Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 4711 | 14356;14357;14358 | chr2:178738322;178738321;178738320 | chr2:179603049;179603048;179603047 |
| N2AB | 4394 | 13405;13406;13407 | chr2:178738322;178738321;178738320 | chr2:179603049;179603048;179603047 |
| N2A | 3467 | 10624;10625;10626 | chr2:178738322;178738321;178738320 | chr2:179603049;179603048;179603047 |
| N2B | 4348 | 13267;13268;13269 | chr2:178738322;178738321;178738320 | chr2:179603049;179603048;179603047 |
| Novex-1 | 4473 | 13642;13643;13644 | chr2:178738322;178738321;178738320 | chr2:179603049;179603048;179603047 |
| Novex-2 | 4540 | 13843;13844;13845 | chr2:178738322;178738321;178738320 | chr2:179603049;179603048;179603047 |
| 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 | rs1217292413  |
-1.427 | 0.994 | N | 0.447 | 0.519 | 0.583333579207 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 2.91E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/A | rs1217292413 |
-1.427 | 0.994 | N | 0.447 | 0.519 | 0.583333579207 | gnomAD-4.0.0 | 6.84448E-07 | None | None | None | None | I | None | 0 | 2.23734E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/E | None | None | 0.999 | D | 0.713 | 0.774 | 0.800342540491 | gnomAD-4.0.0 | 1.3689E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79932E-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 | 0.4141 | ambiguous | 0.4199 | ambiguous | -1.729 | Destabilizing | 0.994 | D | 0.447 | neutral | N | 0.517742782 | None | None | I |
| V/C | 0.9525 | likely_pathogenic | 0.9502 | pathogenic | -1.272 | Destabilizing | 1.0 | D | 0.662 | neutral | None | None | None | None | I |
| V/D | 0.9264 | likely_pathogenic | 0.9359 | pathogenic | -2.161 | Highly Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | I |
| V/E | 0.824 | likely_pathogenic | 0.8576 | pathogenic | -2.132 | Highly Destabilizing | 0.999 | D | 0.713 | prob.delet. | D | 0.584810178 | None | None | I |
| V/F | 0.6733 | likely_pathogenic | 0.7387 | pathogenic | -1.384 | Destabilizing | 0.999 | D | 0.73 | prob.delet. | None | None | None | None | I |
| V/G | 0.5944 | likely_pathogenic | 0.6268 | pathogenic | -2.076 | Highly Destabilizing | 0.999 | D | 0.745 | deleterious | D | 0.575731579 | None | None | I |
| V/H | 0.9714 | likely_pathogenic | 0.9782 | pathogenic | -1.693 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | I |
| V/I | 0.1519 | likely_benign | 0.1626 | benign | -0.844 | Destabilizing | 0.543 | D | 0.251 | neutral | N | 0.51318696 | None | None | I |
| V/K | 0.9011 | likely_pathogenic | 0.9159 | pathogenic | -1.348 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | I |
| V/L | 0.7342 | likely_pathogenic | 0.7866 | pathogenic | -0.844 | Destabilizing | 0.948 | D | 0.393 | neutral | D | 0.523791453 | None | None | I |
| V/M | 0.5079 | ambiguous | 0.5603 | ambiguous | -0.68 | Destabilizing | 0.999 | D | 0.734 | prob.delet. | None | None | None | None | I |
| V/N | 0.8615 | likely_pathogenic | 0.8819 | pathogenic | -1.264 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | I |
| V/P | 0.981 | likely_pathogenic | 0.989 | pathogenic | -1.108 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | I |
| V/Q | 0.8822 | likely_pathogenic | 0.9114 | pathogenic | -1.435 | Destabilizing | 1.0 | D | 0.708 | prob.delet. | None | None | None | None | I |
| V/R | 0.884 | likely_pathogenic | 0.8978 | pathogenic | -0.881 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | I |
| V/S | 0.6906 | likely_pathogenic | 0.699 | pathogenic | -1.753 | Destabilizing | 1.0 | D | 0.726 | prob.delet. | None | None | None | None | I |
| V/T | 0.3729 | ambiguous | 0.3822 | ambiguous | -1.62 | Destabilizing | 0.996 | D | 0.665 | neutral | None | None | None | None | I |
| V/W | 0.9902 | likely_pathogenic | 0.9934 | pathogenic | -1.661 | Destabilizing | 1.0 | D | 0.662 | neutral | None | None | None | None | I |
| V/Y | 0.9441 | likely_pathogenic | 0.9546 | pathogenic | -1.346 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | 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.