Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19317 | 58174;58175;58176 | chr2:178594545;178594544;178594543 | chr2:179459272;179459271;179459270 |
| N2AB | 17676 | 53251;53252;53253 | chr2:178594545;178594544;178594543 | chr2:179459272;179459271;179459270 |
| N2A | 16749 | 50470;50471;50472 | chr2:178594545;178594544;178594543 | chr2:179459272;179459271;179459270 |
| N2B | 10252 | 30979;30980;30981 | chr2:178594545;178594544;178594543 | chr2:179459272;179459271;179459270 |
| Novex-1 | 10377 | 31354;31355;31356 | chr2:178594545;178594544;178594543 | chr2:179459272;179459271;179459270 |
| Novex-2 | 10444 | 31555;31556;31557 | chr2:178594545;178594544;178594543 | chr2:179459272;179459271;179459270 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/L | rs752651782  |
None | None | N | 0.093 | 0.153 | 0.356072328145 | 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 |
| I/L | rs752651782 |
None | None | N | 0.093 | 0.153 | 0.356072328145 | gnomAD-4.0.0 | 6.57246E-06 | None | None | None | None | I | None | 2.41138E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs1249290348 |
-1.191 | None | N | 0.147 | 0.152 | 0.475112344478 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| I/T | rs1249290348 |
-1.191 | None | N | 0.147 | 0.152 | 0.475112344478 | gnomAD-4.0.0 | 3.18466E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.77793E-05 | None | 0 | 0 | 2.86035E-06 | 0 | 0 |
| I/V | rs752651782 |
-1.003 | 0.019 | N | 0.169 | 0.115 | 0.506068822696 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs752651782 |
-1.003 | 0.019 | N | 0.169 | 0.115 | 0.506068822696 | gnomAD-4.0.0 | 1.59231E-06 | None | None | None | None | I | None | 0 | 2.28791E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.3272 | likely_benign | 0.292 | benign | -1.469 | Destabilizing | 0.025 | N | 0.203 | neutral | None | None | None | None | I |
| I/C | 0.6531 | likely_pathogenic | 0.6339 | pathogenic | -0.795 | Destabilizing | 0.859 | D | 0.304 | neutral | None | None | None | None | I |
| I/D | 0.7549 | likely_pathogenic | 0.6773 | pathogenic | -1.113 | Destabilizing | 0.055 | N | 0.285 | neutral | None | None | None | None | I |
| I/E | 0.4837 | ambiguous | 0.4163 | ambiguous | -1.148 | Destabilizing | 0.002 | N | 0.247 | neutral | None | None | None | None | I |
| I/F | 0.2726 | likely_benign | 0.2253 | benign | -1.091 | Destabilizing | 0.096 | N | 0.273 | neutral | N | 0.478356997 | None | None | I |
| I/G | 0.6211 | likely_pathogenic | 0.5695 | pathogenic | -1.747 | Destabilizing | 0.22 | N | 0.304 | neutral | None | None | None | None | I |
| I/H | 0.53 | ambiguous | 0.4464 | ambiguous | -0.921 | Destabilizing | 0.859 | D | 0.289 | neutral | None | None | None | None | I |
| I/K | 0.284 | likely_benign | 0.2216 | benign | -1.092 | Destabilizing | 0.104 | N | 0.286 | neutral | None | None | None | None | I |
| I/L | 0.1216 | likely_benign | 0.1143 | benign | -0.798 | Destabilizing | None | N | 0.093 | neutral | N | 0.425838 | None | None | I |
| I/M | 0.1001 | likely_benign | 0.0936 | benign | -0.541 | Destabilizing | 0.427 | N | 0.306 | neutral | N | 0.497412883 | None | None | I |
| I/N | 0.2909 | likely_benign | 0.2245 | benign | -0.861 | Destabilizing | 0.175 | N | 0.322 | neutral | N | 0.501837268 | None | None | I |
| I/P | 0.9437 | likely_pathogenic | 0.9373 | pathogenic | -0.99 | Destabilizing | 0.364 | N | 0.36 | neutral | None | None | None | None | I |
| I/Q | 0.3364 | likely_benign | 0.2825 | benign | -1.092 | Destabilizing | 0.22 | N | 0.351 | neutral | None | None | None | None | I |
| I/R | 0.2808 | likely_benign | 0.2199 | benign | -0.391 | Destabilizing | 0.22 | N | 0.367 | neutral | None | None | None | None | I |
| I/S | 0.2716 | likely_benign | 0.2193 | benign | -1.375 | Destabilizing | 0.042 | N | 0.297 | neutral | N | 0.438401865 | None | None | I |
| I/T | 0.1153 | likely_benign | 0.0964 | benign | -1.304 | Destabilizing | None | N | 0.147 | neutral | N | 0.366018905 | None | None | I |
| I/V | 0.078 | likely_benign | 0.0796 | benign | -0.99 | Destabilizing | 0.019 | N | 0.169 | neutral | N | 0.460662649 | None | None | I |
| I/W | 0.8516 | likely_pathogenic | 0.7987 | pathogenic | -1.142 | Destabilizing | 0.958 | D | 0.289 | neutral | None | None | None | None | I |
| I/Y | 0.641 | likely_pathogenic | 0.5539 | ambiguous | -0.944 | Destabilizing | 0.667 | D | 0.394 | 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.