612 | neutral | None | None | None | None | I |
| V/R | 0.7952 | likely_pathogenic | 0.7415 | pathogenic | -0.362 | Destabilizing | 0.993 | D | 0.673 | neutral | None | None | None | None | I |
| V/S | 0.4589 | ambiguous | 0.3924 | ambiguous | -1.208 | Destabilizing | 0.91 | D | 0.467 | neutral | None | None | None | None | I |
| V/T | 0.3742 | ambiguous | 0.3063 | benign | -1.132 | Destabilizing | 0.953 | D | 0.461 | neutral | None | None | None | None | I |
| V/W | 0.9593 | likely_pathogenic | 0.9312 | pathogenic | -0.916 | Destabilizing | 0.999 | D | 0.679 | prob.neutral | None | None | None | None | I |
| V/Y | 0.8292 | likely_pathogenic | 0.7521 | pathogenic | -0.633 | Destabilizing | 0.998 | D | 0.537 | 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.