Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15196 | 45811;45812;45813 | chr2:178621132;178621131;178621130 | chr2:179485859;179485858;179485857 |
| N2AB | 13555 | 40888;40889;40890 | chr2:178621132;178621131;178621130 | chr2:179485859;179485858;179485857 |
| N2A | 12628 | 38107;38108;38109 | chr2:178621132;178621131;178621130 | chr2:179485859;179485858;179485857 |
| N2B | 6131 | 18616;18617;18618 | chr2:178621132;178621131;178621130 | chr2:179485859;179485858;179485857 |
| Novex-1 | 6256 | 18991;18992;18993 | chr2:178621132;178621131;178621130 | chr2:179485859;179485858;179485857 |
| Novex-2 | 6323 | 19192;19193;19194 | chr2:178621132;178621131;178621130 | chr2:179485859;179485858;179485857 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/T | rs372872095  |
-0.784 | 0.214 | N | 0.195 | 0.089 | None | gnomAD-2.1.1 | 2.83E-05 | None | None | None | None | N | None | 1.295E-04 | 0 | None | 0 | 0 | None | 1.63688E-04 | None | 0 | 0 | 0 |
| A/T | rs372872095 |
-0.784 | 0.214 | N | 0.195 | 0.089 | None | gnomAD-3.1.2 | 1.98E-05 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 2.07039E-04 | 0 |
| A/T | rs372872095 |
-0.784 | 0.214 | N | 0.195 | 0.089 | None | gnomAD-4.0.0 | 1.67462E-05 | None | None | None | None | N | None | 1.33718E-05 | 1.67274E-05 | None | 0 | 0 | None | 0 | 0 | 9.32822E-06 | 1.4286E-04 | 1.60292E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.6941 | likely_pathogenic | 0.6392 | pathogenic | -0.662 | Destabilizing | 0.999 | D | 0.581 | neutral | None | None | None | None | N |
| A/D | 0.462 | ambiguous | 0.4865 | ambiguous | -0.839 | Destabilizing | 0.896 | D | 0.521 | neutral | N | 0.448352806 | None | None | N |
| A/E | 0.378 | ambiguous | 0.3898 | ambiguous | -0.917 | Destabilizing | 0.919 | D | 0.526 | neutral | None | None | None | None | N |
| A/F | 0.4674 | ambiguous | 0.5188 | ambiguous | -0.893 | Destabilizing | 0.996 | D | 0.568 | neutral | None | None | None | None | N |
| A/G | 0.2284 | likely_benign | 0.2341 | benign | -0.81 | Destabilizing | 0.64 | D | 0.53 | neutral | N | 0.450571937 | None | None | N |
| A/H | 0.631 | likely_pathogenic | 0.6627 | pathogenic | -0.939 | Destabilizing | 0.999 | D | 0.579 | neutral | None | None | None | None | N |
| A/I | 0.3273 | likely_benign | 0.3638 | ambiguous | -0.306 | Destabilizing | 0.976 | D | 0.557 | neutral | None | None | None | None | N |
| A/K | 0.645 | likely_pathogenic | 0.6735 | pathogenic | -1.021 | Destabilizing | 0.919 | D | 0.527 | neutral | None | None | None | None | N |
| A/L | 0.2699 | likely_benign | 0.2873 | benign | -0.306 | Destabilizing | 0.919 | D | 0.5 | neutral | None | None | None | None | N |
| A/M | 0.334 | likely_benign | 0.3515 | ambiguous | -0.309 | Destabilizing | 0.999 | D | 0.577 | neutral | None | None | None | None | N |
| A/N | 0.3179 | likely_benign | 0.3351 | benign | -0.672 | Destabilizing | 0.976 | D | 0.521 | neutral | None | None | None | None | N |
| A/P | 0.8087 | likely_pathogenic | 0.8238 | pathogenic | -0.373 | Destabilizing | 0.994 | D | 0.56 | neutral | D | 0.613019601 | None | None | N |
| A/Q | 0.4079 | ambiguous | 0.4287 | ambiguous | -0.873 | Destabilizing | 0.988 | D | 0.581 | neutral | None | None | None | None | N |
| A/R | 0.5841 | likely_pathogenic | 0.6264 | pathogenic | -0.608 | Destabilizing | 0.976 | D | 0.569 | neutral | None | None | None | None | N |
| A/S | 0.092 | likely_benign | 0.0903 | benign | -0.924 | Destabilizing | 0.11 | N | 0.193 | neutral | N | 0.45352163 | None | None | N |
| A/T | 0.0935 | likely_benign | 0.1076 | benign | -0.916 | Destabilizing | 0.214 | N | 0.195 | neutral | N | 0.454336827 | None | None | N |
| A/V | 0.1589 | likely_benign | 0.1731 | benign | -0.373 | Destabilizing | 0.896 | D | 0.531 | neutral | N | 0.451541197 | None | None | N |
| A/W | 0.8901 | likely_pathogenic | 0.9013 | pathogenic | -1.177 | Destabilizing | 0.999 | D | 0.617 | neutral | None | None | None | None | N |
| A/Y | 0.6746 | likely_pathogenic | 0.6992 | pathogenic | -0.789 | Destabilizing | 0.996 | D | 0.582 | 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.