Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3211 | 9856;9857;9858 | chr2:178766453;178766452;178766451 | chr2:179631180;179631179;179631178 |
| N2AB | 3211 | 9856;9857;9858 | chr2:178766453;178766452;178766451 | chr2:179631180;179631179;179631178 |
| N2A | 3211 | 9856;9857;9858 | chr2:178766453;178766452;178766451 | chr2:179631180;179631179;179631178 |
| N2B | 3165 | 9718;9719;9720 | chr2:178766453;178766452;178766451 | chr2:179631180;179631179;179631178 |
| Novex-1 | 3165 | 9718;9719;9720 | chr2:178766453;178766452;178766451 | chr2:179631180;179631179;179631178 |
| Novex-2 | 3165 | 9718;9719;9720 | chr2:178766453;178766452;178766451 | chr2:179631180;179631179;179631178 |
| Novex-3 | 3211 | 9856;9857;9858 | chr2:178766453;178766452;178766451 | chr2:179631180;179631179;179631178 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/I | rs761751013  |
0.207 | 0.241 | N | 0.366 | 0.352 | 0.57985626996 | gnomAD-2.1.1 | 1.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.64E-05 | 0 |
| R/I | rs761751013 |
0.207 | 0.241 | N | 0.366 | 0.352 | 0.57985626996 | gnomAD-4.0.0 | 3.181E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.71308E-06 | 0 | 0 |
| R/S | rs753709846 |
-0.703 | 0.061 | N | 0.245 | 0.3 | 0.18274738541 | gnomAD-2.1.1 | 1.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.64E-05 | 0 |
| R/S | rs753709846 |
-0.703 | 0.061 | N | 0.245 | 0.3 | 0.18274738541 | gnomAD-4.0.0 | 3.18101E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.71311E-06 | 0 | 0 |
| R/T | rs761751013 |
-0.378 | 0.002 | N | 0.141 | 0.311 | 0.387850303812 | gnomAD-2.1.1 | 1.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 1.76E-05 | 0 |
| R/T | rs761751013 |
-0.378 | 0.002 | N | 0.141 | 0.311 | 0.387850303812 | gnomAD-4.0.0 | 6.36199E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.56962E-06 | 1.43271E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.409 | ambiguous | 0.5061 | ambiguous | -0.407 | Destabilizing | 0.036 | N | 0.231 | neutral | None | None | None | None | N |
| R/C | 0.2389 | likely_benign | 0.2736 | benign | -0.278 | Destabilizing | 0.901 | D | 0.268 | neutral | None | None | None | None | N |
| R/D | 0.7301 | likely_pathogenic | 0.8109 | pathogenic | 0.025 | Stabilizing | 0.296 | N | 0.377 | neutral | None | None | None | None | N |
| R/E | 0.3649 | ambiguous | 0.4577 | ambiguous | 0.125 | Stabilizing | 0.08 | N | 0.195 | neutral | None | None | None | None | N |
| R/F | 0.5151 | ambiguous | 0.5825 | pathogenic | -0.384 | Destabilizing | 0.001 | N | 0.167 | neutral | None | None | None | None | N |
| R/G | 0.2843 | likely_benign | 0.3882 | ambiguous | -0.69 | Destabilizing | 0.116 | N | 0.257 | neutral | N | 0.508802964 | None | None | N |
| R/H | 0.134 | likely_benign | 0.1401 | benign | -1.107 | Destabilizing | 0.596 | D | 0.213 | neutral | None | None | None | None | N |
| R/I | 0.2541 | likely_benign | 0.3408 | ambiguous | 0.334 | Stabilizing | 0.241 | N | 0.366 | neutral | N | 0.506955764 | None | None | N |
| R/K | 0.1144 | likely_benign | 0.1356 | benign | -0.404 | Destabilizing | None | N | 0.125 | neutral | N | 0.475794998 | None | None | N |
| R/L | 0.2285 | likely_benign | 0.278 | benign | 0.334 | Stabilizing | 0.036 | N | 0.233 | neutral | None | None | None | None | N |
| R/M | 0.2616 | likely_benign | 0.3637 | ambiguous | 0.035 | Stabilizing | 0.901 | D | 0.241 | neutral | None | None | None | None | N |
| R/N | 0.5662 | likely_pathogenic | 0.6503 | pathogenic | 0.118 | Stabilizing | 0.296 | N | 0.19 | neutral | None | None | None | None | N |
| R/P | 0.9186 | likely_pathogenic | 0.9514 | pathogenic | 0.109 | Stabilizing | 0.46 | N | 0.351 | neutral | None | None | None | None | N |
| R/Q | 0.106 | likely_benign | 0.1175 | benign | -0.062 | Destabilizing | 0.174 | N | 0.243 | neutral | None | None | None | None | N |
| R/S | 0.4283 | ambiguous | 0.5256 | ambiguous | -0.513 | Destabilizing | 0.061 | N | 0.245 | neutral | N | 0.498560541 | None | None | N |
| R/T | 0.1986 | likely_benign | 0.2748 | benign | -0.245 | Destabilizing | 0.002 | N | 0.141 | neutral | N | 0.459563816 | None | None | N |
| R/V | 0.3272 | likely_benign | 0.3847 | ambiguous | 0.109 | Stabilizing | 0.08 | N | 0.289 | neutral | None | None | None | None | N |
| R/W | 0.198 | likely_benign | 0.2629 | benign | -0.175 | Destabilizing | 0.001 | N | 0.191 | neutral | None | None | None | None | N |
| R/Y | 0.4143 | ambiguous | 0.4618 | ambiguous | 0.166 | Stabilizing | None | N | 0.107 | 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.