Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 34328 | 103207;103208;103209 | chr2:178533633;178533632;178533631 | chr2:179398360;179398359;179398358 |
| N2AB | 32687 | 98284;98285;98286 | chr2:178533633;178533632;178533631 | chr2:179398360;179398359;179398358 |
| N2A | 31760 | 95503;95504;95505 | chr2:178533633;178533632;178533631 | chr2:179398360;179398359;179398358 |
| N2B | 25263 | 76012;76013;76014 | chr2:178533633;178533632;178533631 | chr2:179398360;179398359;179398358 |
| Novex-1 | 25388 | 76387;76388;76389 | chr2:178533633;178533632;178533631 | chr2:179398360;179398359;179398358 |
| Novex-2 | 25455 | 76588;76589;76590 | chr2:178533633;178533632;178533631 | chr2:179398360;179398359;179398358 |
| 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 | rs541125667  |
-0.732 | 0.008 | N | 0.251 | 0.033 | 0.0551355673512 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.86E-06 | 0 |
| D/E | rs541125667 |
-0.732 | 0.008 | N | 0.251 | 0.033 | 0.0551355673512 | gnomAD-4.0.0 | 2.0525E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69823E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1166 | likely_benign | 0.3154 | benign | -0.556 | Destabilizing | 0.003 | N | 0.375 | neutral | N | 0.409803315 | None | None | N |
| D/C | 0.6744 | likely_pathogenic | 0.856 | pathogenic | -0.14 | Destabilizing | 0.973 | D | 0.735 | prob.delet. | None | None | None | None | N |
| D/E | 0.2393 | likely_benign | 0.4466 | ambiguous | -0.832 | Destabilizing | 0.008 | N | 0.251 | neutral | N | 0.386966527 | None | None | N |
| D/F | 0.7093 | likely_pathogenic | 0.908 | pathogenic | -0.517 | Destabilizing | 0.906 | D | 0.741 | deleterious | None | None | None | None | N |
| D/G | 0.2189 | likely_benign | 0.3929 | ambiguous | -0.855 | Destabilizing | 0.338 | N | 0.57 | neutral | N | 0.447767057 | None | None | N |
| D/H | 0.3873 | ambiguous | 0.6445 | pathogenic | -0.821 | Destabilizing | 0.965 | D | 0.656 | neutral | N | 0.435479085 | None | None | N |
| D/I | 0.4857 | ambiguous | 0.7937 | pathogenic | 0.217 | Stabilizing | 0.826 | D | 0.737 | prob.delet. | None | None | None | None | N |
| D/K | 0.5289 | ambiguous | 0.7937 | pathogenic | -0.339 | Destabilizing | 0.404 | N | 0.603 | neutral | None | None | None | None | N |
| D/L | 0.5184 | ambiguous | 0.8011 | pathogenic | 0.217 | Stabilizing | 0.404 | N | 0.668 | neutral | None | None | None | None | N |
| D/M | 0.6766 | likely_pathogenic | 0.8976 | pathogenic | 0.7 | Stabilizing | 0.973 | D | 0.731 | prob.delet. | None | None | None | None | N |
| D/N | 0.0942 | likely_benign | 0.1334 | benign | -0.668 | Destabilizing | 0.505 | D | 0.519 | neutral | N | 0.472182712 | None | None | N |
| D/P | 0.8868 | likely_pathogenic | 0.9684 | pathogenic | -0.016 | Destabilizing | 0.906 | D | 0.677 | prob.neutral | None | None | None | None | N |
| D/Q | 0.4446 | ambiguous | 0.7176 | pathogenic | -0.59 | Destabilizing | 0.704 | D | 0.541 | neutral | None | None | None | None | N |
| D/R | 0.5569 | ambiguous | 0.8004 | pathogenic | -0.252 | Destabilizing | 0.826 | D | 0.714 | prob.delet. | None | None | None | None | N |
| D/S | 0.1075 | likely_benign | 0.1991 | benign | -0.873 | Destabilizing | 0.404 | N | 0.48 | neutral | None | None | None | None | N |
| D/T | 0.2652 | likely_benign | 0.5404 | ambiguous | -0.638 | Destabilizing | 0.04 | N | 0.321 | neutral | None | None | None | None | N |
| D/V | 0.3106 | likely_benign | 0.6362 | pathogenic | -0.016 | Destabilizing | 0.338 | N | 0.666 | neutral | N | 0.477743247 | None | None | N |
| D/W | 0.9469 | likely_pathogenic | 0.9855 | pathogenic | -0.426 | Destabilizing | 0.991 | D | 0.727 | prob.delet. | None | None | None | None | N |
| D/Y | 0.3217 | likely_benign | 0.5735 | pathogenic | -0.302 | Destabilizing | 0.957 | D | 0.739 | prob.delet. | N | 0.443530482 | 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.