Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33280 | 100063;100064;100065 | chr2:178537369;178537368;178537367 | chr2:179402096;179402095;179402094 |
| N2AB | 31639 | 95140;95141;95142 | chr2:178537369;178537368;178537367 | chr2:179402096;179402095;179402094 |
| N2A | 30712 | 92359;92360;92361 | chr2:178537369;178537368;178537367 | chr2:179402096;179402095;179402094 |
| N2B | 24215 | 72868;72869;72870 | chr2:178537369;178537368;178537367 | chr2:179402096;179402095;179402094 |
| Novex-1 | 24340 | 73243;73244;73245 | chr2:178537369;178537368;178537367 | chr2:179402096;179402095;179402094 |
| Novex-2 | 24407 | 73444;73445;73446 | chr2:178537369;178537368;178537367 | chr2:179402096;179402095;179402094 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs375178211  |
-0.291 | 0.292 | N | 0.381 | 0.058 | 0.238705975628 | gnomAD-2.1.1 | 4.29E-06 | None | None | None | None | I | None | 6.66E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/E | rs375178211 |
-0.291 | 0.292 | N | 0.381 | 0.058 | 0.238705975628 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/E | rs375178211 |
-0.291 | 0.292 | N | 0.381 | 0.058 | 0.238705975628 | gnomAD-4.0.0 | 6.56996E-06 | None | None | None | None | I | None | 2.41208E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/H | rs748316295 |
0.287 | 1.0 | N | 0.737 | 0.444 | None | gnomAD-2.1.1 | 4.27E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.68E-05 | None | 0 | 0 | 0 |
| D/H | rs748316295 |
0.287 | 1.0 | N | 0.737 | 0.444 | None | gnomAD-4.0.0 | 4.87148E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.55319E-06 | 1.22342E-05 | 1.68833E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.4175 | ambiguous | 0.3465 | ambiguous | -0.299 | Destabilizing | 0.999 | D | 0.718 | prob.delet. | N | 0.47333645 | None | None | I |
| D/C | 0.8846 | likely_pathogenic | 0.8456 | pathogenic | -0.161 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | I |
| D/E | 0.3398 | likely_benign | 0.2701 | benign | -0.464 | Destabilizing | 0.292 | N | 0.381 | neutral | N | 0.430273532 | None | None | I |
| D/F | 0.8823 | likely_pathogenic | 0.8595 | pathogenic | -0.085 | Destabilizing | 1.0 | D | 0.782 | deleterious | None | None | None | None | I |
| D/G | 0.4509 | ambiguous | 0.3903 | ambiguous | -0.554 | Destabilizing | 0.998 | D | 0.713 | prob.delet. | N | 0.485246955 | None | None | I |
| D/H | 0.5783 | likely_pathogenic | 0.4753 | ambiguous | -0.101 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | N | 0.466391835 | None | None | I |
| D/I | 0.7819 | likely_pathogenic | 0.7236 | pathogenic | 0.339 | Stabilizing | 1.0 | D | 0.804 | deleterious | None | None | None | None | I |
| D/K | 0.751 | likely_pathogenic | 0.6459 | pathogenic | -0.034 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | I |
| D/L | 0.7628 | likely_pathogenic | 0.7209 | pathogenic | 0.339 | Stabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | I |
| D/M | 0.8926 | likely_pathogenic | 0.8599 | pathogenic | 0.439 | Stabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | I |
| D/N | 0.2008 | likely_benign | 0.1676 | benign | -0.354 | Destabilizing | 0.999 | D | 0.711 | prob.delet. | N | 0.434087415 | None | None | I |
| D/P | 0.9441 | likely_pathogenic | 0.9266 | pathogenic | 0.15 | Stabilizing | 0.998 | D | 0.761 | deleterious | None | None | None | None | I |
| D/Q | 0.692 | likely_pathogenic | 0.6002 | pathogenic | -0.287 | Destabilizing | 0.999 | D | 0.745 | deleterious | None | None | None | None | I |
| D/R | 0.8011 | likely_pathogenic | 0.7225 | pathogenic | 0.191 | Stabilizing | 1.0 | D | 0.78 | deleterious | None | None | None | None | I |
| D/S | 0.2643 | likely_benign | 0.2073 | benign | -0.497 | Destabilizing | 0.997 | D | 0.657 | neutral | None | None | None | None | I |
| D/T | 0.4717 | ambiguous | 0.4013 | ambiguous | -0.303 | Destabilizing | 0.999 | D | 0.769 | deleterious | None | None | None | None | I |
| D/V | 0.5473 | ambiguous | 0.486 | ambiguous | 0.15 | Stabilizing | 0.999 | D | 0.776 | deleterious | N | 0.466391835 | None | None | I |
| D/W | 0.9755 | likely_pathogenic | 0.9665 | pathogenic | 0.054 | Stabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | I |
| D/Y | 0.5567 | ambiguous | 0.4882 | ambiguous | 0.14 | Stabilizing | 1.0 | D | 0.781 | deleterious | N | 0.460812657 | 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.