Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20218 | 60877;60878;60879 | chr2:178591073;178591072;178591071 | chr2:179455800;179455799;179455798 |
| N2AB | 18577 | 55954;55955;55956 | chr2:178591073;178591072;178591071 | chr2:179455800;179455799;179455798 |
| N2A | 17650 | 53173;53174;53175 | chr2:178591073;178591072;178591071 | chr2:179455800;179455799;179455798 |
| N2B | 11153 | 33682;33683;33684 | chr2:178591073;178591072;178591071 | chr2:179455800;179455799;179455798 |
| Novex-1 | 11278 | 34057;34058;34059 | chr2:178591073;178591072;178591071 | chr2:179455800;179455799;179455798 |
| Novex-2 | 11345 | 34258;34259;34260 | chr2:178591073;178591072;178591071 | chr2:179455800;179455799;179455798 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs766630391  |
-0.275 | 0.489 | N | 0.401 | 0.095 | 0.19670166235 | gnomAD-2.1.1 | 2.42E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 5.36E-05 | 0 |
| T/A | rs766630391 |
-0.275 | 0.489 | N | 0.401 | 0.095 | 0.19670166235 | gnomAD-4.0.0 | 8.89675E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.16949E-05 | 0 | 0 |
| T/K | rs375155937 |
None | 0.954 | N | 0.377 | 0.347 | None | gnomAD-4.0.0 | 1.36875E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79923E-06 | 0 | 0 |
| T/M | rs375155937 |
-0.061 | 1.0 | N | 0.437 | 0.328 | None | gnomAD-2.1.1 | 2.51E-05 | None | None | None | None | I | None | 8.27E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.92E-05 | 0 |
| T/M | rs375155937 |
-0.061 | 1.0 | N | 0.437 | 0.328 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| T/M | rs375155937 |
-0.061 | 1.0 | N | 0.437 | 0.328 | None | gnomAD-4.0.0 | 9.29821E-06 | None | None | None | None | I | None | 2.67151E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.01732E-05 | 0 | 1.60154E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0758 | likely_benign | 0.0788 | benign | -0.412 | Destabilizing | 0.489 | N | 0.401 | neutral | N | 0.490081479 | None | None | I |
| T/C | 0.3213 | likely_benign | 0.2997 | benign | -0.252 | Destabilizing | 0.998 | D | 0.466 | neutral | None | None | None | None | I |
| T/D | 0.3665 | ambiguous | 0.4081 | ambiguous | 0.15 | Stabilizing | 0.956 | D | 0.378 | neutral | None | None | None | None | I |
| T/E | 0.3029 | likely_benign | 0.3305 | benign | 0.079 | Stabilizing | 0.86 | D | 0.361 | neutral | None | None | None | None | I |
| T/F | 0.2301 | likely_benign | 0.2413 | benign | -0.848 | Destabilizing | 0.978 | D | 0.554 | neutral | None | None | None | None | I |
| T/G | 0.2061 | likely_benign | 0.2059 | benign | -0.553 | Destabilizing | 0.754 | D | 0.446 | neutral | None | None | None | None | I |
| T/H | 0.2192 | likely_benign | 0.2195 | benign | -0.763 | Destabilizing | 0.092 | N | 0.424 | neutral | None | None | None | None | I |
| T/I | 0.1259 | likely_benign | 0.1299 | benign | -0.159 | Destabilizing | 0.978 | D | 0.431 | neutral | None | None | None | None | I |
| T/K | 0.1848 | likely_benign | 0.1937 | benign | -0.411 | Destabilizing | 0.954 | D | 0.377 | neutral | N | 0.460740007 | None | None | I |
| T/L | 0.1015 | likely_benign | 0.105 | benign | -0.159 | Destabilizing | 0.86 | D | 0.372 | neutral | None | None | None | None | I |
| T/M | 0.0996 | likely_benign | 0.1037 | benign | -0.053 | Destabilizing | 1.0 | D | 0.437 | neutral | N | 0.504224212 | None | None | I |
| T/N | 0.1147 | likely_benign | 0.1229 | benign | -0.127 | Destabilizing | 0.754 | D | 0.328 | neutral | None | None | None | None | I |
| T/P | 0.148 | likely_benign | 0.1451 | benign | -0.215 | Destabilizing | 0.971 | D | 0.429 | neutral | N | 0.476864253 | None | None | I |
| T/Q | 0.2148 | likely_benign | 0.219 | benign | -0.348 | Destabilizing | 0.956 | D | 0.415 | neutral | None | None | None | None | I |
| T/R | 0.1608 | likely_benign | 0.1688 | benign | -0.1 | Destabilizing | 0.976 | D | 0.431 | neutral | N | 0.48280879 | None | None | I |
| T/S | 0.1036 | likely_benign | 0.1048 | benign | -0.351 | Destabilizing | 0.058 | N | 0.283 | neutral | N | 0.481883283 | None | None | I |
| T/V | 0.1101 | likely_benign | 0.1096 | benign | -0.215 | Destabilizing | 0.86 | D | 0.335 | neutral | None | None | None | None | I |
| T/W | 0.5783 | likely_pathogenic | 0.5884 | pathogenic | -0.854 | Destabilizing | 0.998 | D | 0.625 | neutral | None | None | None | None | I |
| T/Y | 0.2614 | likely_benign | 0.2574 | benign | -0.585 | Destabilizing | 0.956 | D | 0.539 | 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.